An infant was suffering from inflammatory bowel disease, eczema, food allergies, lung disease, and persistent cytomegalovirus (CMV) infection. His older sister was experiencing similar problems. The scientific investigation of their cases led researchers from the University of Colorado Anschutz Medical Campus to discover a new immunodeficiency disease that is caused by a single genetic mutation. Their findings were published last week in The Journal of Experimental Medicine.
The siblings’ symptoms were consistent with an immune dysregulation syndrome, which can lead to an increased cancer risk. Upon closer examination, researchers discovered a defect in a gene called IL2RB (encoding interleukin-2 receptor beta, IL-2R?), which causes a decrease in the number of immune cells (regulatory T cells) that prevent autoimmunity. These two children are the first known humans to have this genetic defect.
In addition to a decreased number of regulatory T cells, the siblings also had an accumulation of “natural killer” cells. When functioning correctly, natural killer cells protect against viral infections and cancer. However, in a press release from the University of Colorado medical campus, co-author Elena Hsieh, MD explains that “the mutation meant that the natural killer cells were incapable of maturing properly and could not clear CMV, resulting in persistent and debilitating infection.”
Hsieh emphasizes the rarity of tracking down a disease to a single gene; especially since there were not any documented cases of mutations in this gene that can lead to human disease. Co-author Cullen Dutmer, MD believes that others may likely suffer from this condition, but it hasn’t been identified. In the press release he states that “although clearly a rare disease, it has likely been missed in other children. Now that it is out there, we know to look for it.”
Researchers are hopeful that this genetic defect can be treated with gene therapy. Co-author Ross Kedl, Ph.D., suggests that “we could feasibly go in, manipulate the gene, and get it back in the right sequence.” Gene therapy is becoming a more viable treatment option with recent advances in identifying genetic causes of immunodeficiency diseases. Dutmer and Hsieh are hopeful that once a genetic cause is identified “that would allow for therapeutic interventions that are uniquely tailored to meet the need of the individuals.”