Polymorphisms in cytokine genes define subpopulations of HIV-1 patients who experienced immune restoration diseases

Objective: To further elucidate the immunopathogenesis of immune restoration diseases (IRD) in HIV patients responding to antiretroviral therapy and determine whether IRD associated with different opportunistic pathogens involve distinct immunopathological mechanisms. Design: DNA samples from patients with a range of IRD were typed for polymorphic loci in genes encoding immune-mediators. Methods: PCR-restriction fragment length polymorphism assays were used to type loci in the IL1A, IL1B, IL6, TNFA and IL12B genes. Alleles of a microsatellite in the CD30 promoter were determined by capillary electrophoresis. Results: Only 8% of patients with IRD associated with a herpesvirus infection carried IL12B-3'UTR*2, compared with 42-54% of patients with other or no IRD. Patients with IRD arising from mycobacterial infection rarely carried IL6-174*C (36% versus 61-71%) and never carried TNFA-308*2 (0% versus 23-52%). TNFA-308*2 was carried by 52% of patients who experienced IRD associated with a herpesvirus infection, as several patients with exacerbations of cytomegalovirus retinitis carried this as part of a HLA-A2,B44 haplotype. Polymorphisms in IL1A, IL1B and CD30 showed no distinct patterns. Conclusions: Distinct cytokine-mediated mechanisms contribute to IRD initiated by herpesvirus and mycobacterial infections. (C) 2002 Lippincott Williams Wilkins.