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

Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Australia.
AIDS (Impact Factor: 5.55). 11/2002; 16(15):2043-7. DOI: 10.1097/00002030-200210180-00009
Source: PubMed


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.
DNA samples from patients with a range of IRD were typed for polymorphic loci in genes encoding immune-mediators.
PCR-restriction fragment length polymorphism assays were used to type loci in the and genes. Alleles of a microsatellite in the CD30 promoter were determined by capillary electrophoresis.
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 and showed no distinct patterns.
Distinct cytokine-mediated mechanisms contribute to IRD initiated by herpesvirus and mycobacterial infections.

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    • "IL-12 and IL-18 influence the induction of Th1 cytokine responses. Carriage of IL12B (3' UTR)*C was more common in Caucasian HIV-positive patients without neuropathy [9] and without CMV retinitis experienced after commencement of ART [10], suggesting a protective role in both cases. "
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    • "However, our report is relatively low as compared with studies done in Thailand and Texas. Our low rate of MTB infection might be explained partly due to genetic polymorphism and racial differences of the study subjects [23]. And the nature of retrospective studies that may result differences in documenting and interpreting data in different settings also might play a role in variation of IRD reports. "
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