IgA

STRUCTURE & PRODUCTION - Serum IgA is mainly a monomer; secretory IgA is a dimer joined by a J chain and carries a secretory component. - Produced by plasma cells in mucosa-associated lymphoid tissue (e.g., Peyer patches). Class switching to IgA is driven by TGF-beta (plus IL-5, IL-21, and retinoic acid signals) acting on B cells. - Transport: dimeric IgA is secreted by plasma cells in the lamina propria. It binds the polymeric Ig receptor on the basolateral epithelial surface and is transcytosed to the lumen. The receptor is cleaved, and part of it stays attached as the secretory component. This component protects IgA from proteolytic degradation.

FUNCTION - Neutralizes toxins and microbes and blocks their adherence to the epithelium (immune exclusion). - Is the predominant antibody in breast milk (colostrum), which gives passive immunity to the neonate's gut. - Does not fix complement via the classical pathway, but can activate the alternative pathway. It is a weak opsonin. - Shapes the gut microbiome. - Most abundant antibody isotype produced overall, but IgG is most abundant in serum. Serum half-life is about 6 days.

CLINICAL SIGNIFICANCE 1. Selective IgA deficiency - Most common primary immunodeficiency. It is often asymptomatic. - Can cause recurrent sinopulmonary infections, GI infections (e.g., Giardia), and a higher risk of autoimmune disease (celiac disease) and atopy. - Cause: defective B-cell maturation into IgA-secreting plasma cells. - Anaphylactic transfusion reactions occur because patients form anti-IgA antibodies against donor IgA in blood products. Give washed red cells or IgA-deficient donor products. - Can give a false-negative result on celiac serology based on anti-tTG IgA. Check total IgA, or use IgG-based tests. - Can be associated with CVID. Ataxia-telangiectasia may also include IgA deficiency.

2. IgA nephropathy (Berger disease) - Most common primary glomerulonephritis worldwide. - Presents with episodic gross hematuria 1–3 days after an upper respiratory or GI infection (synpharyngitic), in contrast to the 1–3 week latency of poststreptococcal GN. - Biopsy: mesangial IgA deposits on immunofluorescence, with mesangial proliferation on light microscopy. Defective glycosylation (galactose-deficient IgA1) leads to immune complex formation.

3. IgA vasculitis (Henoch–Schönlein purpura) - Small-vessel leukocytoclastic vasculitis with IgA immune complex deposition. - Classic tetrad: palpable purpura on the buttocks and legs, arthralgias, abdominal pain (risk of intussusception, GI bleeding), and renal involvement. - Usually follows an infection in children and is self-limited.

4. Celiac disease and dermatitis herpetiformis - Celiac disease: anti-tissue transglutaminase IgA (best screening test) and anti-endomysial IgA. Duodenal biopsy shows villous atrophy and intraepithelial lymphocytes. - Dermatitis herpetiformis: pruritic grouped vesicles on extensor surfaces, with IgA deposits at dermal papillae. Treat with a gluten-free diet and dapsone.

5. Other - Linear IgA bullous dermatosis (vancomycin is a known drug trigger, with linear IgA at the basement membrane). - Multiple myeloma: IgA myeloma is the second most common type after IgG. - Waldenström macroglobulinemia is IgM, not IgA (a common mix-up). - Bacteria such as Neisseria, Haemophilus, and Streptococcus pneumoniae produce IgA protease to evade mucosal immunity.

HIGH-YIELD MEMORY AIDS - "IgA = Aa-Airway/mucosal; Appetizer (first line defense) in secretions." - Dimer + J chain + secretory piece; no complement fixation through the classical pathway. - IgG crosses the placenta, IgM is first to appear and is a pentamer, IgE mediates type I hypersensitivity and parasite defense, IgD is a B-cell surface receptor.