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.


METHODS
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 and 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 and showed no distinct patterns.


CONCLUSIONS
Distinct cytokine-mediated mechanisms contribute to IRD initiated by herpesvirus and mycobacterial infections.
Price
Patricia
P
Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Australia.
Morahan
Grant
G
Huang
Dexing
D
Stone
Emma
E
Cheong
Karey Y M
KY
Castley
Alison
A
Rodgers
Marina
M
McIntyre
Meredith Q
MQ
Abraham
Lawrence J
LJ
French
Martyn A
MA
D017088:AIDS-Related Opportunistic Infections / Q000235:genetics* / Q000276:immunology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016207:Cytokines / Q000235:genetics*; D017726:Cytomegalovirus Retinitis / Q000235:genetics* / Q000276:immunology; D004679:Encephalomyelitis / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000150:complications; D015497:HIV-1; D006801:Humans; D007107:Immune System; D015270:Mycobacterium avium-intracellulare Infection / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic
D016207:Cytokines