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

J Infect Dis. 2023 Jul 14;228(2):111-115. doi: 10.1093/infdis/jiad059.

Abstract

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. Clinical Trials Registration. NCT00286767, NCT02147405.

Keywords: genetics; hemophagocytic lymphohistiocytosis; immune reconstitution inflammatory syndrome; mycobacteria; tuberculosis.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • Humans
  • Immune Reconstitution Inflammatory Syndrome*
  • Lymphohistiocytosis, Hemophagocytic* / complications
  • Lymphohistiocytosis, Hemophagocytic* / genetics
  • Tuberculosis* / complications
  • Tuberculosis* / drug therapy
  • Tuberculosis* / genetics

Associated data

  • ClinicalTrials.gov/NCT00286767
  • ClinicalTrials.gov/NCT02147405