Genetic variants shed light on kidney transplant rejection
Immunosuppressive medications help prevent organ rejection following transplantation, yet some patients still experience rejection despite receiving adequate treatment. New research from Yale, published in the Journal of Clinical Investigation, identifies a potential genetic mechanism underlying the increased risk in some patients of recent African ancestry, revealing changes in immune cell…
Genetic variants linked to kidney transplant rejection have been identified by researchers at Yale School of Medicine. The study, published in the Journal of Clinical Investigation, reveals that specific variations in the APOL1 gene could contribute to higher rejection rates among patients of recent African ancestry. These variants, G1 and G2, are more prevalent in self-reported African American individuals, who constitute 36% of dialysis patients in the U.S. population.
Although these variants initially evolved as a protective response against African sleeping sickness, their influence on the immune system persists, potentially heightening immune cell activity during kidney transplant rejection. Mice carrying the G1 or G2 variants displayed increased T cell activation, elevated immune cell infiltration into transplanted tissue, and diminished graft survival rates.
Notably, T cells with the G1 variant exhibited reduced responsiveness to calcineurin inhibition, a key target of immunosuppressive medications. While further research is necessary, these findings could pave the way for personalized immunosuppressive strategies, potentially benefiting patients with African ancestry.
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