Human Leukocyte Antigen and Cytokine Gene Variants as Predictors of Recurrent<i>Chlamydia trachomatis</i>Infection in High‐Risk Adolescents

Abstract

Antigen presentation and immune activation are essential to the effective control of infectious diseases. In 485 North American adolescents at high risk for genital Chlamydia trachomatis infection, we found 2 human leukocyte antigen variants (DRB1*03-DQB1*04 and DQB1*06) to be associated with recurrent Chlamydia infection (adjusted relative odds [RO], 12.0; , for both variants). A G-C-C haplotype corresponding to P ! .01 variants at IL10 (encoding interleukin-10 [IL-10]) promoter positions 1082, 819, and 592 was underrepresented in individuals with recurrent infection (RO, 0.59; ). These genetic associations were P p .046 independent of nongenetic factors, including number of sex partners, race, sex, duration of follow-up, and human immunodeficiency virus type 1 seropositivity. Consistent with the observed IL10 association, cervical secretions in female adolescents without the IL10 G-C-C haplotype had elevated IL-10 concentrations after Chlamydia infection, which may reflect involvement of a Chlamydia-specific mechanism for genetically mediated, differential IL-10 expression in the genital tract. Sexually transmitted Chlamydia trachomatis infection is diagnosed in 3 million people each year in the United States alone [1, 2]. Those with the highest prevalence of Chlamydia infection are 15-24-year-old adolescents and youth, who represent 25% of the sexually experienced population [2]. Spontaneous clearance of C. trachomatis from the lower genital tract in nearly 20% of Chlamydia infections clearly suggests that the host immune response often controls this infection before