Human interleukin-2 receptor {beta} mutations associated with defects in immunity and peripheral tolerance

We report three homozygous mutations in the IL2RB gene of eight individuals from four consanguineous families that cause disease by distinct mechanisms. Nearly all patients presented with autoantibodies, hypergammaglobulinemia, bowel inflammation, dermatological abnormalities, lymphadenopathy, and cytomegalovirus disease. Patient T lymphocytes lacked surface expression of IL-2Rβ and were unable to respond to IL-2 stimulation. By contrast, natural killer cells retained partial IL-2Rβ expression and function. IL-2Rβ loss of function was recapitulated in a recombinant system in which IL2RB mutations caused reduced surface expression and IL-2 binding. Stem cell transplant ameliorated clinical symptoms in one patient; forced expression of wild-type IL-2Rβ also increased the IL-2 responsiveness of patient T lymphocytes in vitro. Insights from these patients can inform the development of IL-2–based therapeutics for immunological diseases and cancer.

Source: The Journal of Experimental Medicine - June 2, 2019 Category: Internal Medicine Authors: Zhang, Z., Gothe, F., Pennamen, P., James, J. R., McDonald, D., Mata, C. P., Modis, Y., Alazami, A. M., Acres, M., Haller, W., Bowen, C., Döffinger, R., Sinclair, J., Brothers, S., Zhang, Y., Matthews, H. F., Naudion, S., Pelluard, F., Alajlan, H. Tags: Autoimmunity, Immunodeficiency, Human Disease Genetics Articles Source Type: research