Immunoglobulin A Deficiency



Selective immunoglobulin A deficiency (SIgAD) is a primary immunodeficiency disease and is the most common of the primary antibody deficiencies.[1] Total immunoglobulin A deficiency (IgAD) is defined as an undetectable serum immunoglobulin A (IgA) level at a value < 5 mg/dL (0.05 g/L) in humans. Partial IgAD refers to detectable but decreased IgA levels that are more than 2 standard deviations below normal age-adjusted means.[2, 3]

IgAD is commonly associated with normal B lymphocytes in peripheral blood, normal CD4+ and CD8+ T cells, and, usually, normal neutrophil and lymphocyte counts. Anti-IgA autoantibodies of the IgG and/or IgE isotype may be present. Peripheral blood may also be affected by autoimmune cytopenias, eg, autoimmune thrombocytopenia,[4, 5] and patients may have other autoimmune phenomena.

IgA was first identified by Graber and Williams in 1952; ten years later, the first patients with IgAD were described.

IgAD is a heterogeneous disorder, and the results of intensive study are beginning to elucidate genetic loci and molecular pathogenesis that contribute to various subtypes of this disorder. Several lines of evidence suggest that, in many cases, IgAD and common variable immunodeficiency (CVID) have a common pathogenesis, which is discussed further in Pathophysiology. Other data indicate different genetic risk factors. Family studies show variable inheritance patterns. Familial inheritance of IgAD occurs in approximately 20% of cases,[6] and, within families, IgAD and CVID are associated.[7, 8]

Many IgAD patients are asymptomatic (ie, "normal" blood donors) and are identified by finding a laboratory abnormality, without any apparent associated clinical disease. Some patients with IgAD may have the following associated conditions: (1) deficits in one or more immunoglobulin G (IgG) subclasses (this accounts for 20-30% of IgA-deficient patients, many of whom may have total IgG levels within the normal range) or (2) a deficient antibody response to pneumococcal immunization (specific polysaccharide antibody deficiency [SPAD]).

Some patients with IgAD later develop CVID, and family members of patients with CVID may have only selective IgAD. Characterization of the receptor for the transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), encoded by the gene TNFRSF13B ( tumor necrosis factor receptor superfamily member 13B), suggests that people with the C104, A181E, and ins204A variants may be at risk for IgAD that progresses to CVID.[9]

Primary IgAD is permanent, and below-normal levels have been noted to remain static and persist after 20 years of observation.[10] A recent report documents a rare case of reversion.[11]

Environmental factors such as drugs or infections can cause IgAD, but this form is reversible in more than half the cases (see Causes).

Although individuals with IgAD have largely been considered healthy, recent studies indicate a higher rate of symptoms. A 20-year follow-up study that compared 204 healthy blood donors with incidentally identified IgAD to 237 healthy subjects with normal IgA levels demonstrated that 80% of IgAD donors and 50% of control subjects had episodes of infections, drug allergy, or autoimmune or atopic disease. Severe respiratory tract infections occurred in 26% of IgAD subjects, in 24% of subjects with decreased IgA levels, and in 8% of control subjects; however, the incidence of life-threatening infections was not increased. IgAD is more common in adult patients with chronic lung disease than in healthy age-matched control subjects.[12]

Patients with IgAD are at some increased risk of developing severe reactions after receiving blood products.[13, 14, 15] IgG anti-IgA antibodies may cause severe transfusion reactions if patients with IgAD are given whole blood; therefore, IgA-poor blood or washed red cells are preferred for those patients. IgA-deficient patients with immunoglobulin E (IgE)–class anti-IgA antibodies are at risk for anaphylaxis if they receive blood or intravenous immunoglobulin, but this situation is extremely rare. Individuals with such an unusual profile should receive only low IgA intravenous immunoglobulin preparations. However, caution must be used when administering IGIV to patients with IgAD if their anti-IgA status is unknown.

A history devoid of previous blood product administration does not exclude the possibility of anti-IgA antibodies or adverse reactions. Fortunately, appropriate precautions can significantly reduce morbidity (see Treatment). Blood banks can use a simple ELISA screening approach to establish an IgAD blood donor pool.[16]


IgA is the second most common immunoglobulin in human serum (after IgG) and is the predominant immunoglobulin found in mucosal secretions. Most investigators conclude that more IgA is actually produced than any other immunoglobulin, since most of it is lost in secretions.

Structurally, IgA has 2 different forms. Most serum IgA is monomeric, while secretory IgA is a dimer that contains an extra protein chain referred to as the "secretory component;" it is this property that makes this unique immunoglobulin resistant to the proteolytic enzymes found in many human secretions. The IgA dimer and the J-chain that holds the 2 IgA monomers together are produced by B cells. The secretory component is added by the serous cells in the mucoserous glands that transport dimeric IgA and other polymeric immunoglobulins (ie, IgM) onto the mucous membranes; a fragment of the receptor/transport protein mediates this translocation. Deficiency of this "polymeric Ig receptor" has been reported, and knock-out mice have been developed in the laboratory. In this situation, the serum IgA level becomes elevated because the IgA cannot be transported out of the blood into the secretions.

Secretory IgA antibodies can neutralize viruses, bind toxins, agglutinate bacteria, prevent bacteria from binding to mucosal epithelial cells, and bind to various food antigens, thus preventing their entry into the general circulation. The activities of monomeric serum IgA are not fully understood. Dimeric serum IgA probably represents a kinetically defined pool that has not yet been transported.

IgAD is a primary immunodeficiency disease presumed to result from a failure of terminal differentiation in IgA-positive B cells. The development of B-lineage cells begins in the fetal liver. B-lineage cell development then transfers to the bone marrow, when it becomes the major hematopoietic organ. Pre–B cells become immature immunoglobulin M (IgM)–positive B cells and then migrate from the bone marrow to lymph node germinal centers. After leaving the bone marrow, the B cells mature and express immunoglobulin D (IgD) receptors, respond to antigens, and, with the help of T cells (CD4+), undergo proliferation and class switching and terminal differentiation into plasma cells.[12]

In germinal centers, antigen is presented by follicular dendritic cells with help from CD4+ T cells and stimulates B cells to proliferate and undergo somatic mutation and immunoglobulin class-switching. B cells that produce high-antigen affinity antibodies are selected to develop into plasma cells that produce different immunoglobulin isotypes (ie, IgM, IgG, IgA, or IgE) or become recirculating memory B lymphocytes. These processes are regulated by cell interaction molecules (eg, CD40 on B cells, CD40 ligand on activated T cells, ICOS, TACI-TACIR, etc), and cytokines (ie, interferon-gamma and interleukin [IL]–2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-13, IL-14, and IL-15) and their cell surface receptors.[12]

Most patients with IgAD have a normal number of B cells expressing surface IgA in their blood, but the amount of surface IgA on each B cell is markedly decreased. Based on animal studies, the failure of B cells to terminally differentiate into IgA-secreting plasma cells may be due to the lack of effects caused by co-stimulatory molecules or cytokines such as IL-4, IL-6, IL-7, or IL-10.

Molecular analyses of B-cell differentiation in a small number of patients with selective or partial IgAD suggest that decreased expression level of alpha germline transcripts before a class switch might be critical for the pathogenesis of some patients with SIgAD. A case report from Japan described using reverse transcription polymerase chain reaction (RT-PCR) to separately evaluate alpha1 and alpha2 mRNAs and described a second case of alpha1 gene deletion, which manifested as a partial IgAD.[17] Another possible explanation is allelic variation in the heavy chain 3" regulatory region. A group in Canada evaluated HS1.2 allelic frequencies in 88 SIgAD patients and 101 controls, demonstrating a 39% homozygosity of the allele *1 in patients and 15% homozygosity in controls.[18]

In patients with a partial IgA deficiency, B-cell differentiation might be disturbed after a class switch.[19] The TACI receptor and 2 ligands (BAFF and APRIL) likely play a role in the pathogenesis of defective humoral immunity. BAFF is B-cell activating factor, and APRIL is a proliferation-inducing ligand. TACI is a tumor necrosis receptor superfamily member that is involved in lymphocyte maturation and survival. In mice, deletion of the sequences coding for TACI or BAFF (B-lymphocytestimulator [BLyS]) interfere with B-cell class switching and result in IgA deficiency.

Missense mutations in one allele of TACI were found in 4 of 19 unrelated individuals with CVID and in 1 of 16 individuals with SIgAD. The B cells from individuals with the TACI mutations expressed TACI but did not produce IgG and IgA in response to a TACI ligand, a finding thought to reflect impaired isotype switching.[20, 21, 6, 22, 23]

IgAD has been noted to evolve into CVID and is often observed in pedigrees that contain individuals with CVID.[24] Evidence for a common pathogenesis of CVID and IgAD include shared susceptibility alleles of major histocompatibility complex class III genes (D locus),[25] a similar spectrum of IgG subclass deficiencies, a gradual decline of immunoglobulin levels in concordant siblings, and the development of CVID in some patients with IgAD.

Previous studies of multiple-case families of patients with IgAD showed a higher prevalence of CVID among close relatives than in the general population. In multiple-case families with dominant transmission of CVID and IgAD, CVID was usually present in parents, followed by IgAD in the descendants. That study indicated the presence of a predisposing locus in the proximal part of the major histocompatibility complex. The recurrence risk was found to depend on the sex of the parents transmitting the defect. Affected mothers were more likely to produce offspring with IgAD than affected fathers.[8, 26, 27, 7]

IgAD has been reported in patients with constitutional chromosome 18 abnormalities, and a case series of 83 cases of 18p- syndrome showed an increased frequency of IgAD; however, attempts to identify a specific locus on chromosome 18 have not been successful.[7]

The ability of many patients with SIgAD to avoid respiratory infections may relate to compensatory mechanisms at the respiratory mucosal surface and/or compensatory increases in IgG. Nasal lavage samples obtained from patients with SIgAD compared to normal control show 10-fold higher median IgM levels and 3-fold higher median IgG levels.[28] An elevated nasal lavage level of the inflammatory cytokine IL-8 but not eosinophilic cationic protein (ECP) or TNF-α indicates a level of subclinical inflammation in these patients.

Nasal biopsy specimens from patients with SIgAD analyzed by Brandtzaeg et al associated a lower incidence of respiratory tract infections and an elevated ratio of IgM-producing cells to IgD-producing cells in the mucosa.[29] Patients with recurrent acute rhinosinusitis, otitis media, and tonsillitis had a dominance of the IgD over the IgM isotype, leading the investigators to conclude that immunoregulatory events favoring a dominant local IgD response did not support mucosal defense. Rose's data showed a wide range of IgM levels among patients with IgAD patients (0.87-5.2 μg/mL) but did not provide correlative clinical information.[28]

Structural lung disease such as chronic obstructive pulmonary disease (COPD) was previously thought not to associate with the ability to generate antigen-specific IgA. Studies of acute exacerbations of chronic bronchitis show that new mucosal IgA to surface-exposed epitopes of the infecting Moraxella catarrhalis isolate developed in sputum supernatants after 42% of exacerbations,[30] and significant increases in mycoplasmal-specific IgA occurred in 85% of a group of 34 patients hospitalized for acute exacerbations of COPD. In a prospective study of 250 hospitalizations for acute exacerbations of COPD, the geometric mean serum titer for IgG and IgA against Chlamydia pneumoniae was higher, with 33% meeting criteria for chronic infection.[31] In another series from India, serum and sputum IgA levels were higher in subjects with COPD than in control subjects.[32]

Recent studies, however, suggest that the mucosal IgA response is impaired in COPD with deficient transport of IgA across the bronchial epithelium, possibly involving degradation of the Ig receptor involved in transepithelial routing.[33] Like IgA deficiency, COPD/chronic bronchitis is a heterogeneous disorder, and some cases of primary defects in mucosal function (eg, cystic fibrosis) may actually be associated with increased IgA in the secretions.

Observations that SIgAD is associated with an increased prevalence of atopy suggest a possible role for IgA in asthma pathogenesis. A protective role of IgA has been seen in murine models of asthma.[33] It seems likely that in the absence of IgA, mucosal antigen exposure is increased, which may lead to increased IgE against inhalants or food antigens.

A case control study evaluated bronchial hyperresponsiveness in children with SIgAD (n = 20), children with normal IgA levels but sensitized to aeroallergens (n = 70) and children with normal IgA levels and negative skin prick tests (non-atopic) (n = 102). The children with SIgAD had lower forced vital capacity (FVC) but similar forced expiratory volume in 1 second (FEV1) values. Bronchial hyperreactivity was present in 30-35% of the children in the first 2 groups but in only 6% of the control group. The bronchial hyperreactivity among the children with SIgAD correlated with dust mite allergy but not with general atopy.[34]

Patients with partial IgAD can have diseases in which IgA is central to the pathogenesis. For example, a screening project identified 3 cases of partial IgA deficiency in patients with dermatitis herpetiformis, with IgA endomysial and tissue transglutaminase antibodies present in 2 of the patients. The authors conclude that pathogenically directed IgA antibodies were sufficient for cutaneous IgA deposition despite low serum IgA levels.[35]



United States

At a minimum, an estimated 250,000 individuals have IgAD in the United States.[36] In African Americans, the prevalence of IgAD is 1 case per 6000 persons. IgA levels are estimated to be abnormally low in 1:500 subjects, with the incidence as high as 1:100 atopic individuals. Complete absence of IgA is less frequent.


Factors associated with the prevalence of IgAD include a family history of IgAD and the country of origin. Family studies using IgAD blood donors as probands show that first-degree relatives have a 7.5% prevalence rate of IgAD, which is 38-fold higher than that of unrelated donors.[37] The serological prevalence of IgAD varies 100-fold among populations. Prevalences, in decreasing order, are as follows:

Isolated IgAD is present in a minority of cases of transient hypogammaglobulinemia of infancy. Of a series of 40 patients presenting with recurrent responsive infections, otitis media, bronchitis or bronchial asthma, or recurrent gastroenteritis when aged 4-29 months, only 1 had isolated IgAD, 10 had reduced IgG and IgA levels, and 6 had diminished IgA and IgM levels.[39] The majority recovered immunoglobulin levels by age 3 years, but 3 had persistently low IgG and IgA levels.

A study performed by Weber-Mzell et al on 7293 healthy white volunteers demonstrated an IgAD prevalence of 0.21% (definition of IgAD was level < 0.07g/L).[40] The same study showed seasonal fluctuations of serum IgA (SIgA) concentration; levels of SIgA increased in winter.

The Latin American Group for Primary Immunodeficiency Diseases is using a registry approach to increase disorder recognition in their region. Among a total of 3321 patients registered, 53% had an antibody deficiency, of which IgAD was the more frequent phenotype.[41]


IgAD is more frequent in adult subjects with chronic lung disease than in a healthy, age-matched control subjects.[12]

The 20-year longitudinal study of healthy blood donors with incidental findings of IgAD used questionnaires and medical record reviews and found a 3-fold increase in rates of severe childhood respiratory conditions (9% vs 3%), a 4-fold increase in rates of severe adult respiratory conditions (16% vs 4%), a similar increase in recurrent mild respiratory tract infections, and a significant increase in rates of recurrent viral infections (16% vs 1%).

This study also noted a 4-fold increase in the rate of autoimmune conditions (23% in subjects with SIgAD vs 5% in control subjects); a 2.5-fold increase in the rate of abdominal symptoms caused by milk (16% vs 6%); and slight increases in the rates of atopic eczema (8% vs 5%), drug allergy (9% vs 5%), and food hypersensitivity (3% vs 1%). A slight decrease was observed in the rate of allergic rhinitis and/or eczema (11% vs 17%).

When IgAD is associated with one or more IgG subclass deficiencies or impaired polysaccharide responsiveness, some individuals with IgAD may develop recurrent sinopulmonary infections, especially in patients with concurrent IgG 2 and/or 4 subclass deficiency. This condition has been found to underlie some cases of familial deafness due to severe recurrent otitis.[42] GI tract infections and disorders in patients have been reported more frequently with absent secretory IgA, as has an increased incidence of cancer. Lack of secretory IgA has been hypothesized to compromise the defense against infection with Helicobacter pylori, which is thought to be a cause of stomach cancer.

The incidence of cancer among 562 Danish and Swedish subjects with CVID or IgA was compared with that of 2017 relatives for the period 1958-1996. Among 176 subjects with CVID, the incidence of cancer (all sites) was increased (standardized incidence ratio [SIR], 1.8; 95% confidence interval [CI], 1-2.9). Stomach cancer was increased (SIR, 10.3; 95% CI, 2.1-30.2), and malignant lymphoma was increased (SIR, 12.1; 95% CI, 3.3-31). Among 386 subjects with IgAD, the incidence of cancer (all sites) was not increased (SIR, 1); however, the incidence of stomach cancer was increased, albeit to an insignificant degree (SIR, 5.4; CI, 0.7-19.5).[43] The same study did not show an increase in lymphoid malignancies (non-Hodgkin lymphoma, Hodgkin disease) in IgAD subjects, even though some evidence in the literature indicates that the risk of developing a lymphoid malignancy is increased.[44]

A recent report described 63 Israeli children with SIgAD followed for 10 years, with malignancies diagnosed in 3 children (4.8%).[45]

Patients with IgAD who have a compensatory increase in IgM in their upper respiratory tract secretions and GI fluids tend to be less symptomatic. Note that patients with total IgAD are usually more symptomatic than patients partial IgAD.

Recurrent sinopulmonary infections are reported. IgAD usually manifests as recurrent otitis (in children), tonsillitis, sinusitis, and bronchitis with extracellular encapsulated bacteria (eg, Haemophilus influenzae, Streptococcus pneumoniae). Severe respiratory tract infections occur more often in adult subjects with IgAD than in normal control subjects, with a cumulative prevalence rate over 20 years of 16%. See the images below.

View Image

Chest radiograph of a 50-year-old man with immunoglobulin A deficiency and severe bilateral pneumonia. He also had congenital heart disease. Serum imm....

View Image

Lateral chest radiograph of a 50-year-old man with immunoglobulin A deficiency and severe bilateral pneumonia.

View Image

Portable chest radiograph of a 50-year-old man with acute respiratory distress syndrome as a complication of severe bilateral pneumonia. The patient d....

The substantial risk of developing lung damage, which is often reported in patients with CVID, is not a major threat to individuals who onlyhave SIgAD. In contrast, lung function is often significantly impaired among patients who have a combination of IgAD and a deficiency of one or more IgG subclasses. A few recently published cases reported the occurrence of hypersensitivity pneumonitis in patients with SIgAD and the authors suggest that SIgAD is a risk factor for a more severe course of the disease and increased susceptibility to develop extrinsic allergic alveolitis.[51, 52]

Autoimmune disease is reported in approximately 20% of patients with CVID and may be associated with IgAD.

The prevalence rate of IgG anti-IgA antibodies among white persons with IgAD is 30-40%. In patients with combined IgA-IgG subclass 2 deficiency, the rate is 50-60%. In contrast, the prevalence of IgE antibodies against IgA is extremely low.

IgA-deficient patients with anti-IgA antibodies may develop severe reactions when they are transfused with blood components that contain IgA. In the rare cases of true anaphylaxis, these antibodies are typically of the IgE class; however, anti-IgA antibodies of the IgG isotype can also cause anaphylactic-type reactions.[57] Although anaphylactic reactions occur in 1 in 20,000-47,000 transfusions, they constitute one of the frequent nonhemolytic causes of transfusion-related mortality.

A recent case described a patient with SIgAD who developed an anaphylactic reaction to a prothrombin complex concentrate; the authors stated that product information did not list IgAD as a contraindication.[58] A recent case report described the successful management of an SIgAD patient who required massive blood transfusion during emergency cesarean delivery.[59] New data quantify the risk of allergic reactions in recipients of blood components containing anti-IgA (ie, blood donated by SIgAD donors). A Canadian donor database was cross-referenced with transfusion reaction records; the incidence of allergic reactions was 1.15% in the anti-IgA group and 2.04% in the group that did not receive anti–IgA-containing blood.[60]

GI tract infections, including chronic or recurrent giardiasis and other disorders, are reported with increased frequency. Patients with SIgAD have a 10-fold increased risk of celiac disease. Milk intolerance is common in patients with primary IgAD. Reports indicate that patients with IgAD may have IgG antibodies against cow milk and ruminant serum proteins. Patients with high titers of antibodies to cow milk reportedly are more likely to have other autoantibodies.[61] A patient with SIgAD may still mainfest IgA antibody against select targets, such as transglutaminase and endomysium, as reported in one case of celiac disease in which IgG-specific antibodies were negative.[62]

Other conditions, such as ulcerative colitis, inflammatory bowel disease, Crohn disease, and pernicious anemia, have been described in IgA-deficient individuals. Friman et al showed that individuals with SIgAD have an increased risk of becoming a carrier of E coli strains that have increased proinflammatory properties, and hypothesize that this may contribute to the development of gastrointestinal disorders in SIgAD patients.[63] Mucosal infections include acute diarrhea caused by viruses, bacteria, or Giardia lamblia parasites. A higher occurrence of serum antibodies to milk antigens in patients with IgAD suggests that normal serum IgA responses protect the host from continuing exposure to environmental antigens.

An adult sIgAD patient who worked as scaffolder and was an avocational aquarist developed concomitant cutaneous Mycobacterium haemophilum and Mycobacterium kansasii infections, infections that are typically seen only in HIV-infected or posttransplantation patients.[64]

In a case report, a girl with ring chromosome 18 (46XX, r18) had SIgAD in addition to dysmorphic features, failure to thrive, global delay of development, hypothyroidism, atopic dermatitis, bilateral chronic otitis media and aortic regurgitation with patent foramen ovale.[65]

Quality of life (QOL) studies address the cumulative impact of living with a chronic disease such as SIgAD. Several standardized scales were administered to all patients with primary antibody deficiencies seen by a single Norwegian hospital. Low QOL scores were related to unemployment, infections in more than 4 organs, and more than 2 additional diseases. Persons with SIgAD had significantly higher QOL index scores than those with other antibody deficiencies.[66]


IgAD occurs in Arab persons at a rate of 1 case per 142 persons, in white persons at a rate of 1 case per 500-700 persons, in African American persons at a rate of 1 case per 6000 persons, and in Asian persons at a rate of 1 case per 14,840-18,500 persons.


A study of 7293 Austrian volunteers showed a greater frequency of SIgAD in men than in women (0.19% vs 0.014%) and a greater frequency of subnormal serum IgA levels (0.07-0.7 g/L) in men (2.66%) than in women (0.93%).[40]


This disease can be diagnosed in persons of any age.

Average serum IgA levels increase 0.2 ±0.06 g/L per decade of life.[40]


Previous studies based on analysis of blood donor banks have suggested that up to 90% of patients with selective immunoglobulin A deficiency (SIgAD) are asymptomatic. However, recent follow-up studies demonstrate that 80% of individuals with IgAD developed symptoms later in their life.[70] Symptomatic patients have a history significant for recurrent otitis media, sinusitis, bronchitis, pneumonia, GI tract infections, severe allergic reaction following infusions with immunoglobulins or blood transfusions, or, in children, failure to thrive.


Patients present with various signs of recurrent respiratory tract infections; including swelling, pain, or tenderness upon palpation over the maxillary and frontal sinuses; chronic otorrhea and/or scarred or perforated tympanic membranes and decreased auditory acuity or even deafness; chronic nasal discharge; fever; nonproductive or productive cough; and dyspnea. GI findings may include abdominal distention, focal tenderness to direct palpation (without rebound), cramps after eating, diffuse pain, and increased peristalsis.[72, 73]


The underlying causes of most cases of this heterogeneous disease remain unknown. Familial inheritance has been recognized in 25% of affected individuals, suggesting a strong genetic influence.

Laboratory Studies

See the list below:

Imaging Studies

See the list below:

Other Tests

See the list below:

Medical Care

The approach to treatment includes identification of comorbid conditions; preventive measures to reduce the risk of infection; and prompt, rigorous, and effective treatment of infections. Functional endoscopic sinus surgery can frequently help relieve chronic obstruction and promote drainage. Tympanostomy tubes may also be helpful in reducing the risk of decreased hearing and secondary defective speech development in children with chronic suppurative otitis related to antibody deficiency.

Surgical Care

Some patients with recurrent sinusitis require surgical interventions to promote drainage.


See the list below:


Dietary modifications may be necessary to manage chronic diarrhea and malabsorption or food allergy. A gluten-free diet and, possibly, other restricted diets are important for treatment in patients with celiac disease or who have IgG antibodies to animal proteins in milk or other foods.


A priori restrictions are not necessary, but patients with chronic lung disease may have decreased exercise tolerance.

Medication Summary

Immunoglobulin A deficiency (IgAD) has no specific treatment. Replacement therapy is not practical for IgAD because of the short half-life of IgA and the relative paucity of IgA in commercial immunoglobulin preparations.

Antibiotic therapy is the first line of treatment, specific for sinopulmonary or GI tract infections. Associated sinopulmonary infections are treated according to treatment protocols used for community-acquired respiratory tract infections in healthy persons, but prolonged treatment may be necessary.

Immunization with pneumococcal and other polysaccharide vaccines is important; however, not all patients are able to mount an immune response. Postvaccination IgG titers can be obtained to confirm the presence of an age-appropriate protective level of antipneumococcal IgG. Patients with common variable immunodeficiency (CVID) or more subtle specific antibody deficiencies may be unable to mount a response to polysaccharide antigens; therefore, pneumococcal vaccination in CVID patients is often ineffective.

Use of IGIV as replacement therapy is not indicated for selective IgAD per se. In selected circumstances in patients with concomitant SIgAD and selective IgG antibody deficiency who have recurrent or chronic high-grade sinopulmonary infections, a trial of IGIV may be given to see if a substantial clinical response occurs. Most patients with IgAD as part of CVID and/or with concomitant specific IgG antibody deficiency can safely receive intravenous (IV) or subcutaneous (SC) IgG replacement therapy.[36, 81]

Patients with known or possible anti-IgA antibodies are still at increased risk of anaphylaxis or severe IgG-mediated reactions.

Precautions must be used in the administration of IV immunoglobulin and other blood products in patients with IgAD because IV immunoglobulin preparations and other blood products contain at least small amounts of IgA.

Pneumococcal vaccine polyvalent (PPV23; Pneumovax 23; Pnu-Imune 23)

Clinical Context:  Contains capsular polysaccharides of 23 pneumococcal types, which comprise 98% of pneumococcal disease isolates. For use in children >2 y and adults at increased risk of pneumococcal disease and its complications because of other underlying health conditions. Also benefits adults ≥ 65 y.

Pneumococcal vaccine heptavalent (PCV7; Prevnar)

Clinical Context:  Pneumococcal conjugate vaccine approved for infants and toddlers. Contains 7 purified capsular polysaccharides of S pneumoniae serotypes, accounting for 71% of infection among children < 24 m, each coupled with a nontoxic variant of diphtheria toxin, CRM 197.

Licensed for use in infants and young children in Feb 2000. Recommended for children aged 2-23 mo and for children aged 24-59 mo who are at increased risk for pneumococcal disease (eg, with sickle cell disease, HIV infection, other immunocompromising or chronic medical conditions). Licensed for infants aged ≥ 6 wk.

Class Summary

Used to induce active immunity.


See the list below:


See the list below:


See the list below:

Patient Education

See the list below:


Marina Y Dolina, MD, Consulting Physician, Wellspan Lung, Sleep and Critical Care Consultants and Pulmonary Services, York Hospital, Wellspan Health System

Disclosure: Nothing to disclose.


Rebecca Bascom, MD, MPH, Professor of Medicine, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Pennsylvania State College of Medicine, Milton S Hershey Medical Center; Graduate Faculty Member, Pennsylvania State University College of Medicine and The Huck Institutes of the Life Sciences

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Michael R Simon, MD, MA, Clinical Professor Emeritus, Departments of Internal Medicine and Pediatrics, Wayne State University School of Medicine; Professor, Department of Internal Medicine, Oakland University William Beaumont University School of Medicine; Adjunct Staff, Division of Allergy and Immunology, Department of Internal Medicine, William Beaumont Hospital

Disclosure: Have a 5% or greater equity interest in: Secretory IgA, Inc. ; siRNAx, Inc.<br/>Received income in an amount equal to or greater than $250 from: siRNAx, Inc.

Chief Editor

Michael A Kaliner, MD, Clinical Professor of Medicine, George Washington University School of Medicine; Medical Director, Institute for Asthma and Allergy

Disclosure: Nothing to disclose.

Additional Contributors

Melvin Berger, MD, PhD, Adjunct Professor of Pediatrics and Pathology, Case Western Reserve University; Senior Medical Director, Clinical Research and Development, CSL Behring, LLC

Disclosure: Received salary from CSL Behring for employment; Received ownership interest from CSL Behring for employment; Received consulting fee from America''s Health insurance plans for subject matter expert for clinical immunization safety assessment network acvtivity of cdc.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Bettina C Hilman, MD, to the development and writing of this article.


  1. Bonilla FA, Bernstein IL, Khan DA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005 May. 94(5 Suppl 1):S1-63. [View Abstract]
  2. Daele J, Zicot AF. Humoral immunodeficiency in recurrent upper respiratory tract infections. Some basic, clinical and therapeutic features. Acta Otorhinolaryngol Belg. 2000. 54(3):373-90. [View Abstract]
  3. Wang N, Hammarström L. IgA deficiency: what is new?. Curr Opin Allergy Clin Immunol. 2012 Dec. 12(6):602-8. [View Abstract]
  4. Spickett GP, Misbah SA, Chapel HM. Primary antibody deficiency in adults. Lancet. 1991 Feb 2. 337(8736):281-4. [View Abstract]
  5. Longhurst HJ, O'Grady C, Evans G, De Lord C, Hughes A, Cavenagh J, et al. Anti-D immunoglobulin treatment for thrombocytopenia associated with primary antibody deficiency. J Clin Pathol. 2002 Jan. 55(1):64-6. [View Abstract]
  6. Hammarstrom L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol. 2000 May. 120(2):225-31. [View Abstract]
  7. Vorechovsky I, Webster AD, Plebani A, Hammarstrom L. Genetic linkage of IgA deficiency to the major histocompatibility complex: evidence for allele segregation distortion, parent-of-origin penetrance differences, and the role of anti-IgA antibodies in disease predisposition. Am J Hum Genet. 1999 Apr. 64(4):1096-109. [View Abstract]
  8. Vorechovsky I, Blennow E, Nordenskjold M, et al. A putative susceptibility locus on chromosome 18 is not a major contributor to human selective IgA deficiency: evidence from meiotic mapping of 83 multiple-case families. J Immunol. 1999 Aug 15. 163(4):2236-42. [View Abstract]
  9. Pan-Hammarstrom Q, Salzer U, Du L, et al. Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. Nat Genet. 2007 Apr. 39(4):429-30. [View Abstract]
  10. Koskinen S, Tolo H, Hirvonen M, Koistinen J. Long-term persistence of selective IgA deficiency in healthy adults. J Clin Immunol. 1994 Mar. 14(2):116-9. [View Abstract]
  11. Desar IM, Weemaes CM, van Deuren M, van der Meer JW. Reversible hypogammaglobulinaemia. Neth J Med. 2007 Nov. 65(10):381-5. [View Abstract]
  12. International Union of Immunological Societies. Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. Clin Exp Immunol. 1999 Oct. 118 Suppl 1:1-28. [View Abstract]
  13. Sazama K. Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion. 1990 Sep. 30(7):583-90. [View Abstract]
  14. Rogers RL, Javed TA, Ross RE, et al. Transfusion management of an IgA deficient patient with anti-IgA and incidental correction of IgA deficiency after allogeneic bone marrow transplantation. Am J Hematol. 1998 Apr. 57(4):326-30. [View Abstract]
  15. Sanz C, Freire C, Ordinas A, Pereira A. An enzyme-linked immunosorbent assay applicable to screen blood donors for IgA deficiency. Haematologica. 1999 Oct. 84(10):887-90. [View Abstract]
  16. Thibault L, Beausejour A, de Grandmont MJ, Long A, Goldman M, Chevrier MC. Establishment of an immunoglobulin A-deficient blood donor registry with a simple in-house screening enzyme-linked immunosorbent assay. Transfusion. 2006 Dec. 46(12):2115-21. [View Abstract]
  17. Kaneko H, Suzuki H, Kondo N. [IgA subclass and IgA deficiency]. Nihon Rinsho Meneki Gakkai Kaishi. 2009 Jun. 32(3):142-8. [View Abstract]
  18. Giambra V, Cianci R, Lolli S, et al. Allele *1 of HS1.2 enhancer associates with selective IgA deficiency and IgM concentration. J Immunol. 2009 Dec 15. 183(12):8280-5. [View Abstract]
  19. Asano T, Kaneko H, Terada T, et al. Molecular analysis of B-cell differentiation in selective or partial IgA deficiency. Clin Exp Immunol. 2004 May. 136(2):284-90.
  20. Castigli E, Geha RS. TACI, isotype switching, CVID and IgAD. Immunol Res. 2007. 38(1-3):102-11. [View Abstract]
  21. Castigli E, Wilson SA, Garibyan L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005 Aug. 37(8):829-34. [View Abstract]
  22. Hummelshoj L, Ryder LP, Nielsen LK, Nielsen CH, Poulsen LK. Class switch recombination in selective IgA-deficient subjects. Clin Exp Immunol. 2006 Jun. 144(3):458-66. [View Abstract]
  23. Jin R, Kaneko H, Suzuki H, Arai T, Teramoto T, Fukao T, et al. Age-related changes in BAFF and APRIL profiles and upregulation of BAFF and APRIL expression in patients with primary antibody deficiency. Int J Mol Med. 2008 Feb. 21(2):233-8. [View Abstract]
  24. Buckley RH. Immunodeficiency diseases. JAMA. 1992 Nov 25. 268(20):2797-806. [View Abstract]
  25. Cucca F, Zhu ZB, Khanna A, et al. Evaluation of IgA deficiency in Sardinians indicates a susceptibility gene is encoded within the HLA class III region. Clin Exp Immunol. 1998 Jan. 111(1):76-80. [View Abstract]
  26. Vorechovsky I, Cullen M, Carrington M, et al. Fine mapping of IGAD1 in IgA deficiency and common variable immunodeficiency: identification and characterization of haplotypes shared by affected members of 101 multiple-case families. J Immunol. 2000 Apr 15. 164(8):4408-16. [View Abstract]
  27. Vorechovsky I, Webster AD, Hammarstrom L. Mapping genes underlying complex disorders: progress on IgA deficiency and common variable immunodeficiency. Adv Exp Med Biol. 2001. 495:183-90. [View Abstract]
  28. Rose MA, Schubert R, Schmitt-Grohe S, Reichenbach J, Zielen S. Immunoglobulins and inflammatory cytokines in nasal secretions in humoral immunodeficiencies. Laryngoscope. 2006 Feb. 116(2):239-44. [View Abstract]
  29. Brandtzaeg P, Karlsson G, Hansson G, Peteruson B, Bjorkander J, Hanson LA. The clinical condition of IgA-deficient patients is related to the proportion of IgD- and IgM-producing cells in their nasal mucosa. Clinical & experimental Immunology. 1987/03. 67 Issue 3:626-636.
  30. Bakri F, Brauer AL, Sethi S, Murphy TF. Systemic and mucosal antibody response to Moraxella catarrhalis after exacerbations of chronic obstructive pulmonary disease. J Infect Dis. 2002 Mar 1. 185(5):632-40. [View Abstract]
  31. Lieberman D, Ben-Yaakov M, Lazarovich Z, et al. Chlamydia pneumoniae infection in acute exacerbations of chronic obstructive pulmonary disease: analysis of 250 hospitalizations. Eur J Clin Microbiol Infect Dis. 2001 Oct. 20(10):698-704. [View Abstract]
  32. Chauhan S, Gupta MK, Goyal A, Dasgupta DJ. Alterations in immunoglobulin & complement levels in chronic obstructive pulmonary disease. Indian J Med Res. 1990 Aug. 92:241-5. [View Abstract]
  33. Pilette C, Durham SR, Vaerman JP, Sibille Y. Mucosal immunity in asthma and chronic obstructive pulmonary disease: a role for immunoglobulin A?. Proc Am Thorac Soc. 2004. 1(2):125-35.
  34. Papadopoulou A, Mermiri D, Taousani S, Triga M, Nicolaidou P, Priftis KN. Bronchial hyper-responsiveness in selective IgA deficiency. Pediatr Allergy Immunol. 2005 Sep. 16(6):495-500. [View Abstract]
  35. Samolitis NJ, Hull CM, Leiferman KM, Zone JJ. Dermatitis herpetiformis and partial IgA deficiency. J Am Acad Dermatol. 2006 May. 54(5 Suppl):S206-9. [View Abstract]
  36. Gustafson R, Gardulf A, Granert C, et al. Prophylactic therapy for selective IgA deficiency. Lancet. 1997 Sep 20. 350(9081):865. [View Abstract]
  37. Oen K, Petty RE, Schroeder ML. Immunoglobulin A deficiency: genetic studies. Tissue Antigens. 1982 Mar. 19(3):174-82. [View Abstract]
  38. Chandran S, Khetan D, Chaudhary R, Misra R, Aggarwal A. Low prevalence of IgA deficiency in north Indian population. Indian J Med Res. 2006 May. 123(5):653-6. [View Abstract]
  39. Cipe FE, Dogu F, Güloglu D, Aytekin C, Polat M, Biyikli Z, et al. B-cell subsets in patients with transient hypogammaglobulinemia of infancy, partial IgA deficiency, and selective IgM deficiency. J Investig Allergol Clin Immunol. 2013. 23(2):94-100. [View Abstract]
  40. Weber-Mzell D, Kotanko P, Hauer AC, et al. Gender, age and seasonal effects on IgA deficiency: a study of 7293 Caucasians. Eur J Clin Invest. 2004 Mar. 34(3):224-8.
  41. Leiva LE, Zelazco M, Oleastro M, Carneiro-Sampaio M, Condino-Neto A, Costa-Carvalho BT, et al. Primary immunodeficiency diseases in Latin America: the second report of the LAGID registry. J Clin Immunol. 2007 Jan. 27(1):101-8. [View Abstract]
  42. Oxelius VA, Laurell AB, Lindquist B, et al. IgG subclasses in selective IgA deficiency: importance of IgG2-IgA deficiency. New Engl. J. Med. Jun 11, 1981. 304:1476-77. [View Abstract]
  43. Mellemkjaer L, Hammarstrom L, Andersen V, et al. Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study. Clin Exp Immunol. 2002 Dec. 130(3):495-500. [View Abstract]
  44. Cunningham-Rundles C, Zhou Z, Mankarious S, Courter S. Long-term use of IgA-depleted intravenous immunoglobulin in immunodeficient subjects with anti-IgA antibodies. J Clin Immunol. 1993 Jul. 13(4):272-8. [View Abstract]
  45. Shkalim V, Monselize Y, Segal N, Zan-Bar I, Hoffer V, Garty BZ. Selective IgA deficiency in children in Israel. J Clin Immunol. 2010 Sep. 30(5):761-5. [View Abstract]
  46. Fazekas T, Wiesbauer P, Schroth B et al. selective IgA deficiency in children with recurrent parotitis of childhood. Pediatr Infect Dis J. 2005 May. 24(5):461-2.
  47. Shkalim V, Monselise Y, Mosseri R, Finkelstein Y, Garty BZ. Recurrent parotitis in selective IgA deficiency. Pediatr Allergy Immunol. 2004 Jun. 15(3):281-3. [View Abstract]
  48. Tar I, Kiss C, Marodi L, Marton IJ. Oral and dental conditions of children with selective IgA deficiency. Pediatr Allergy Immunol. 2008 Feb. 19(1):33-6. [View Abstract]
  49. Nikfarjam J, Pourpak Z, Shahrabi M, Nikfarjam L, Kouhkan A, Moazeni M, et al. Oral manifestations in selective IgA deficiency. Int J Dent Hyg. 2004 Feb. 2(1):19-25. [View Abstract]
  50. Jorgensen GH, Arnlaugsson S, Theodors A, Ludviksson BR. Immunoglobulin A deficiency and oral health status: a case-control study. J Clin Periodontol. 2010 Jan. 37(1):1-8. [View Abstract]
  51. Yalcin E, Kiper N, Gocmen A, OzcelIk U, Dogru D, MisirligIl Z. Pigeon-breeder's disease in a child with selective IgA deficiency. Pediatr Int. 2003 Apr. 45(2):216-8. [View Abstract]
  52. Sennekamp J, Morr H, Behr J. Extrinsic allergic alveolitis with IgA deficiency. Eur J Med Res. 2004 Dec 22. 9(12):573-4. [View Abstract]
  53. Jorgensen GH, Ornolfsson AE, Johannesson A, et al. Association of immunoglobulin A deficiency and elevated thyrotropin-receptor autoantibodies in two Nordic countries. Hum Immunol. 2011 Feb. 72(2):166-72. [View Abstract]
  54. Barka N, Shen GQ, Shoenfeld Y, et al. Multireactive pattern of serum autoantibodies in asymptomatic individuals with immunoglobulin A deficiency. Clin Diagn Lab Immunol. 1995 Jul. 2(4):469-72. [View Abstract]
  55. Casquero A, Ramos A, Barat A, Mampaso F, Caramelo C, Egido J, et al. Recurrent acute postinfectious glomerulonephritis. Clin Nephrol. 2006 Jul. 66(1):51-3. [View Abstract]
  56. Betterle C, Lazzarotto F, Spadaccino AC, et al. Celiac disease in North Italian patients with autoimmune Addison's disease. Eur J Endocrinol. 2006 Feb. 154(2):275-9. [View Abstract]
  57. Bjorkander J, Hammarstrom L, Smith CI, et al. Immunoglobulin prophylaxis in patients with antibody deficiency syndromes and anti-IgA antibodies. J Clin Immunol. 1987 Jan. 7(1):8-15. [View Abstract]
  58. Chowdary P, Nair D, Davies N, Malde R, Gatt A. Anaphylactic reaction with prothrombin complex concentrate in a patient with IgA deficiency and anti-IgA antibodies. Blood Coagul Fibrinolysis. 2010 Dec. 21(8):764-5. [View Abstract]
  59. Steel C, Vaida S, Mets B. Case report: massive blood transfusion in a patient with immunoglobulin a deficiency undergoing cesarean delivery. Anesth Analg. 2010 Apr 1. 110(4):1088-90. [View Abstract]
  60. Robitaille N, Delage G, Long A, Thibault L, Robillard P. Allergic transfusion reactions from blood components donated by IgA-deficient donors with and without anti-IgA: a comparative retrospective study. Vox Sang. 2010 Aug 1. 99(2):136-41. [View Abstract]
  61. Cunningham-Rundles C, Brandeis WE, Pudifin DJ, et al. Autoimmunity in selective IgA deficiency: relationship to anti-bovine protein antibodies, circulating immune complexes and clinical disease. Clin Exp Immunol. 1981 Aug. 45(2):299-304. [View Abstract]
  62. Valletta E, Fornaro M, Pecori S, Zanoni G. Selective immunoglobulin A deficiency and celiac disease: let's give serology a chance. J Investig Allergol Clin Immunol. 2011. 21(3):242-4. [View Abstract]
  63. Friman V, Nowrouzian F, Adlerberth I, Wold AE. Increased frequency of intestinal Escherichia coli carrying genes for S fimbriae and haemolysin in IgA-deficient individuals. Microb Pathog. 2002 Jan. 32(1):35-42. [View Abstract]
  64. Bekou V, Büchau A, Flaig MJ, Ruzicka T, Hogardt M. Cutaneous infection by Mycobacterium haemophilum and kansasii in an IgA-deficient man. BMC Dermatol. 2011 Jan 26. 11:3. [View Abstract]
  65. Sripanidkulchai R, Suphakunpinyo C, Jetsrisuparb C, Luengwattanawanich S. Thai girl with ring chromosome 18 (46XX, r18). J Med Assoc Thai. 2006 Jun. 89(6):878-81. [View Abstract]
  66. Sigstad HM, Stray-Pedersen A, Froland SS. Coping, quality of life, and hope in adults with primary antibody deficiencies. Health Qual Life Outcomes. 2005 May 4. 3:31. [View Abstract]
  67. Gomez-Carrasco JA, Barrera-Gomez MJ, Garcia-Mourino V, et al. Selective and partial IgA deficiency in an adolescent male with bronchiectasis. Allergol Immunopathol (Madr). 1994 Nov-Dec. 22(6):261-3. [View Abstract]
  68. Lantz A, Armstrong J, Truemper E, et al. Immunoglobulin deficiency in children with a sudden overwhelming infection. Ann Allergy Asthma Immunol. 2001 Jan. 86(1):55-8. [View Abstract]
  69. Chen SM, Sheu JN, Chen JP, Yang MH. Community-acquired Pseudomonas aeruginosa pneumonia complicated with loculated empyema in an infant with selective IgA deficiency. Acta Paediatr Taiwan. 2002 May-Jun. 43(3):157-61. [View Abstract]
  70. Koskinen S. Long-term follow-up of health in blood donors with primary selective IgA deficiency. J Clin Immunol. 1996 May. 16(3):165-70. [View Abstract]
  71. Anani W, Triulzi D, Yazer MH, Qu L. Relative IgA-deficient recipients have an increased risk of severe allergic transfusion reactions. Vox Sang. 2014 Sep 15. [View Abstract]
  72. Jorgensen GH, Gardulf A, Sigurdsson MI, Sigurdardottir ST, Thorsteinsdottir I, Gudmundsson S, et al. Clinical symptoms in adults with selective IgA deficiency: a case-control study. J Clin Immunol. 2013 May. 33(4):742-7. [View Abstract]
  73. Tachdjian R. Complex regional pain syndrome treated with intravenous immunoglobulin in a patient with common variable immune deficiency. Pain Ther. 2013 Dec. 2(2):129-34. [View Abstract]
  74. de Laat PC, Weemaes CM, Bakkeren JA, et al. Familial selective IgA deficiency with circulating anti-IgA antibodies: a distinct group of patients?. Clin Immunol Immunopathol. 1991 Jan. 58(1):92-101. [View Abstract]
  75. Kirkeleit J, Ulvestad E, Riise T, Bratveit M, Moen BE. Acute suppression of serum IgM and IgA in tank workers exposed to benzene. Scand J Immunol. 2006 Dec. 64(6):690-8. [View Abstract]
  76. Booth JR, Munks R, Sokol RJ. Isolation of IgA1 from human serum by affinity chromatography using an immobilized extract of the albumin gland of Helix pomatia. Transfus Med. 1995 Jun. 5(2):117-21. [View Abstract]
  77. Oltean S, Epure A, Lindström K, Pardi C. Detection of anti-IgA antibodies using the particle gel immunoassay: a rapid test for increased patient safety. Blood Transfus. 2014 Jul. 12(3):334-9. [View Abstract]
  78. Rusconi F, Panisi C, Dellepiane RM et al. Pulmonary and sinus disease in primary humoral immunodeficiencies with chronic productive cough. Arch Dis Child. 2003 Dec. 88(12):1101-5. [View Abstract]
  79. Hermans PE, Diaz-Buxo JA, Stobo JD. Idiopathic late-onset immunoglobulin deficiency. Clinical observations in 50 patients. Am J Med. 1976 Aug. 61(2):221-37. [View Abstract]
  80. Kohler P. Pulmonary manifestations and management of antibody deficiency in adults. Chest. 1984 Sep. 86(3 Suppl):24S-28S. [View Abstract]
  81. Sundin U, Nava S, Hammarstrom L. Induction of unresponsiveness against IgA in IgA-deficient patients on subcutaneous immunoglobulin infusion therapy. Clin Exp Immunol. 1998 May. 112(2):341-6. [View Abstract]
  82. Vassallo RR. Review: IgA anaphylactic transfusion reactions. Part I. Laboratory diagnosis, incidence, and supply of IgA-deficient products. Immunohematol. 2004. 20:226-33.
  83. Sandler SG, Mallory D, Malamut D, Eckrich R. IgA anaphylactic transfusion reactions. Transfus Med Rev. 1995 Jan. 9(1):1-8. [View Abstract]
  84. Knight AK, Bingemann T, Cole L, Cunningham-Rundles C. Frequent false positive beta human chorionic gonadotropin tests in immunoglobulin A deficiency. Clin Exp Immunol. 2005 Aug. 141(2):333-7.
  85. Winters JL, Moore SB, Sandness C, Miller DV. Transfusion of apheresis PLTs from IgA-deficient donors with anti-IgA is not associated with an increase in transfusion reactions. Transfusion. 2004 Mar. 44(3):382-5.
  86. Dahlbom I, Olsson M, Forooz NK, Sjoholm AG, Truedsson L, Hansson T. Immunoglobulin G (IgG) anti-tissue transglutaminase antibodies used as markers for IgA-deficient celiac disease patients. Clin Diagn Lab Immunol. 2005 Feb. 12(2):254-8. [View Abstract]
  87. Lenhardt A, Plebani A, Marchetti F, et al. Role of human-tissue transglutaminase IgG and anti-gliadin IgG antibodies in the diagnosis of coeliac disease in patients with selective immunoglobulin A deficiency. Dig Liver Dis. 2004 Nov. 36(11):730-4. [View Abstract]
  88. Villalta D, Alessio MG, Tampoia M, et al. Diagnostic accuracy of IgA anti-tissue transglutaminase antibody assays in celiac disease patients with selective IgA deficiency. Ann N Y Acad Sci. 2007 Aug. 1109:212-20. [View Abstract]
  89. Wang N, Truedsson L, Elvin K, Andersson BA, Rönnelid J, Mincheva-Nilsson L, et al. Serological assessment for celiac disease in IgA deficient adults. PLoS One. 2014. 9(4):e93180. [View Abstract]
  90. Aittoniemi J, Koskinen S, Laippala P, et al. The significance of IgG subclasses and mannan-binding lectin (MBL) for susceptibility to infection in apparently healthy adults with IgA deficiency. Clin Exp Immunol. 1999 Jun. 116(3):505-8. [View Abstract]
  91. Alaswad B, Brosnan P. The association of celiac disease, diabetes mellitus type 1, hypothyroidism, chronic liver disease, and selective IgA deficiency. Clin Pediatr (Phila). 2000 Apr. 39(4):229-31. [View Abstract]
  92. Arulanandam BP, Raeder RH, Nedrud JG, et al. IgA immunodeficiency leads to inadequate Th cell priming and increased susceptibility to influenza virus infection. J Immunol. 2001 Jan 1. 166(1):226-31. [View Abstract]
  93. Badcock LJ, Clarke S, Jones PW, et al. Abnormal IgA levels in patients with rheumatoid arthritis. Ann Rheum Dis. 2003 Jan. 62(1):83-4. [View Abstract]
  94. Ballow M. Primary immunodeficiency disorders: antibody deficiency. J Allergy Clin Immunol. 2002 Apr. 109(4):581-91. [View Abstract]
  95. Braconier JH, Nilsson B, Oxelius VA, Karup-Pedersen F. Recurrent pneumococcal infections in a patient with lack of specific IgG and IgM pneumococcal antibodies and deficiency of serum IgA, IgG2 and IgG4. Scand J Infect Dis. 1984. 16(4):407-10. [View Abstract]
  96. Buckley RH. Advances in the diagnosis and treatment of primary immunodeficiency diseases. Arch Intern Med. 1986 Feb. 146(2):377-84. [View Abstract]
  97. Buckley RH. Primary Immunodeficiency Diseases. Middleton E Jr, Reed CE, Ellis EF, Adkinson NF Jr, Yunginger JW, Busse WW, eds. Allergy: Principles and Practice. 713-34.
  98. Buckley RH. Primary immunodeficiency diseases: dissectors of the immune system. Immunol Rev. 2002 Jul. 185:206-19. [View Abstract]
  99. Buckley RH, Schiff RI. The use of intravenous immune globulin in immunodeficiency diseases. N Engl J Med. 1991 Jul 11. 325(2):110-7. [View Abstract]
  100. Burks AW, Sampson HA, Buckley RH. Anaphylactic reactions after gamma globulin administration in patients with hypogammaglobulinemia. Detection of IgE antibodies to IgA. N Engl J Med. 1986 Feb 27. 314(9):560-4.
  101. Burrows PD, Cooper MD. IgA deficiency. Adv Immunol. 1997. 65:245-76. [View Abstract]
  102. Cardinale F, Friman V, Carlsson B, et al. Aberrations in titre and avidity of serum IgM and IgG antibodies to microbial and food antigens in IgA deficiency. Scand J Immunol. 1992 Aug. 36(2):279-83. [View Abstract]
  103. Carvalho Neves Forte W, Ferreira De Carvalho Junior F, Damaceno N, et al. Evolution of IgA deficiency to IgG subclass deficiency and common variable immunodeficiency. Allergol Immunopathol (Madr). 2000 Jan-Feb. 28(1):18-20. [View Abstract]
  104. Cataldo F, Marino V, Bottaro G, et al. Celiac disease and selective immunoglobulin A deficiency. J Pediatr. 1997 Aug. 131(2):306-8. [View Abstract]
  105. Cunningham-Rundles C. Clinical and immunologic analyses of 103 patients with common variable immunodeficiency. J Clin Immunol. 1989 Jan. 9(1):22-33. [View Abstract]
  106. Cunningham-Rundles C. Physiology of IgA and IgA deficiency. J Clin Immunol. 2001 Sep. 21(5):303-9. [View Abstract]
  107. Davies K, Stiehm ER, Woo P, Murray KJ. Juvenile idiopathic polyarticular arthritis and IgA deficiency in the 22q11 deletion syndrome. J Rheumatol. 2001 Oct. 28(10):2326-34. [View Abstract]
  108. Eckrich RJ, Mallory DM, Sandler SG. Laboratory tests to exclude IgA deficiency in the investigation of suspected anti-IgA transfusion reactions. Transfusion. 1993 Jun. 33(6):488-92. [View Abstract]
  109. French MA, Harrison G. An investigation into the effect of the IgG antibody system on the susceptibility of IgA-deficient patients to respiratory tract infections. Clin Exp Immunol. 1986 Dec. 66(3):640-7. [View Abstract]
  110. Friman V, Hanson LA, Bridon JM, et al. IL-10-driven immunoglobulin production by B lymphocytes from IgA- deficient individuals correlates to infection proneness. Clin Exp Immunol. 1996 Jun. 104(3):432-8. [View Abstract]
  111. Gutierrez MG, Kirkpatrick CH. Progressive immunodeficiency in a patient with IgA deficiency. Ann Allergy Asthma Immunol. 1997 Oct. 79(4):297-301. [View Abstract]
  112. Hahn DL. Chlamydia pneumoniae, asthma, and COPD: what is the evidence?. Ann Allergy Asthma Immunol. 1999 Oct. 83(4):271-88, 291; quiz 291-2. [View Abstract]
  113. Hanson LA, Bjorkander J, Carlsson B, et al. The heterogeneity of IgA deficiency. J Clin Immunol. 1988 May. 8(3):159-62. [View Abstract]
  114. Hanson LA, Soderstrom R, Nilssen DE, et al. IgG subclass deficiency with or without IgA deficiency. Clin Immunol Immunopathol. 1991 Nov. 61(2 Pt 2):S70-7. [View Abstract]
  115. Iizuka M, Itou H, Sato M, Yukawa M, Shirasaka T, Chiba M, et al. Crohn's disease associated with selective immunoglobulin a deficiency. J Gastroenterol Hepatol. 2001 Aug. 16(8):951-2. [View Abstract]
  116. Jones AL, Webb DJ. Selective IgA deficiency, hypothyroidism and congenital lymphoedema. Scott Med J. 1996 Feb. 41(1):22-3. [View Abstract]
  117. Kilic SS, Tezcan I, Sanal O, et al. Transient hypogammaglobulinemia of infancy: clinical and immunologic features of 40 new cases. Pediatr Int. 2000 Dec. 42(6):647-50. [View Abstract]
  118. Kinlen LJ, Webster AD, Bird AG, et al. Prospective study of cancer in patients with hypogammaglobulinaemia. Lancet. 1985 Feb 2. 1(8423):263-6. [View Abstract]
  119. Klemola T, Savilahti E, Arato A, et al. Immunohistochemical findings in jejunal specimens from patients with IgA deficiency. Gut. 1995 Oct. 37(4):519-23. [View Abstract]
  120. Koskinen S, Tolo H, Hirvonen M, Koistinen J. Long-term follow-up of anti-IgA antibodies in healthy IgA-deficient adults. J Clin Immunol. 1995 Jul. 15(4):194-8. [View Abstract]
  121. Kowalczyk D, Baran J, Webster AD, Zembala M. Intracellular cytokine production by Th1/Th2 lymphocytes and monocytes of children with symptomatic transient hypogammaglobulinaemia of infancy (THI) and selective IgA deficiency (SIgAD). Clin Exp Immunol. 2002 Mar. 127(3):507-12. [View Abstract]
  122. Kowalczyk D, Mytar B, Zembala M. Cytokine production in transient hypogammaglobulinemia and isolated IgA deficiency. J Allergy Clin Immunol. 1997 Oct. 100(4):556-62. [View Abstract]
  123. Kruszewska M, Kowalczyk D, Stopyrowa J, et al. Clinical manifestation of IgA deficiency. Rocz Akad Med Bialymst. 1995. 40(3):630-3. [View Abstract]
  124. Lilic D, Sewell WA. IgA deficiency: what we should-or should not-be doing. J Clin Pathol. 2001 May. 54(5):337-8. [View Abstract]
  125. Litzman J, Burianova M, Thon V, Lokaj J. Progression of selective IgA deficiency to common variable immunodeficiency in a 16 year old boy. Allergol Immunopathol (Madr). 1996 Jul-Aug. 24(4):174-6. [View Abstract]
  126. Marconi M, Plebani A, Avanzini MA, et al. IL-10 and IL-4 co-operate to normalize in vitro IgA production in IgA- deficient (IgAD) patients. Clin Exp Immunol. 1998 Jun. 112(3):528-32. [View Abstract]
  127. Matthews VB, Witt CS, French MA, et al. Central MHC genes affect IgA levels in the human: reciprocal effects in IgA deficiency and IgA nephropathy. Hum Immunol. 2002 May. 63(5):424-33. [View Abstract]
  128. Olerup O, Smith CI, Bjorkander J, Hammarstrom L. Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA-DQB1 gene, in IgA deficiency and common variable immunodeficiency. Proc Natl Acad Sci U S A. 1992 Nov 15. 89(22):10653-7. [View Abstract]
  129. Ott MM, Ott G, Klinker H, Trunk MJ, Katzenberger T, Muller-Hermelink HK. Abdominal T-cell non-Hodgkin's lymphoma of the gamma/delta type in a patient with selective immunoglobulin A deficiency. Am J Surg Pathol. 1998 Apr. 22(4):500-6. [View Abstract]
  130. Oxelius VA, Carlsson AM, Hammarstrom L, et al. Linkage of IgA deficiency to Gm allotypes; the influence of Gm allotypes on IgA-IgG subclass deficiency. Clin Exp Immunol. 1995 Feb. 99(2):211-5. [View Abstract]
  131. Paul AC, Justus A, Balraj A, et al. Malignant otitis externa in an infant with selective IgA deficiency: a case report. Int J Pediatr Otorhinolaryngol. 2001 Aug 20. 60(2):141-5. [View Abstract]
  132. Prince HE, Norman GL, Binder WL. Immunoglobulin A (IgA) deficiency and alternative celiac disease- associated antibodies in sera submitted to a reference laboratory for endomysial IgA testing. Clin Diagn Lab Immunol. 2000 Mar. 7(2):192-6. [View Abstract]
  133. Reil A, Bein G, Machulla HK, et al. High-resolution DNA typing in immunoglobulin A deficiency confirms a positive association with DRB1*0301, DQB1*02 haplotypes. Tissue Antigens. 1997 Nov. 50(5):501-6. [View Abstract]
  134. Sanal O, Ersoy F, Metin A, Tezcan I, Berkel AI, Yel L. Selective IgA deficiency with unusual features: development of common variable immunodeficiency, Sjogren's syndrome, autoimmune hemolytic anemia and immune thrombocytopenic purpura. Acta Paediatr Jpn. 1995 Aug. 37(4):526-9. [View Abstract]
  135. Schaffer FM, Palermos J, Zhu ZB, et al. Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes. Proc Natl Acad Sci U S A. 1989 Oct. 86(20):8015-9. [View Abstract]
  136. Schroeder HW Jr, Schroeder HW 3rd, Sheikh SM. The complex genetics of common variable immunodeficiency. J Investig Med. 2004 Mar. 52(2):90-103. [View Abstract]
  137. Seager J, Jamison DL, Wilson J, et al. IgA deficiency, epilepsy, and phenytoin treatment. Lancet. 1975 Oct 4. 2(7936):632-5. [View Abstract]
  138. Sorensen RU, Hidalgo H, Moore C, Leiva LE. Post-immunization pneumococcal antibody titers and IgG subclasses. Pediatr Pulmonol. 1996 Sep. 22(3):167-73. [View Abstract]
  139. Steuer A, McCrea DJ, Colaco CB. Primary Sjogren's syndrome, ulcerative colitis and selective IgA deficiency. Postgrad Med J. 1996 Aug. 72(850):499-500. [View Abstract]
  140. Tangsinmankong N, Bahna SL, Good RA. The immunologic workup of the child suspected of immunodeficiency. Ann Allergy Asthma Immunol. 2001 Nov. 87(5):362-9; quiz 370, 423. [View Abstract]
  141. van de Kerkhof PC, Steijlen PM. IgA deficiency and psoriasis: relevance of IgA in the pathogenesis of psoriasis. Dermatology. 1995. 191(1):46-8. [View Abstract]
  142. Zenone T, Souquet PJ, Cunningham-Rundles C, Bernard JP. Hodgkin's disease associated with IgA and IgG subclass deficiency. J Intern Med. 1996 Aug. 240(2):99-102. [View Abstract]

Chest radiograph of a 50-year-old man with immunoglobulin A deficiency and severe bilateral pneumonia. He also had congenital heart disease. Serum immunoglobulin G and immunoglobulin M levels were normal.

Lateral chest radiograph of a 50-year-old man with immunoglobulin A deficiency and severe bilateral pneumonia.

Portable chest radiograph of a 50-year-old man with acute respiratory distress syndrome as a complication of severe bilateral pneumonia. The patient died from respiratory failure 2 days after this x-ray film was taken.

Chest radiograph of a 50-year-old man with immunoglobulin A deficiency and severe bilateral pneumonia. He also had congenital heart disease. Serum immunoglobulin G and immunoglobulin M levels were normal.

Lateral chest radiograph of a 50-year-old man with immunoglobulin A deficiency and severe bilateral pneumonia.

Portable chest radiograph of a 50-year-old man with acute respiratory distress syndrome as a complication of severe bilateral pneumonia. The patient died from respiratory failure 2 days after this x-ray film was taken.