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ASSOCIATION OF HLA GENOTYPES WITH THE OCCURRENCE OF AND CYTOKINE RESPONSES TO TWO COMMON SEXUALLY TRANSMITTED INFECTIONS IN ADOLESCENTS.
Chengbin Wang MSPH 1, Jianming Tang PhD 2, William M. Geisler MD 2, Craig M. Wilson MD 3 and Richard A. Kaslow MD 1. 1 Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA ; 2 Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA and 3 Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA .
For a cohort of 485 adolescents (mean age = 17 yrs) at high risk of HIV-1 infection and other sexually transmitted infections (STIs), molecular genotyping was performed for HLA and cytokine genes including HLA-A, -B, -C, -DRB1, DQB1, IL2, IL4, IL6, IL10, IL12B, and TNF. Association analyses using multivariable logistic regression models revealed that several HLA variants (e.g., DQB1*06, B*44-Cw*04, and B*53-Cw*04) are independently associated with genital Chlamydia and Gonorrhea infections (adjusted odds ratios = 1.8-3.2, P < 0.05 for all). In the subset of female adolescents (n = 396) with endocervical cytokines measured by ELISA at 6-month intervals, both bacterial STIs are characterized by elevated interleukin-10 (IL-10) and IL-12, accompanied by reduced IL-2 after incident infection. Differences in cytokine response to Chlamydia and Gonorrhea infection were more readily associated with HLA gene than cytokine gene variants. For example, IL-12 increased by 3-fold in DQB1*06 negative subjects compared with positives (P = 0.01), while IL-2 decreased in the B*44-Cw*04 negative subjects and slightly increased in positive subjects (P = 0.02). In each case, the baseline cytokine levels also differed between patient groups defined by the presence and absence of a given HLA variant, suggesting that HLA-associated variability in immune responses can be extended from antigen presentation to the production of immunoregulatory cytokines.