IgA exists in serum in both monomeric and dimeric forms, comprising approximately 15% of the total serum Ig. Secretory IgA, a dimer, provides the primary defense mechanism against some local infections because of its abundance in mucosal secretions (e.g., saliva and tears). The principal function of secretory IgA may be not to destroy antigens but to prevent passage of foreign substances into the circulatory system.
Properties of IgA:
- Molecular weight: 320,000 (secretory)
- H-chain type (MW): alpha (55,000)
- Serum concentration: 1 to 4 mg/mL
- Percent of total immunoglobulin: 15%
- Glycosylation (by weight): 10%
- Distribution: intravascular and secretions
- Function: protect mucus membranes
The role of IgA in the immune response
IgA comprises approximately 15% of all immunoglobulins in healthy serum. Two IgA subtypes exist in humans, IgA1 und IgA2, while mice have only one subclass. They differ in the molecular mass of the heavy chains and in their concentration in serum.
IgA in serum is mainly monomeric, but in secretions, such as saliva, tears, colostrums, mucus, sweat, and gastric fluid, IgA is found as a dimer connected by a joining peptide. Most IgA is present in secreted form. This is believed to be due to its properties in preventing invading pathogens by attaching and penetrating epithelial surfaces. IgA is a very weak complement-activating antibody; hence, it does not induce bacterial cell lysis via the complement system. However, secretory IgA works together with lysozymes (also present in many secreted fluids), which can hydrolyze carbohydrates in bacterial cell walls thereby enabling the immune system to clear the infection. IgA is predominantly found on epithelial cell surfaces where it acts as a neutralizing antibody.
IgA deficiency in disease
The most prevalent antibody defect is a selective IgA deficiency (SIgAD). Alterations in IgA1/IgA2 ratio often go hand in hand with specific disease states, such as recurring infections of the airways or a kidney disorder called IgA nephropathy.
There are various severe health conditions that can lead to low levels of Immunoglobulin A in the body, one of which is gonorrhea. The bacteria that cause gonorrhea produce an enzyme that splices IgA antibodies into Fc and Fab fragments. The Fab part still can recognize the bacteria, but without the Fc fragment, attachment to phagocyting cells is not possible. When the body does not have sufficient quantities of IgA, the person may be diagnosed with selective IgA deficiency.
Patients suffering from selective IgA deficiency can have normal levels of the other antibodies, fully functioning T-cells, phagocytes, and other components of the immune system. Patients who suffer from a selective IgA deficiency are more prone to autoimmune disorders like rheumatoid arthritis, lupus, allergies and asthma.
IgA1 comprises approximately 85% of total IgA concentration in serum. Although IgA1 shows a broad resistance against several proteases, there are some that can affect/splice on the hinge region. IgA1 shows a good immune response to protein antigens and, to a lesser degree, polysaccharides and lipopolysaccharides.
IgA2, representing only up to 15% of total IgA in serum, plays a crucial role in the mucosa of the airways, eyes and the gastrointestinal tract to fight against polysaccharide and lipopolysaccharide antigens. It also shows good resistance to proteolysis and many bacterial proteases, supporting the importance of IgA2 in fighting bacterial infections.