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Internal Medicine

Selective IgA deficiency (SIgAD)

Introduction

Selective immunoglobulin A (IgA) deficiency (SIgAD) is a genetic immunodeficiency, defined as undetectable serum IgA level in the presence of normal serum levels of IgG and IgM, in persons older than 4 years.

  • M/C primary antibody deficiency
  • Type of hypogammaglobulinemia

Epidemiology

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Frequency of IgA deficiency in normal population across the world. | Yazdani, R., Azizi, G., Abolhassani, H., & Aghamohammadi, A. (2017). Selective IgA Deficiency: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management. Scandinavian Journal of Immunology, 85(1), 3–12. https://doi.org/10.1111/sji.12499

Aetiology

Drug-induction:

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Pattern of drug-induced immunoglobulin deficiencies | Hammarström, L., Vorechovsky, I., & Webster, D. (2000). Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clinical and experimental immunology, 120(2), 225–231. doi:10.1046/j.1365-2249.2000.01131.x

Infections:

  • Cytomegalovirus (CMV)
  • Rubella
  • Toxoplasmosis
  • Epstein Barr virus (EBV)

Pathophysiology

Maturation defect in B cells to produce IgA:

B cells express IgA of immature phenotype with the coexpression of IgM and IgD (cannot fully develop into IgA-secreting plasma cells)

  • ↓ Serum and secretory IgA.
  • ↓ IgG subtypes: IgG2 and IgG4

Clinical features

Asymtptomatic (85-90% cases):

Most such persons remain healthy throughout their lives and are never diagnosed

Symptomatic cases:

Recurrent sinopulmonary infections, gastrointestinal infections and disorders, allergies, autoimmune conditions, and malignancies

Recurrent sinopulmonary infections (M/C, 40-90%):

  • Extracellular encapsulated bacteria: Haemophilus influenzae, Streptococcus pneumoniae)

Allergic diseases (25–50%):

  • Allergic conjunctivitis, rhinitis, urticaria, eczema, food allergy and asthma

Autoimmune conditions (5-30%):

  • Idiopathic thrombocytopenic purpura (ITP)
  • Graves’ disease
  • Autoimmune haemolytic anaemia
  • Type 1 diabetes mellitus
  • Rheumatoid arthritis (RA)
  • Thyroiditis
  • Systemic lupus erythematosus (SLE)
  • Coeliac disease

Gastrointestinal disorders:

  • Coeliac disease (M/C, 2-3%)
  • Giardiasis: Giardia lamblia
  • Nodular lymphoid hyperplasia (NLH)
  • Inflammatory bowel disease (IBD): Ulcerative colitis, Crohn’s disease
  • Pernicious anaemia
  • Gastric and colonic adenocarcinoma

Malignancies:

  • Common: Carcinoma stomach (M/C adenocarcinoma), lymphoma (M/C B cell origin)
  • Others: Colon cancer, ovarian cancer, lymphosarcoma, melanoma and thymoma

Complications

  • Panhypogammaglobulinemia

Diagnosis

European Society for Immunodeficiencies (ESID) criteria:

  • Serum IgA levels < 0.07 g/l + normal levels of IgG and IgM
  • Enhanced susceptibility to infections, especially respiratory
  • Diagnosis at > 4 years age
  • Concomitant autoimmune diseases and/or family member with the disease
  • Excluded secondary causes of hypogammaglobulinemia
  • Normal antibody (IgG) response to all vaccinations
  • Exclusion of T-cell defect

Management

Supportive care

  • Treatment of infections & co-morbid conditions

 

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