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5th International AIDS Society Conference on HIV Pathogenesis and TreatmentCape Town - July 19 - 22, 2009 |
NEW ASSOCIATIONS REPORTED BETWEEN HLA ALLELES AND THE DEVELOPMENT OF MILIARY TUBERCULOUS AND TUBERCULOUS GASTROINTESTINAL DISEASE
IAS Conf HIV Pathog Treat 2009 Jul 19-22;5th: Abstract No. MOPDA105
W. Shandera1,2, A. Karstaedt3,4, G. Land5,6
1Baylor College of Medicine, Internal Medicine, Houston, Texas, United States, 2Ben Taub General Hospital, Internal Medicine, Houston, Texas, United States, 3University of the Witwatersrand, Internal Medicine, Johannesburg, South Africa, 4Chris Hani Baragwanath Hospital, Internal Medicine, Soweto, Johannesburg, South Africa, 5Methodist Hospital, HLA and Transplant Immunology, Houston, Texas, United States, 6Weill Cornell Medical College, Clinical Pathology, Houston, Texas, United States
BACKGROUND: Human leukocyte antigen (HLA) associations with extrapulmonary tuberculosis (EPTB) in the setting of HIV infection and AIDS are unknown.
METHODS: Patients presenting over four years with EPTB were interviewed with respect to their length/site of illness, HIV status, and demographics. Blood samples were analyzed for the major histocompatibility antigens (HLA-A, HLA-B, HLADR, HLA-DQ). Results were analyzed by STATA (6.0).
RESULTS: 41 patients with EPTB were identified and provided samples for HLA testing. The mean age on presentation was 41, the M:F ratio 2.33: 1. The cohorts included 20 from the USA (10 Hispanics, 8 African-Americans, 1 Caucasian, 1 Asian (Pakistani) and 21 from South Africa (all black South African). HIV seropositivity was documented in 50% of the US cohort and an estimated 76% overall. Two HLA associations were made. First, among seven patients with miliary (disseminated) tuberculous, all were either homozygous for the HLA-DQ1 allele or showed the presence of a HLA-DQB1*03XX allele (7 of 7 with miliary tuberculosis fulfilled the criteria vs 9 of 24 without miliary tuberculous, P=0.004, Fisher's exact test. Bonferroni correction, P=0.032). Among four patients with gastrointestinal tuberculosis, all showed either homozygosity for the HLA-A allele (1) or presence of the HLA- A33 allele (3) (4 of 4 with gastrointestinal disease fulfilled the criteria vs 8 of 37 without gastrointestinal disease, P=0.005, Fisher's exact test, Bonferroni correction, P=0.04). Both associations persisted in a multivariate analysis that included black race, study site, and HIV status.
CONCLUSIONS: Homozygosity at the DQ allele and/or presence of the DQB1*03XX allele are associated with miliary tuberculous while homozygosity at the HLA-A allele and/or the presence of the HLA-A33 allele are associated with tuberculous gastrointestinal disease. The DQB1*03XX allele may represent a binding site described in the past by serological techniques as DQ1.
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2009-07-22
MOPDA105
Poster Discussion MOPDA1 - HLA Pathogen Interactions
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