Selective IgA Deficiency

Overview

Selective IgA deficiency is the most common primary immunodeficiency, defined by very low or absent serum IgA levels with normal levels of other immunoglobulins (IgG, IgM). Many patients are asymptomatic, but some develop recurrent mucosal infections, allergic disease, or autoimmune disorders. Prevalence is estimated at 1:300 to 1:700 in Caucasian populations. Diagnosis is often incidental on routine blood tests, though symptomatic cases usually present in childhood or early adulthood.

Definition

IgA: Immunoglobulin found in mucosal secretions (respiratory tract, gut, saliva, breast milk) – provides frontline defence.
Primary immunodeficiency: Genetic/idiopathic defect of the immune system.
Anti-IgA antibodies: Antibodies directed against IgA, can cause anaphylaxis during blood transfusion.
Asymptomatic carrier: Patient with immunological abnormality but no clinical manifestations.

Anatomy & Physiology

IgA physiology: Produced by plasma cells in mucosa-associated lymphoid tissue (MALT).
Secretory IgA (sIgA): Dimeric form secreted across mucosal epithelia; protects against pathogens by neutralisation and blocking adhesion.
IgA also regulates microbiota balance and mucosal tolerance.
In SIgAD → absent/low IgA → impaired mucosal immunity → recurrent respiratory/GI infections and increased autoimmunity risk.

IgA is the first line of defence at mucosal surfaces.

Aetiology and Risk Factors

Aetiology

Unknown in most cases.
Possible genetic associations with HLA-B8, DR3, DQ2.
Can be part of a spectrum with CVID (some patients progress from SIgAD to CVID).

Risk Factors

Family history of primary immunodeficiency.
Higher prevalence in Caucasians.
Association with autoimmune disease (celiac, SLE, RA).

Pathophysiology

Defect in B-cell differentiation into IgA-secreting plasma cells.
Absent or markedly reduced IgA in serum and secretions.
Mucosal surfaces unprotected → recurrent respiratory/GI infections.
Dysregulated mucosal immunity → predisposition to allergy & autoimmunity.
Some patients develop anti-IgA antibodies → risk of transfusion anaphylaxis.

SIgAD is a failure of IgA production, not general B-cell absence.

Clinical Manifestations

Asymptomatic: ~50–70% of patients.
Recurrent mucosal infections: Sinopulmonary infections (pneumonia, sinusitis, otitis media), chronic diarrhoea, Giardia infections.
Allergic disorders: Asthma, allergic rhinitis, atopic disease.
Autoimmune disease: Celiac disease, SLE, RA, autoimmune thyroiditis.
Transfusion reactions: Anaphylaxis due to anti-IgA antibodies when given blood products with IgA.

Asymptomatic + transfusion anaphylaxis is a classic exam clue.

SIgAD Triad: Recurrent mucosal infections, allergic disease andutoimmunity (celiac, SLE, RA).

Diagnosis

Diagnostic criteria:
- Serum IgA <7 mg/dL (or undetectable).
- Normal IgG and IgM.
- Age >4 years (younger children may have physiologic low IgA).
- Exclusion of secondary causes (e.g., medications, protein loss).
Other tests: Normal vaccine responses; normal T-cell function.
Genetics: Not routinely required but can support diagnosis.

Differential Diagnosis

Condition	Key Differentiator
CVID	Low IgG ± IgM, poor vaccine response
Secondary hypogammaglobulinaemia	Drug-induced (phenytoin, sulfasalazine), nephrotic syndrome
Transient hypogammaglobulinaemia of infancy	Resolves with age

Treatment

No curative therapy; most patients require only observation.
Treat infections promptly with antibiotics.
Prophylactic antibiotics in recurrent/severe cases.
Avoid blood products containing IgA (or use washed RBCs/IgA-deficient plasma) if anti-IgA antibodies are present.
Manage comorbid allergic or autoimmune disease as standard.
IVIG replacement not useful unless associated IgG subclass deficiency.

Supportive care only – no role for routine immunoglobulin therapy in pure SIgAD.

Complications & Prognosis

Autoimmune disease (up to 30%).
Allergic disorders.
Anaphylaxis with transfusions.
Progression to CVID in some patients (~10–20%).
Prognosis generally excellent if asymptomatic.

SIgAD often found incidentally, but autoimmune disease and transfusion reactions are the high-yield risks.

SIgAD vs CVID

Feature	SIgAD	CVID
IgA	↓/absent	↓ (± IgG/IgM)
IgG	Normal	↓
Vaccine response	Normal	Impaired
Age of onset	Often childhood/adolescence	Later (childhood–adulthood)
Autoimmunity	Common	Common
Progression	Can progress to CVID	Established immunodeficiency

References

Yel L. Selective IgA deficiency. J Clin Immunol. 2010;30(1):10–6.
Ludvigsson JF, Neovius M, Hammarström L. Association between IgA deficiency & other autoimmune conditions: a population-based matched cohort study. J Clin Immunol. 2014;34(4):444–51.
Wang N, Hammarström L. IgA deficiency: what is new? Curr Opin Allergy Clin Immunol. 2012;12(6):602–8.
Picard C, Al-Herz W, Bousfiha A, et al. Primary Immunodeficiency Diseases: IUIS Classification Update. J Clin Immunol. 2015;35(8):696–726.
Latiff AH, Kerr MA. The clinical significance of immunoglobulin A deficiency. Ann Clin Biochem. 2007;44(2):131–9.