Immunoglobulin (Ig)


IgA

Fundamental roles: Neutralizing antibody - preventing invading pathogens by attaching and penetrating epithelial surfaces.  A very weak complement activating antibody.

Presence in serum: approximately 15% of all immunoglobulins in healthy serum.

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 their 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, gastric fluid, IgA is found as a dimer where they are 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 just 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 hydrolyze carbohydrates in bacterial cell walls enabling the immune system to clear the infection. IgA which is predominantly found on epithelial cell surfaces where it acts as a  neutralizing antibody.

IgA Deficiency and Diseases

The most prevalent antibody defect is a selective IgA deficiency (SIgAD). Alterations in IgA1/IgA2 ratio very 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 such as gonorrhea. The bacteria leading to gonorrhea produce an enzyme leading to the splicing of IgA antibodies into the Fc and Fab fragment. 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 Immunoglobulin A 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.

IgA Subclasses

IgA1

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, to polysaccharide and lipopolysaccharides.

IgA2

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 lipopolysaccaride antigens. It also shows good resistance to proteolysis and many bacterial proteases, supporting the importance of IgA2 in fighting bacterial infections.