An X-linked Gene Associated with Autoimmune Disorders

October 6, 2021

An exciting new discovery from researchers at Harvard Medical School has provided new insight into the possible cause of some autoimmune disorders. Autoimmune diseases are among the most common afflictions of humans, yet their root causes are not known.  Most arise spontaneously or sporadically in people without a clear genetic linkage or heritability.  Diseases such as systemic lupus erythematosus are found primarily in women with an approximate 9:1 female:male ratio.  The laboratory of Richard D. Cummings, Ph.D. and Junwei Zeng, Ph.D. in the Department of Surgery at Beth Israel Deaconess Medical Center discovered that mutations of the X-linked gene Cosmc, which they engineered in the B cells of mice, result in a full-blown autoimmune phenotype that has a strong female-bias similar to that seen in lupus.  Cosmc encodes a molecular chaperone that is a master regulator of protein glycosylation.  The engineered mice with such altered glycosylation of their B cells display many hallmarks of human autoimmune diseases, including female bias, antinuclear antibodies, skin lesions, weight loss, splenomegaly, hypergammaglobulinemia, ocular involvement, kidney involvement, and circulating immune complexes in blood. The researchers found that, in terms of mechanism, a major dysfunction occurs in the B cell receptor complex, which has previously been linked to human autoimmune diseases.  This exciting breakthrough is leading the team to explore the possible relationship of Cosmc and B cell glycosylation to human autoimmune disorders.  This research was just published in Science Advances, a peer-reviewed open-access scientific journal published by the American Association for the Advancement of Science.

Citation:  Zeng et al., Sci. Adv. 2020; 7: eabg9118
DOI: 10.1126/sciadv.abg9118