Immunoglobulins: IgA

Optimal Takeaways

Immunoglobulin A is the primary immunoglobulin that protects epithelial surfaces and is secreted in the GI tract, tears, saliva, and colostrum and can be measured in the blood. Low IgA may be seen in celiac disease and other autoimmune disorders. High IgA may be associated with chronic infection, liver disease, inflammation, and metabolic dysfunction.

Standard Range: 47 – 310 mg/dL (0.47 – 3.10 g/L)

The ODX Range: 81 - 310 mg/dL (0.81 - 3.10 g/L)

Low IgA can occur with hypoproteinemia, congenital deficiency, ataxia, immune suppression, and immunosuppressive drugs, including dextran and steroids (Pagana 2021).

Selective IgA deficiency, the most common immunodeficiency disorder, is characterized by recurrent infection and increased risk of autoimmune disease and atopy. Low IgA may be associated with chronic diarrhea as well (Justiz 2021).

High levels of IgA can occur in chronic liver disease, chronic infection, inflammatory bowel disease, and use of certain drugs including certain medications including phenytoin, hydralazine, isoniazid, procainamide, tetanus toxoid/antitoxin, and gamma globulin (Pagana 2021). Higher levels of serum IgA may be associated with hyperglycemia, hypertriglyceridemia, obesity, abdominal obesity, metabolic syndrome, inflammation, and alcohol excess. Levels may increase with aging and tend to be higher in males than females (Gonzalez-Quintela 2008).

Overview

IgA accounts for 15% of all immunoglobulins in the body and is found in the gastrointestinal tract, respiratory tract, tears, saliva, colostrum, and blood (Pagana 2019). It is the primary antibody released in secretions, and it protects epithelial surfaces. IgA activates the alternative pathway of the complement system (Justiz 2021). Elevated levels of IgA (and IgG) may parallel increases in inflammatory IL-6, a cofactor in the synthesis of immunoglobulins. Serum IgA levels increase as alcohol intake increases (Gonzalez-Quintela 2008).

Selective IgA deficiency can be seen in celiac disease, complicating the serological evaluation of the condition. In one retrospective cohort study, IgA deficiency was diagnosed when total serum IgA was below 6 mg/dL, while partial IgA deficiency was diagnosed in adults with IgA below 70 mg/dL. Adults with either degree of IgA deficiency were significantly more likely to have a concomitant autoimmune disorder such as Hashimoto’s thyroiditis, Graves’ disease, type 1 diabetes, Sjogren syndrome, vitiligo, psoriasis, Addison’s disease, or autoimmune neuropathy (Chow 2012).

A prospective study of 1,000 individuals being worked up for celiac disease found that autoimmune disease was significantly higher in celiacs with low IgA than those with normal IgA (67% versus 23%). Autoimmune disorders included Hashimoto’s, rheumatoid arthritis, and autoimmune hepatitis (Pallav 2016).

References

Chow, Marisa A et al. “Immunoglobulin A deficiency in celiac disease.” Journal of clinical gastroenterology vol. 46,10 (2012): 850-4. doi:10.1097/MCG.0b013e31824b2277

Dunkelberger, Jason R., and Wen-Chao Song. "Complement and its role in innate and adaptive immune responses." Cell research 20.1 (2010): 34-50.

Justiz Vaillant, Angel A., et al. “Immunoglobulin.” StatPearls, StatPearls Publishing, 12 October 2021.

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Pallav, Kumar et al. “Immunoglobulin A deficiency in celiac disease in the United States.” Journal of gastroenterology and hepatology vol. 31,1 (2016): 133-7. doi:10.1111/jgh.13176

Gonzalez-Quintela, A et al. “Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities.” Clinical and experimental immunology vol. 151,1 (2008): 42-50. doi:10.1111/j.1365-2249.2007.03545.x