Anti‐chlamydia IgG and IgA are insufficient to prevent endometrial chlamydia infection in women, and increased anti‐chlamydia IgG is associated with enhanced risk for incident infection

Abstract

Problem Chlamydia infections in women can ascend to the upper genital tract, and repeated infections are common, placing women at risk for sequelae. The protective role of anti‐chlamydia antibodies to surface exposed antigens in ascending and incident infection is unclear. Method of study A whole‐bacterial ELISA was used to quantify chlamydia‐specific IgG and IgA in serum and cervical secretions of 151 high‐risk women followed longitudinally. Correlations were determined between antibody and cervical burden, and causal mediation analysis investigated the effect of antibody on ascension. We examined the relationship of antibody to incident infection using the marginal Cox model. Results Serum and cervical anti‐chlamydia IgG and cervical IgA levels correlated inversely with cervical burden. While lower burden was associated with reduced ascension, causal mediation analysis revealed that the indirect effects of antibody mediated through reductions in bacterial burden were insufficient to prevent ascension. Analysis of women uninfected at enrollment revealed that serum and cervical anti‐chlamydia IgG were associated with increased risk of incident infection; hazard ratio increased 3.6‐fold (95% CI, 1.3‐10.3), and 22.6‐fold (95% CI, 3.1‐165.2) with each unit of serum and cervical IgG, respectively. Conclusion Although anti‐chlamydia IgG and IgA correlated with reduced cervical chlamydia burden, they failed to prevent ascension and increased levels of anti‐chlamydia IgG were associated with increased risk for incident infection.

Chlamydia Prevalence by Age and Correlates of Infection Among Pregnant Women

“…1 Whether this is due to anatomy (cervical ectropion that resolves with age), immunology (acquired immunity to chlamydia with age), or behavioral patterns (more sex partners or higher risk sex partners in younger women) remains unclear. 22 In HIV-discordant couples, pregnancy is associated with 2-fold increased risk of HIV acquisition compared with nonpregnant women (7.4 vs. 3.0 incident infections per 100 person-years). 23 Other independent predictors of chlamydia infection in pregnancy in our study included Black race.…”

Antibodies to Variable Domain 4 Linear Epitopes of theChlamydia trachomatisMajor Outer Membrane Protein Are Not Associated with Chlamydia Resolution or Reinfection in Women

“…To date, the only identified correlate of protection against C. trachomatis infection in humans is IFN-γ-producing CD4 + T cells, which have been shown to be associated with decreased frequency of C. trachomatis incidence and reinfection ( 9 – 11 ). Anti- C. trachomatis IgG and IgA are inversely correlated with cervical C. trachomatis burden, suggesting that antibodies may control C. trachomatis at the initial site of infection, but these antibodies are insufficient to prevent the ascension of C. trachomatis into the upper genital tract in women ( 12 ). In addition, women are commonly reinfected with the same C. trachomatis serovar, suggesting that serovar-specific anti-MOMP antibodies elicited during urogenital infection do not provide complete protective immunity ( 13 ).…”

“…Animal models of C. trachomatis infection suggest that antibodies may play a role in protection from C. trachomatis reinfection, but are not required for C. trachomatis clearance. Animal models show that antibodies to particular antigens and epitopes may provide protection (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Rabbit IgG specific for serovar L2 major outer membrane protein (MOMP) (6), and some MOMP monoclonal antibodies have in vitro neutralizing activity.…”

Shift work influences the outcomes of Chlamydia infection and pathogenesis

“…The results showed that infected control mice had higher IgG and lower IgG 2C than infected ECD mice in the third and fourth week of infection. The role of antibodies in the immune response against Chlamydia is not fully understood with arguments being made that antibodies are not important in Chlamydia clearance 53 – 57 . In infected control mice IgG is predominant, while in infected ECD mice IgG 2C is predominant, this could be associated with the high load of Chlamydia in ECD mice, compared to infected control mice.…”