title: MHC haplotypes affect the expression of opportunistic infections in HIV patients.
abstract: This study explores whether MHC genes affect manifestations of opportunistic infections in HIV patients not treated with highly active antiretroviral therapy (HAART) and immunopathologic responses to pre-existing infections in patients who achieved immune reconstitution following HAART (i.e., "immune restoration diseases" or IRD). HLA-B27 and B17 were relatively rare in all HIV patients, but no HLA-B alleles significantly affected cytomegalovirus (CMV) or Mycobacterium avium complex (MAC) disease in patients who had not received HAART. However coexpression of alleles previously defined as the 44.1 ancestral haplotype (HLA-A2, -B44, and -DR4) was more common in the MAC and CMV patients. After HAART, HLA-B44 and (HLA-A2, -B44, -DR4) were found in 66% and 33%, respectively, of patients who experienced an IRD manifested as CMV retinitis and/or encephalomyelitis. This was confirmed by examination of microsatellite alleles, where the C1_2_5 locus in the class I region was most concordant with the 44.1 haplotype in the patients. HLA-B44 was not associated with IRD initiated by Mycobacterium sp, cutaneous VZV or HSV, or HCV infections, suggesting distinct pathologic mechanisms are responsible. CMV retinitis/encephalomyelitis IRD patients had marginally lower pretreatment CD4 T-cell counts, but indices of immune reconstitution were similar in all groups and independent of HLA-B44.
authors.affiliation: Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth WA, Australia. pprice@cyllene.uwa.edu.au
authors.forename: P
authors.initials: P
authors.lastname: Price
authors.forename: N M
authors.initials: NM
authors.lastname: Keane
authors.forename: S F
authors.initials: SF
authors.lastname: Stone
authors.forename: K Y
authors.initials: KY
authors.lastname: Cheong
authors.forename: M A
authors.initials: MA
authors.lastname: French
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000235:genetics / Q000276:immunology*; D000328:Adult; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active; D002461:Cell Line, Transformed; D015331:Cohort Studies; D003092:Colitis / Q000235:genetics / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology; D017726:Cytomegalovirus Retinitis / Q000235:genetics / Q000276:immunology; D004334:Drug Administration Schedule; D004679:Encephalomyelitis / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics; D059948:HLA-B44 Antigen; D015795:HLA-B8 Antigen / Q000235:genetics; D006239:Haplotypes / Q000276:immunology*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D018895:Microsatellite Repeats; D015270:Mycobacterium avium-intracellulare Infection / Q000235:genetics / Q000276:immunology; D010865:Pilot Projects
chemical_list: D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D015795:HLA-B8 Antigen