Polymorphisms in cytokine genes define subpopulations of HIV-1 patients who experienced immune restoration diseases.
ABSTRACT 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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ABSTRACT: INTRODUCTION: Animal and in vitro models of HIV-associated sensory neuropathy suggest an inflammatory etiology. Previous genetic association studies of HIV-SN have been in small Caucasian or Asian cohorts. We assessed cytokine single nucleotide polymorphisms (SNPs) in a Black Southern African cohort. METHOD: 342 black HIV-positive Southern Africans were recruited. 190 individuals had HIV-associated sensory neuropathy and 152 did not. DNA samples from all participants were genotyped for cytokine SNPs identified in studies of HIV disease and/or neuropathy. RESULTS: IL4-590*T associated with an increased prevalence of HIV-SN including following correction for age, height and CD4 T-cell count. No other cytokine SNPs assessed displayed an association. DISCUSSION: We identified a novel association between IL4-590*T and HIV-SN in African HIV-positive patients which warrants further investigation.Molecular Immunology 03/2013; DOI:10.1016/j.molimm.2013.02.002 · 3.00 Impact Factor
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ABSTRACT: The immune reconstitution inflammatory syndrome (IRIS) represents a diverse range of immunopathologic reactions resulting in clinical deterioration that may occur as immune function is partially restored in HIV-infected patients receiving highly active antiretroviral therapy. Approximately half of IRIS events are dermatologic, and dermatologic IRIS is described in relation to a wide range of conditions, the commonest being herpes zoster and herpes simplex. Most cases of IRIS result in mild and moderate symptoms, but non-dermatologic manifestations related to IRIS have resulted in death. This article covers certain general issues related to IRIS and then focuses on the spectrum of dermatologic manifestations.Dermatologic Clinics 11/2006; 24(4):549-70, vii. DOI:10.1016/j.det.2006.06.007 · 1.43 Impact Factor
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ABSTRACT: We report a case of a cervical intraepithelial neoplasia associated with epidermodysplasia verruciformis human papillomavirus (HPV) type 5 and HPV type 16 in a human immunodeficiency virus-infected patient. Furthermore, epidermodysplasia verruciformis-like cutaneous eruptions after initiation of highly active antiretroviral therapy has never been described as a manifestation of an immune restoration syndrome.European journal of dermatology: EJD 03/2007; 17(2):149-52. DOI:10.1684/ejd.2007.0129 · 1.95 Impact Factor