The genetics of allergy and autoimmune diseases suggest shared disease pathways

Published online: February 7, 2017
There has been a parallel increase in allergic and autoimmune disorders in recent decades in “westernized” countries, suggesting shared etiologies. Similarly, shared environmental risk factors have been reported, such as birth by caesarian section. These observations are in apparent contrast to the understanding of allergy and autoimmune diseases as distinct immunologic disorders with counteracting underlying immune mechanisms and to the observations in some studies of a lower incidence of allergy among patients with autoimmune disease.

In an original article recently published in The Journal of Allergy & Clinical Immunology (JACI), Kreiner and colleagues took a genetic approach to understanding the relationship between allergy and autoimmune diseases. They combined information on known risk variants for autoimmune diseases with genetic data from more than 60,000 subjects with and without allergy and used this to investigate shared risk variants, genetic pathways, and regulatory mechanisms.

The authors found that a substantial number of genetic variants were associated with both autoimmune diseases and allergy. Interestingly, many of these variants showed the same direction of effect (same allele associated with higher risk of both allergy and autoimmune disease) while others showed opposite direction of effect (the allele associated with increased risk of allergy was associated with decreased risk of autoimmune disease). In addition, allergy and autoimmune disease variants had shared immune pathways within regulatory regions in immune cells, which were distinct from other diseases.

The authors hypothesized that identifying shared genetic mechanisms might increase our understanding of allergy and autoimmune disease and their complex relationship. For example, shared variants could identify important “vulnerable” points in immune system pathways that may be affected by environmental exposures or other modifiers of disease risk. In particular the shared variants with same direction of effect might thereby provide important clues for understanding the parallel epidemics of these diseases and thereby facilitate future strategies for disease prevention.

