Introduction to IgA
In human, the content of IgA in serum is second only to IgG, accounting for 10-20% of the total immunoglobulins, and has a unique role in mediating immunity. IgA is a polyvalent antibody, which is abundant in mucosal secretions. As the first line of defense against infection, IgA is the main defense mechanism for mucosal infections. Secretory IgA functions to prevent foreign substances from entering the circulatory system, rather than to destroy antigens.
Structure of IgA
The monomeric structural unit of IgA comprises two identical heavy chains and two identical light chains arranged into two Fab regions and an Fc region, separated by a flexible hinge region. The heavy and light chains fold up into globular domains. IgA mainly exists in the form of dimers in secretions, and sIgA is formed by the polymerization of two or more IgA monomers. A typical sIgA is mainly composed of two IgA monomers, a J chain, and a secretory component. The secretory component is a 75 kDa polypeptide chain synthesized by intestinal epithelial cells, which acts as a dimer IgA-specific receptor for binding to the dimer form of IgA. The total molecular weight of IgA antibodies is approximately 160 kDa.
Fig. 1 The structure of IgA in its monomeric form and dimeric form. (Odineal, 2020)
Classification of IgA
There are two isotypes of IgA, IgA1 and IgA2, both of which are highly glycosylated proteins. The proportion of IgA1 and IgA2 secretory cells in different lymphoid tissues is different
- IgA1. IgA1 is dominant in serum, accounting for 85% of the total IgA concentration in serum. IgA1 shows broad resistance to several proteases, but some can affect or splice on the hinge region. IgA1 shows a good immune response to protein antigens, but a low degree of immune response to polysaccharides and lipopolysaccharides.
- IgA2.IgA2 accounts for only 15% of the total IgA in serum, and it mainly exists in the mucous membranes of the airways, eyes, and gastrointestinal tract to combat polysaccharides and lipopolysaccharide antigens. It also shows excellent resistance to proteolysis and many bacterial proteases, and plays an important role in fighting bacterial infections.
According to the location of IgA, it can be divided into two types: serum IgA and secretory IgA.
- Serotype IgA. Serotype IgA exists in the serum, and it has certain immune functions of IgG and IgM. Specific IgA can neutralize antigens in the blood.
- Secretory IgA. Secretory IgA is present in secreted fluids, such as saliva, tears, and milk. Secreted IgA is the main antibody of the local mucosal anti-infection immunity. Therefore, it is also called mucosal immune antibody.
Application of IgA
IgA is the first line of defense against infection by inhibiting the adhesion of bacteria and viruses to epithelial cells, and neutralizing bacterial toxins and viruses both extracellular and intracellular. The application of IgA including the followings:
- For disease therapy. IgA antibodies show great promise in the treatment of cancers, infectious diseases, inflammations, and allergic diseases. At present, many IgA antibodies have been used clinically and achieved good results.
- For diagnosis. Detection of IgA content has important clinical significance. It can help to understand the body's humoral immune function status and help diagnose various diseases such as immune hyperplasia, immune deficiency, infection, and autoimmunity.
- For vaccine development. sIgA plays a key role in regulating infections caused by viruses or bacteria, indicating that it has the potential for vaccine development to prevent human infections from various diseases.
- Kumar N, et al. (2020). "Structure of the secretory immunoglobulin A core." Science. 367.6481: 1008-1014.
- Pavlou A K. and Mark J. B. (2005). "The therapeutic antibodies market to 2008." European Journal of Pharmaceutics and Biopharmaceutics. 59.3: 389-396.
- Odineal, D.D.; and Gershwin, M.E. The Epidemiology and Clinical Manifestations of Autoimmunity in Selective IgA Deficiency. Clin Rev Allergy Immunol. 2020, 58(1): 107-133.
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