In a multi-institution study published in the Journal Clinical of Immunology, University of Utah researchers and colleagues have extended the spectrum of diseases caused by mutations in the RAG1 gene to include antibody deficiency diseases. They made the discovery after identifying a deficiency in RAG1 in two patients who were diagnosed with common variable immunodeficiency (CVID), an antibody deficiency disorder that leads to recurrent infections, such as pneumonia, and other complications. Antibodies, also known as immunoglobulins, identify and neutralize infectious agents, and a decrease in antibody production leads to infections.
Various mutations in the RAG1 gene already were know to cause a number of immune deficiencies, such as severe combined immunodeficiency and Omenn syndrome. RAG1-deficient patients are predicted to have high risk of life-threatening infections, therefore the identification of these mutations suggests treatments not usually considered for patients with CVID. The study shows that single-gene testing for most immunodeficiency diseases is not enough and that gene panels, exome sequencing and soon whole genome testing must be used to diagnose them, according to senior author Attila Kumánovics, M.D., of the ARUP Institute for Clinical and Experimental Pathology and assistant professor of pathology at the University of Utah.
The study's first author is David Buchbinder, of the Children’s Hospital of Orange County, Calif., and the National Institutes of Health.
View article in Journal of Clinical Immunology