Immunoglobulin A (IgA)

Introduction

Immunoglobulin A (IgA), also referred to as sIgA in its secretory form, is an antibody critical to the immune function of mucous membranes. It is the most abundantly produced antibody in mucosal tissues, surpassing all other antibody types combined. Daily, between three and five grams of IgA are secreted into the intestinal lumen, accounting for up to 15% of total immunoglobulins in the body.

Structure and Subclasses

IgA exists in two subclasses:

• IgA1: Predominates in serum (~80%) and features an extended hinge region for flexibility.
• IgA2: More prevalent in secretions (~35%) and lacks disulfide bonds between heavy and light chains, relying on non-covalent bonds.

Forms of IgA:

• Monomeric: Found in serum.
• Dimeric (Polymeric): The predominant form in secretions, bound to the J-chain and secretory component, forming secretory IgA (sIgA).

Functions of IgA

1. Mucosal Immunity:

   • Neutralizes pathogens in mucous secretions (e.g., tears, saliva, colostrum).
   • Prevents microbial adherence to epithelial cells through steric hindrance and immune exclusion.

2. Anti-Inflammatory Role:

   • Inhibits inflammatory effects of other immunoglobulins.
   • Poor activator of the complement system and weak opsonization.

3. Protection in Harsh Environments:

   • The secretory component shields IgA from proteolytic degradation in the gastrointestinal tract.

Production and Transport

• Plasma Cells: Produce polymeric IgA in the lamina propria.
• Epithelial Cells: Express the polymeric immunoglobulin receptor (pIgR) to transport IgA across mucosa.
• sIgA Formation: pIgR-bound IgA is endocytosed, secreted into the lumen, and cleaved to release sIgA.

Clinical Significance

Disorders:

• Selective IgA Deficiency: Inherited inability to produce IgA, leading to immunodeficiency.
• IgA Nephropathy: Kidney disease caused by IgA deposits.
• Henoch–Schönlein Purpura (HSP): Systemic vasculitis with IgA and C3 deposits in small vessels.

Autoimmune Links:

• Celiac Disease: Associated with IgA anti-endomysial antibodies and transglutaminase autoantibodies.
• Linear IgA Bullous Dermatosis: IgA-mediated blistering disorder.

Pathogen Evasion

Microbes like Neisseria gonorrhoeae, Streptococcus pneumoniae, and Haemophilus influenzae produce IgA proteases to degrade IgA and evade immunity.

FAQs

1. What is the primary role of IgA?

IgA defends mucous membranes by neutralizing pathogens and preventing their attachment to epithelial cells.

2. How does secretory IgA differ from serum IgA?

• Serum IgA: Mostly monomeric.
• Secretory IgA: Dimeric with a J-chain and secretory component, resistant to enzymatic degradation.

3. What causes IgA deficiency?

Genetic mutations impair IgA production, increasing susceptibility to infections and autoimmune disorders.

4. Why is IgA important in gut health?

It agglutinates pathogens in the mucus layer, facilitating their removal via peristalsis.

5. Can IgA activate the complement system?

Weakly; it primarily uses the alternative and lectin pathways.

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References

• Key studies from Mucosal Immunology, Nature Reviews Immunology, and Journal of Clinical Immunology.
• For further reading: IgA at MeSH.

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