Mycobacterial Immune Reconstitution Inflammatory Syndrome in HIV is Associated With Protein-Altering Variants in Hemophagocytic Lymphohistiocytosis-Related Genes

People with HIV (PWH) and mycobacterial infections can develop immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy. The pathophysiology of mycobacterial-IRIS overlaps with primary hemophagocytic lymphohistiocytosis (pHLH). To assess possible genetic predisposition to IRIS, protein-altering variants in genes associated with HLH were evaluated in 82 PWH and mycobacterial infections who developed IRIS (n = 56) or did not develop IRIS (n = 26). Protein-altering variants in cytotoxicity genes were found in 23.2% of IRIS patients compared to only 3.8% of those without IRIS. These findings suggest a possible genetic component in the risk of mycobacterial IRIS in PWH.

Automated summary

People with HIV and mycobacterial infections may develop immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy. The pathophysiology of mycobacterial-IRIS overlaps with primary hemophagocytic lymphohistiocytosis (pHLH). By evaluating protein-altering variants in genes associated with HLH, it was found that 23.2% of IRIS patients had these variants, compared to only 3.8% of those without IRIS. These findings suggest a possible genetic component in the risk of mycobacterial IRIS in people with HIV and mycobacterial infections.