The Complexity of HLA Class II (DRB1, DQB1, DM) Associations With Disseminated Mycobacterium Avium Complex Infection Among HIV-1–Seropositive Whites

Abstract

Earlier associations of polymorphism in classic HLA class II (DRB1 and DQB1) genes have been extended to include the accessory genes DMA and DMB as determinants of disseminated Mycobacterium avium complex (DMAC) infection among HIV-1-seropositive whites. From the Multicenter AIDS Cohort study, 176 DMAC cases were matched with 176 controls in a nested case-control study. PCR-based HLA genotyping techniques were used to resolve variants of DRB1 and DQB1 to their four-digit or five-digit alleles, and single-strand conformation polymorphism was used to resolve sequences in exon 3 at each DM locus. The DMA*0102 allele occurred less frequently among DMAC cases than among controls (OR = 0.46, p =.02). Combinations of DRB1 alleles with or without specific DMA and DMB variants showed significant differences in distributions between the cases and controls, but both of the previously associated class II alleles (DRB1*1501 and DRB1*0701) showed stronger positive associations with DMAC in the absence than in the presence of DMA*0102. Apparent joint effects of DRB1 and DM allelic combinations on occurrence and timing of DMAC suggest that class II disease relationships may be better predicted by biologically plausible interactive combinations than by polymorphisms in individual genes.

Susceptibility to nontuberculous mycobacterial lung disease

“…HLA genotyping of HIV-positive patients with disseminated MAC has revealed positive associations with the DR2, DQB1*0601 and DRB1*0701 alleles, and a negative association with the DMA*0102 allele [98]. Two Japanese groups have identified HLA antigens including DR6, DQ4, A33 and A26 as being more common among patients with MACLD without pre-existing lung disease [56,57]; A26 was associated with progression of disease.…”

Impact of host genetics on HIV disease progression and treatment

“…In the case of the common Caucasian MHC haplotype that includes HLA-A1/ -B8/-DR3 alleles, these data indicate that individuals carrying this haplotype experience more rapid CD4 Tcell decline and are generally at increased risk of opportunistic infections; but at the same remain at low risk of developing Kaposi's sarcoma [50,51]. Susceptibility to disseminated Mycobacterium avium complex infection has also been linked to Class II MHC region, in this case to the closely linked HLA-DRB1 Ã 1501 and -DQ Ã 0602 alleles previously associated with risk of tuberculosis and leprosy in populations where these diseases are prevalent [53,54]. Immune restoration disease (IRD) associated with aberrant inflammatory responses to pathogens following the introduction of antiretroviral therapy have also been associated with HLA alleles, with significant associations noted between the HLA-B44/-DR4 MHC haplotype and cytomegalovirus-related IRD [55].…”

Proctitis Caused by Mycobacterium avium-intracellulare in an HIV-Infected Patient

“…There may be a genetic predisposition for acquiring this infection. In a case-control study from the Multicenter AIDS Cohort, specific human leukocyte antigen (HLA) class II alleles (DRB1, DQB, DM) were more commonly associated with MAI disease [ 7 ]. An innate susceptibility could explain the development of MAI infection in our patient.…”