Mycobacterium tuberculosis/HIV-1 coinfection and disease: role of human leukocyte antigen variation.
Genetic variation influences immune responses and may contribute to differential development of tuberculosis (TB), particularly in immunosuppressed individuals. To examine the risk of Mycobacterium tuberculosis infection progressing to disease in the context of M. tuberculosis/human immunodeficiency virus (HIV) type 1 coinfection, HIV-1 RNA load and human leukocyte antigen (HLA) genotypes were determined among subjects from Harare, Zimbabwe, an area where both TB and HIV-1 are endemic. Patients with TB were compared with control subjects, stratified by HIV-1 infection status and progression of TB disease. Alleles of class I HLA-A and -C were associated with risk of developing active TB, depending on HIV-1 status. Among HIV-positive subjects, HIV-1 load was independently associated with increased risk of developing pulmonary TB. HLA DRB1 homozygosity among HIV-positive subjects was associated with reduced risk of developing pulmonary TB but increased risk of rapid progression to pleural effusion TB. These observations suggest that HLA plays a role in risk of developing symptomatic TB at various stages of disease and that these effects are modified by HIV-1 coinfection.
Louie
Leslie G
LG
Research Department, Children's Hospital and Research Center at Oakland, California 94609-1673, USA. llouie@chori.org
Hartogensis
Wendy E
WE
Jackman
Rachael P
RP
Schultz
Kathleen A
KA
Zijenah
Lynn S
LS
Yiu
Carina H-Y
CH
Nguyen
Viet D
VD
Sohsman
Marie Y
MY
Katzenstein
David K
DK
Mason
Peter R
PR
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000235:genetics / Q000276:immunology*; D000328:Adult; D000483:Alleles; D005260:Female; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015497:HIV-1; D015234:HLA-A Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D014376:Tuberculosis / Q000150:complications / Q000235:genetics / Q000276:immunology*
D015234:HLA-A Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains