Antibody testing in estimating past exposure to chlamydia trachomatis in the Netherlands chlamydia cohort study

The asymptomatic course of Chlamydia trachomatis (CT) infections can result in underestimated CT lifetime prevalence. Antibody testing might improve this estimate. We assessed CT antibody positivity and predictive factors thereof in the Netherlands Chlamydia Cohort Study. Women who had >1 CT Nucleic Acid Amplification Test (NAAT) in the study (2008–2011) and who provided self-reported information on NAATs were tested for CT major outer membrane protein specific IgG in serum (2016). CT antibody positivity was assessed and predictive factors were identified using multivariable logistic regressions, separately for CT-positive women (>1 positive NAAT or >1 self-reported positive CT test) and CT-negative women (negative by study NAAT and self

The CD14 functional gene polymorphism -260 C>T is not involved in either the susceptibility to Chlamydia trachomatis infection or the development of tubal pathology

BACKGROUND: The functional polymorphism -260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the transcriptional activity and results in a higher CD14 receptor density. Individuals carrying the T/T genotype also have significantly higher serum levels of soluble CD14. The T allele of this polymorphism has recently been linked to Chlamydia pneumoniae infection. We investigated the role of the CD14 -260 C>T polymorphism in the susceptibility to and severity (defined as subfertility and/or tubal pathology) of C. trachomatis infection in Dutch Caucasian women. METHODS: The different CD14 -260 C>T genotypes were assessed by PCR-based RFLP analysis in three cohorts: 1) A cohort (n = 576) of women attending a STD clinic, 2) a cohort (n = 253) of women with subfertility, and 3) an ethnically matched control cohort (n = 170). The following variables were used in the analysis: In cohort 1 the CT-DNA status, CT IgG serology status, self-reported symptoms and in cohort 2, the CT IgG serology status and the tubal status at laparoscopy. RESULTS: In the control cohort the CC, CT and TT genotype distribution was: 28.2%, 48.2%, and 23.5% respectively. No differences were found in the overall prevalence of CD14 -260 genotypes (28.1%, 50.7%, and 21.2%) in cohort 1 when compared to the control cohort. Also no differences were observed in women with or without CT-DNA, with or without serological CT responses, with or without symptoms, or in combinations of these three variables. In subfertile women with tubal pathology (cohort 2, n = 50) the genotype distribution was 28.0%, 48.0%, and 24.0% and in subfertile women without tubal pathology (n = 203), 27.6%, 49.3% and 23.2%. The genotype distribution was unchanged when CT IgG status was introduced in the analyses. CONCLUSION: The CD14 -260 C>T genotype distributions were identical in all three cohorts, showing that this polymorphism is not involved in the susceptibility to or severity of sequelae of C. trachomatis infection

Interruption of CXCL13-CXCR5 Axis Increases Upper Genital Tract Pathology and Activation of NKT Cells following Chlamydial Genital Infection

Peer reviewe

Specific polymorphisms in the vitamin D metabolism pathway are not associated with susceptibility to Chlamydia trachomatis infection in humans

Chlamydia trachomatis is the most common sexually transmitted bacterium worldwide. Its often asymptomatic course of infection increases chances of transmission, and increases risk of late complications. Genetic variations in the host immune system are known to impact the course of infections. Recent studies have shown a positive impact of vitamin D on the regulation of the immune system. This study assesses the impact of eight polymorphisms in five genes [VDR (rs1544410 G > A, rs2228570 C > T), CYP27B1 (rs10877012 G > T), DHCR7 (rs7944926 G > A, rs3829251 G > A), GC (rs3755967) and CYP2R1 (rs10741657 G > A, rs2060793 G > A)] on susceptibility to Chlamydia infections in humans. These polymorphisms could influence protein expression or function, and thus influence the immune system. Samples of women visiting the STD outpatient clinic in South Limburg were genotyped using the Roche Lightcycler 480. In this study, we did not observe statistically significant differences between the genotype distributions of these polymorphisms in women with or without a Chlamydia infection. This suggests that VDR, CYP27B1, DHCR7, GC and CYP2R1 do not affect the susceptibility to Chlamydia infections. However, due to its pleiotropic nature in the immune system a role for the vitamin D pathway may not be excluded from the whole clinical course of Chlamydia infections (e.g. late complications), and further research is required

Anal Lymphogranuloma Venereum Infection Screening With IgA Anti-Chlamydia trachomatis-Specific Major Outer Membrane Protein Serology

Background: Anal lymphogranuloma venereum (LGV) infections, caused by Chlamydia trachomatis biovar L (Ct+/LGV+), are endemic among men who have sex with men (MSM). Anal non-LGV biovar Ct infections (Ct+/LGV-) can be eradicated with 1 week doxycycline, whereas Ct+/LGV+ infections require 3-week doxycycline. To differentiate Ct+/LGV+ from Ct+/LGV- infections, biovar-specific Nucleic Acid Amplification Test (NAAT) are standard, but also expensive and laborious. A chlamydia-specific serological assay could serve as an alternative test. Methods: MSM were screened for anal Ct+/LGV+ and Ct+/LGV- infections with a commercial nonspecific NAAT and an in house biovar L-specific NAAT. Serum samples were evaluated with chlamydia-specific anti-Major Outer Membrane Protein (MOMP) and antilipopolysaccharide assays of IgA and IgG classes. Asymptomatic patients were identified as: (1) no anal complaints or (2) no microscopic inflammation (i.e., <10 leucocytes per high power field in anal smears). The best differentiating assay was subsequently evaluated in 100 Ct+/LGV+ and 100 Ct +/LGV- MSM using different cut-off points. Results: The anti-MOMP IgA assay was the most accurate to differentiate Ct+/LGV+ (n = 42) from Ct+/LGV+ (n = 19) with 85.7% sensitivity (95% confidence interval [CI], 72.2-93.3) and 84.2% specificity (95% CI, 62.4-94.5), even among asymptomatic patients. In a population comprising 98 Ct+/LGV+ and 105 Ct+/LGV- patients, the anti-MOMP IgA assay scored most accurate when the cut-off point was set to 2.0 with 75.5% (95% CI, 65.8-83.6) sensitivity and 74.3% (95% CI, 64.8-82.3) specificity. Conclusions: The IgA anti-MOMP assay can identify a considerable proportion of the (asymptomatic) anal LGV infections correctly. Yet, biovar L-specific NAAT are still the preferred diagnostic tests in clinical setting

TLR2, TLR4 and TLR9 genotypes and haplotypes in the susceptibility to and clinical course of Chlamydia trachomatis infections in Dutch women

Chlamydia trachomatis infections demonstrate remarkable differences in clinical course that are approximately 40% based on host genetic variation. Here, we study the single nucleotide polymorphisms (SNPs) and their haplotypes in TLR2, TLR4 and TLR9 (TLR2+2477G > A; TLR2 -16934T > A; TLR4+896A > G; TLR9-1237T > C and TLR9 +2848G > A) in relation to the susceptibility to, and severity of C. trachomatis infections. We analysed the five SNPs in a cohort of 770 Dutch Caucasian women either attending a sexually transmitted diseases outpatient clinic (n = 731) or having complaints of subfertility (n = 39). Haplotype analyses showed a trend for TLR2 haplotype I (-16934T/+2477G) to protect against the development of symptoms and tubal pathology (P-trend = 0.03) after Chlamydia infection. In the susceptibility cohort, TLR9 haplotype III (-1237C/+2848A) showed a significant decreasing trend in the development of symptoms after C. trachomatis infection (P = 0.02, OR: 0.55, 95% CI: 0.33-0.91). Logistic regression of the TLR2 haplotypes, TLR4+896A > G, and TLR9 haplotypes showed that the TLR2 haplotype combinations AG-TA and AG-TG confer risk (OR 3.4 (P = 0.01) and 1.6 (P = 0.03)), while the TLR9 haplotype combination TG-TA protects against C. trachomatis infections (OR: 0.4, P = 0.004). Our study shows that both TLR2 and TLR9 genes and SNP combinations do influence the clinical course of Chlamydia infections

Antibody Testing in Estimating Past Exposure to Chlamydia trachomatis in The Netherlands Chlamydia Cohort Study

The asymptomatic course of Chlamydia trachomatis (CT) infections can result in underestimated CT lifetime prevalence. Antibody testing might improve this estimate. We assessed CT antibody positivity and predictive factors thereof in the Netherlands Chlamydia Cohort Study. Women who had ≥1 CT Nucleic Acid Amplification Test (NAAT) in the study (2008-2011) and who provided self-reported information on NAATs were tested for CT major outer membrane protein specific IgG in serum (2016). CT antibody positivity was assessed and predictive factors were identified using multivariable logistic regressions, separately for CT-positive women (≥1 positive NAAT or ≥1 self-reported positive CT test) and CT-negative women (negative by study NAAT and self-report). Of the 3,613 women studied, 833 (23.1%) were CT -positive. Among the CT-negative women, 208 (7.5%, 95%CI 6.5-8.5) tested positive for CT antibodies. This increased CT lifetime prevalence with 5.8% (95%CI 5.0-6.5). Among women with a CT-positive history, 338 (40.6%, 95%CI 38.5-44.1) tested positive. Predictive factors for antibody positivity related to lower social economic status, sexual risk behavior, multiple infections, higher body mass index, and non-smoking. CT antibody testing significantly increased the lifetime prevalence. Combining NAAT outcomes, self-reported positive tests, and antibody testing reduced misclassification in CT prevalence estimates

Antibody Testing in Estimating Past Exposure to C in the Netherlands Chlamydia Cohort Study.

The asymptomatic course of Chlamydia trachomatis (CT) infections can result in underestimated CT lifetime prevalence. Antibody testing might improve this estimate. We assessed CT antibody positivity and predictive factors thereof in the Netherlands Chlamydia Cohort Study. Women who had ≥1 CT Nucleic Acid Amplification Test (NAAT) in the study (2008-2011) and who provided self-reported information on NAATs were tested for CT major outer membrane protein specific IgG in serum (2016). CT antibody positivity was assessed and predictive factors were identified using multivariable logistic regressions, separately for CT-positive women (≥1 positive NAAT or ≥1 self-reported positive CT test) and CT-negative women (negative by study NAAT and self-report). Of the 3,613 women studied, 833 (23.1%) were CT -positive. Among the CT-negative women, 208 (7.5%, 95%CI 6.5-8.5) tested positive for CT antibodies. This increased CT lifetime prevalence with 5.8% (95%CI 5.0-6.5). Among women with a CT-positive history, 338 (40.6%, 95%CI 38.5-44.1) tested positive. Predictive factors for antibody positivity related to lower social economic status, sexual risk behavior, multiple infections, higher body mass index, and non-smoking. CT antibody testing significantly increased the lifetime prevalence. Combining NAAT outcomes, self-reported positive tests, and antibody testing reduced misclassification in CT prevalence estimates

Antibody testing in estimating past exposure to chlamydia trachomatis in the Netherlands chlamydia cohort study

The asymptomatic course of Chlamydia trachomatis (CT) infections can result in underestimated CT lifetime prevalence. Antibody testing might improve this estimate. We assessed CT antibody positivity and predictive factors thereof in the Netherlands Chlamydia Cohort Study. Women who had >1 CT Nucleic Acid Amplification Test (NAAT) in the study (2008–2011) and who provided self-reported information on NAATs were tested for CT major outer membrane protein specific IgG in serum (2016). CT antibody positivity was assessed and predictive factors were identified using multivariable logistic regressions, separately for CT-positive women (>1 positive NAAT or >1 self-reported positive CT test) and CT-negative women (negative by study NAAT and self-report). Of the 3,613 women studied, 833 (23.1%) were CT-positive. Among the CT-negative women, 208 (7.5%, 95% CI 6.5–8.5) tested positive for CT antibodies. This increased CT lifetime prevalence with 5.8% (95% CI 5.0–6.5). Among women with a CT-positive history, 338 (40.6%, 95% CI 38.5–44.1) tested positive. Predictive factors for antibody positivity related to lower social economic status, sexual risk behavior, multiple infections, higher body mass index, and non-smoking. CT antibody testing significantly increased the lifetime prevalence. Combining NAAT outcomes, self-reported positive tests, and antibody testing reduced misclassification in CT prevalence estimates