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Immunoglobulin A



See also: Antibody, immunoglobulins

  • Secreted as dimer, with J (joining) chain between mononer substituents
  • Most important secretory antibody, capable of passing across epithelial cell layers (transcytosis)
  • Secreted in mother's milk to child
  • Huge amounts are secreted in the GI tract each day (~10g per day)
  • sIgA-secreting plasma B cells interact with poly-Ig receptors on basalateral surfaces of mucosal cells, especially those close to the GI tract lumen

IgA represents about 15% to 20% of immunoglobulins in the blood, although it is primarily secreted across the mucosal tract into the stomach and intestines. It is also found in maternal milk, tears and saliva. This immunoglobulin helps to fight against pathogens that contact the body surface, are ingested, or are inhaled. It does not activate complement, and opsonises only weakly. Its heavy chains are of the type α. It exists in two forms, IgA1 (90%) and IgA2 (10%) that differ in the structure. IgA1 is composed like other proteins, however in IgA2 the heavy and light chains are not linked with disulfide but with noncovalent bonds. Though IgA2 is less in serum, it accounts for major secretory antibody.

The IgA found in secretions have a special form. They are dimeric molecules, linked by two additional chains. One of these is the J chain (from join), which is a polypeptide of molecular mass 1,5 kD, rich with cysteine and structurally completely different from other immunoglobulin chains. This chain is formed in the antibodies secreting cells. The dimeric form of IgA in the outer secretions has also a polypeptide of the same molecular mass (1,5 kD) that is called the secretory chain and is produced by the epithelial cells. It is also possible to find trimeric and even tetrameric IgA.

Decreased or absent IgA, termed selective IgA deficiency, can be a clinically significant immunodeficiency. Secretory IGA is typically depressed in non-secretors.


The role of IgA is closely related to the potential for gut related health problems. Ig-A is most commonly used by the body to "soak up" allergic substances from the digestive tract. It is usually evenly distributed throughout the gut tissue except in specialized lymphoid areas where large amounts are manufactured and encapsulated. Lymphoid tissue is found in those areas where immune activity is constantly required, such as the appendix, tonsils and Peyer's Patches of the intestines, areas which routinely become inflamed. IgA has two major functions. The first is to cause bacteria and allergic substances to stick to the mucus membranes. The second is to turn on the alternative complement pathway to destroy them. Improper function or secretion of IgA has been implicated in a variety of immune complex disorders including systemic lupus erythematosis and phlebitis.

IgA is often found with gut mucus, usually with one end of the immunoglobulin tailored to adhere to and anchor with the mucus lining and the other, "business end" of the molecule projecting out into the gut ready for immune reactions if necessary. Calculations suggest that up to 50g of IgA may be synthesized by the gut daily, a mass equivalent to the immunoglobulin producing tissue of the spleen. Most B lymphocytes at the external mucosa are dedicated to IgA synthesis and form a recirculating pool of cells that home preferentially back to mucosal sites. Antigens present in the small intestine are sampled by a special type of cell, called an [M cell]?, located over each Peyer's patch and bordering on the intestinal lumen. The antigens are transferred to an environment of immune cells, accessory antigen presenting cells, and regulatory T cells within the patch.

After antigen stimulation, precursors of IgA plasma cells migrate via the lymphatics to the blood, the spleen and the liver; then they return to the gut or localize at distant mucosal sites. Several factors have been postulated to explain the accumulation of potential IgA producing cells at these specialized sites. The mucosal environment, rich in microbial antigens and mitogens is known to influence the immune specificity of lymphocytes in mucosal tissue. T cells have been described that act on surface IgA positive B cells to increase or suppress IgA synthesis. When foreign material attempts to pass through the gut wall, IgA binds to it and forms an immune complex. Immune complexes are destroyed right at the site of attachment to IgA in the gut wall or transported to the liver and cleared by [Kuppfer cells]?.

Insufficient IgA production is a common immunodeficiency (it is genetically produced in 1 of 600 individuals of European origin, and can result from dietary imbalance, tonsillectomy or appendectomy). If there is insufficient IgA in the tissues to bind with microbes or allergic particles, they will pass into the portal circulation and liver. If the liver is incapable of dealing with the immune complexes coming from intestinal absorption, they will pass into the systemic circulation and stimulate a general immune response. Allergic disorders and auto immunity occur with undue frequency in the milder forms of IgA deficiency. The former comprises reaginic IgE type) allergy in general and food sensitivity, especially gluten-sensitive malabsorption, in particular. The frequency of auto antibodies in IgA deficiency remains a riddle. Perhaps they appear as a result of excessive absorption of foreign material cross-reacting with self-substances, e.g. reticulin?; alternatively they may be the hallmarks of slow virus infections made possible by the failure of the gut barrier.

IgA class antibodies are not found in very high concentrations in the blood. Rather, it is found very commonly on the mucosal surfaces of the body. Typically IgA is bound to the mucus at one end, with the free, or business end, sticking freely out.IgA is found abundantly in saliva, tears and breast milk (especially colostrum) and is the primary defense at mucosal surfaces such as bronchioles of the lungs, the nasal passages, prostate, vagina, and intestine. It normally guards against bacterial and viral infections.

IgA deficiency is the most commonly seen immune deficiency. The deficiency is lifelong and precautions need to be taken to prevent infections. In general, IgA Deficiency occurs once in every 400 to 2,000 individuals. However, its incidence varies across racial and ethnic lines. Many IgA-deficient patients are healthy, with no more than the usual number of infections. Others may typically suffer with recurrent ear, sinus, or lung infections that may not respond to standard courses of antibiotics. These patients can have an increased frequency of allergies, asthma, chronic diarrhea (often due to parasite), and autoimmune diseases.

IgA and secretor status

In tests on 202 Caucasians, IgA levels were found to be significantly lower in non-secretors than in secretors. This probably helps to explain why non-secretors have higher incidences of rheumatic heart disease and chronic kidney disease (glomerulonephritis) over non-secretors: The lower levels of IgA cannot prevent microorganisms from gaining access to the blood stream from the oral cavity and digestive tract.

IgA and antibodies to dietary lectins

In a study looking at subjects with kidney problems (nephropathy) resulting from autoimmune disease and deposition of immune complexes in the kidney’s filtration system, anywhere from 19% to 38% (depending on the nationality of the subjects studied) had antibodies against common dietary lectins, which was significant in that none of the healthy controls had any such antibodies.

  • Coppo R;Amore A;Roccatello D;Gianoglio B;Molino A;Piccoli G;Clarkson AR;Woodroffe AJ;Sakai H;Tomino Y. IgA antibodies to dietary antigens and lectin-binding IgA in sera from Italian, Australian, and Japanese IgA nephropathy patients. American Journal Of Kidney Diseases, Vol 17 No 4(April), 1991: pp. 480-7

ABO blood groups and secretory IgA variance in breast milk

Arch Dis Child Fetal Neonatal Ed 1994 Nov;71(3):F192-F197

IgA antibodies in human milk: epidemiological markers of previous infections?

Nathavitharana KA, Catty D, McNeish AS Institute of Child Health, University of Birmingham.

  • The concept of an enteromammary link in secretory IgA (SIgA) antibody production was tested by hypothesising that specific SIgA antibody profiles in human milk might be an epidemiological marker for enteropathogens in a community. Milk from three subject groups was studied: 64 Sri Lankan women living in poor suburbs of Colombo, 20 Asian immigrant women domiciled in Birmingham, for a median period of five years (range 14 days-16 years), and 75 white women living in Birmingham. The number of Sri Lankan and Asian immigrant women with SIgA antibodies to all 14 diarrhoeagenic E coli antigens (except O127 in Asian women) was significantly higher than in the white controls. The amount of E coli O antigen specific SIgA antibody activity as a percentage of total SIgA also gave significantly higher median values in Sri Lankan (6%) and in Asian immigrant (4%) women than in white controls (0.7%). SIgA antibodies were highly O serogroup specific and showed excellent concordance between crude O and the corresponding purified lipopolysaccharide antigens. These results suggest that milk antibody profiles represent an epidemiological marker of exposure to enteral pathogens. The continuing specific milk antibody response in Asian women who have been domiciled in the United Kingdom for many years may indicate 'memory' in the human secretory immune system.
Dietary antigens and primary immunoglobulin A nephropathy

J Am Soc Nephrol 1992 Apr;2(10 Suppl):S173-S180 Coppo R, Amore A, Roccatello D Nephrology and Dialysis Department, Regina Margherita Children's Hospital, Turin, Italy.

  • To investigate the role of dietary components in immunoglobulin A mesangial nephropathy (IgAGN), this study focused on gliadin, based on the reported association between coeliac disease and IgAGN as well as the pilot observation that a gluten-free diet was able to reduce the levels of circulating IgA immune complexes (IgAIC). Several gluten lectinic fractions modulate leukocyte oxidative metabolism, cytotoxicity, and chemotaxis. In IgAGN patients, serum IgA to dietary Ag were sporadically positive and IgAIC containing IgA to dietary components were significantly increased. The affinity of serum IgA to various lectins was increased in some patients. A gluten-free diet, given to IgAGN patients with high levels of circulating IgAIC and positive antigliadin IgA, was followed by a decrease in the mean levels of both IgAIC and IgA to various dietary Ag, parallel to a reduction in proteinuria. These data suggest that dietary components, such as Ag or lectins, may play a role in IgAGN by promoting IgAIC formation and perhaps favoring mesangial localization via lectinic interactions.


  • D'Adamo, P. Gut Ecosystems I. Townsend Letter For Doctors, Port Washington WA, 1989