Dataset Information

Genome-wide identification of Chlamydia trachomatis antigens associated with trachomatous trichiasis.

ABSTRACT:

Purpose

Chlamydia trachomatis is the leading infectious cause of blindness. The goal of the current study was to search for biomarkers associated with C. trachomatis-induced ocular pathologies.

Methods

We used a whole genome scale proteome array to systematically profile antigen specificities of antibody responses to C. trachomatis infection in individuals from trachoma-endemic communities with or without end-stage trachoma (trichiasis) in The Gambia.

Results

When 61 trichiasis patients were compared with their control counterparts for overall antibody reactivity with organisms of different chlamydial species, no statistically significant difference was found. Both groups developed significantly higher titers of antibodies against C. trachomatis ocular serovars A and B than ocular serovar C, genital serovar D, or Chlamydia psittaci, whereas the titers of anti-Chlamydia pneumoniae antibodies were the highest. When antisera from 33 trichiasis and 26 control patients (with relatively high titers of antibodies to C. trachomatis ocular serovars) were reacted with 908 C. trachomatis proteins, 447 antigens were recognized by at least 1 of the 59 antisera, and 10 antigens by 50% or more antisera, the latter being designated as immunodominant antigens. More importantly, four antigens were preferentially recognized by the trichiasis group, with antigens CT414, CT667, and CT706 collectively reacting with 30% of trichiasis antisera but none from the normal group, and antigen CT695 reacting with 61% of trichiasis but only 31% of normal antisera. On the other hand, eight antigens were preferentially recognized by the control group, with antigens CT019, CT117, CT301, CT553, CT556, CT571, and CT709 together reacting with 46% of normal antisera and none from the trichiasis group, whereas antigen CT442 reacted with 35% of normal and 19% of trichiasis antisera respectively.

Conclusions

The current study, by mapping immunodominant C. trachomatis antigens and identifying antigens associated with both ocular pathology and protection, has provided important information for further understanding chlamydial pathogenesis and the development of subunit vaccines.

SUBMITTER: Lu C

PROVIDER: S-EPMC3366722 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Publications

Genome-wide identification of Chlamydia trachomatis antigens associated with trachomatous trichiasis.

Lu Chunxue C Holland Martin J MJ Gong Siqi S Peng Bo B Bailey Robin L RL Mabey David W DW Wu Yimou Y Zhong Guangming G

Investigative ophthalmology & visual science 20120514 6

<h4>Purpose</h4>Chlamydia trachomatis is the leading infectious cause of blindness. The goal of the current study was to search for biomarkers associated with C. trachomatis-induced ocular pathologies.<h4>Methods</h4>We used a whole genome scale proteome array to systematically profile antigen specificities of antibody responses to C. trachomatis infection in individuals from trachoma-endemic communities with or without end-stage trachoma (trichiasis) in The Gambia.<h4>Results</h4>When 61 trichi ...[more]

PMID: 22427578

Similar Datasets

Project description:PurposeUnfavorable outcomes after trachomatous trichiasis (TT) surgery are undermining the global trachoma elimination effort. This analysis investigates predictors of postoperative TT (PTT), eyelid contour abnormalities (ECAs), and granuloma in the 2 most common TT surgery procedures: posterior lamellar tarsal rotation (PLTR) and bilamellar tarsal rotation (BLTR).DesignSecondary data analysis from a randomized, controlled, single-masked clinical trial.ParticipantsA total of 1000 patients with TT, with lashes touching the eye or evidence of epilation, in association with tarsal conjunctival scarring.MethodsParticipants were randomly allocated and received BLTR (n = 501) or PLTR (n = 499) surgery. Disease severity at baseline, surgical incisions, sutures, and corrections were graded during and immediately after surgery. Participants were examined at 6 and 12 months by assessors masked to allocation.Main outcome measuresPredictors of PTT, ECA, and granuloma.ResultsData were available for 992 (99.2%) trial participants (496 in each arm). There was strong evidence that performing more peripheral dissection with scissors in PLTR (odd ratio [OR], 0.70; 95% confidence interval [CI], 0.54-0.91; P = 0.008) and BLTR (OR, 0.83; 95% CI, 0.72-0.96; P = 0.01) independently protected against PTT. Baseline major trichiasis and mixed location lashes and immediate postoperative central undercorrection independently predicted PTT in both surgical procedures. Peripheral lashes in PLTR (OR, 5.91; 95% CI, 1.48-23.5; P = 0.01) and external central incision height ≥4 mm in BLTR (OR, 2.89; 95% CI, 1.55-5.41; P = 0.001) were independently associated with PTT. Suture interval asymmetry of >2 mm (OR, 3.18; 95% CI, 1.31-7.70; P = 0.01) in PLTR and baseline conjunctival scarring in BLTR (OR, 1.72; 95% CI, 1.06-2.81; P = 0.03) were independently associated with ECA. Older age was independently associated with ECA in both PLTR (P value for trend < 0.0001) and BLTR (P value for trend = 0.03). There was substantial intersurgeon variability in ECA rates for both PLTR (range, 19.0%-36.2%) and BLTR (range, 6.1%-28.7%) procedures. In PLTR surgery, irregular posterior lamellar incision at the center of the eyelid (OR, 6.72; 95% CI, 1.55-29.04; P = 0.01) and ECA (OR, 3.08; 95% CI, 1.37-6.94; P = 0.007) resulted in granuloma formation.ConclusionsPoor postoperative outcomes in TT surgery were associated with inadequate peripheral dissection, irregular incision, asymmetric suture position and tension, inadequate correction, and lash location. Addressing these will improve TT surgical outcomes.

Project description:BackgroundTrachoma is the leading preventable cause of global blindness. A balanced Th1/Th2/Th3 immune response is critical for resolving Chlamydia trachomatis infection, the primary cause of trachoma. Despite control programs that include mass antibiotic treatment, reinfection and recurrence of trachoma are common after treatment cessation. Furthermore, a subset of infected individuals develop inflammation and are at greater risk for developing the severe sequela of trachoma known as trachomatous trichiasis (TT). While there are a number of environmental and behavioral risk factors for trachoma, genetic factors that influence inflammation and TT risk remain ill defined.Methodology/findingsWe identified single nucleotide polymorphisms (SNP) in 36 candidate inflammatory genes and interactions among these SNPs that likely play a role in the overall risk for TT. We conducted a case control study of 538 individuals of Tharu ethnicity residing in an endemic region of Nepal. Trachoma was graded according to World Health Organization guidelines. A linear array was used to genotype 51 biallelic SNPs in the 36 genes. Analyses were performed using logic regression modeling, which controls for multiple comparisons. We present, to our knowledge, the first significant association of TNFA (-308GA), LTA (252A), VCAM1 (-1594TC), and IL9 (T113M) polymorphisms, synergistic SNPs and risk of TT. TT risk decreased 5 times [odds ratio = 0.2 (95% confidence interval 0.11.-0.33), p = 0.001] with the combination of TNFA (-308A), LTA (252A), VCAM1 (-1594C), SCYA 11 (23T) minor allele, and the combination of TNFA (-308A), IL9 (113M), IL1B (5'UTR-T), and VCAM1 (-1594C). However, TT risk increased 13.5 times [odds ratio = 13.5 (95% confidence interval 3.3-22), p = 0.001] with the combination of TNFA (-308G), VDR (intron G), IL4R (50V), and ICAM1 (56M) minor allele.ConclusionsEvaluating genetic risk factors for trachoma will advance our understanding of disease pathogenesis, and should be considered in the context of designing global control programs.

Project description:Importance: Trichiasis surgery programs globally have faced high rates of poor surgical outcomes. Identifying correctable risk factors for improving long-term outcomes is essential for countries targeting elimination of trachoma as a public health problem.Objective: To determine whether the location of trichiatic eyelashes prior to surgery influences development of post-operative trichiasis (PTT) within two years after surgery.Design: Secondary data analysis of four randomized clinical trials evaluating methods to improve trichiasis surgery outcomes. These include the Surgery for Trichiasis, Antibiotics for Recurrence (STAR) trial, Partnership for Rapid Elimination of Trachoma (PRET-Surgery), absorbable versus silk sutures trial, and epilation versus surgery for minor trichiasis trial.Setting: Primary trials were conducted in rural areas of Ethiopia and Tanzania.Interventions or exposures: Trichiasis surgery performed with either the bilamellar tarsal rotation procedure or posterior lamellar rotation procedure.Main outcomes: Prevalence of PTT within two years after surgery, location of trichiatic eyelashes pre-operatively and post-operatively.Results: 6,747 eyelids that underwent first-time trichiasis surgery were included. PTT rates varied by study, ranging from 10-40%. PTT was less severe (based on number of trichiatic eyelashes) than initial trichiasis for 72% of those developing PTT, and only 2% of eyelids were worse at follow up than pre-operatively. Eyelids with central only-trichiasis pre-operatively had lower rates of PTT than eyelids with peripheral only trichiasis in each of the three trials that included severe TT cases. 10% of eyelids with peripheral trichiasis pre-operatively that develop PTT have central TT post-operatively.Conclusions and relevance: Pre-operative central trichiasis is less likely than peripheral trichiasis to be associated with subsequent PTT. Regardless of type of surgery, surgeon skill levels, or pre-operative trichiasis severity, the presence of peripheral trichiasis pre-operatively is associated with higher rates of PTT. Making an incision that extends the length of the eyelid and adequately rotating the nasal and temporal aspects of the eyelid when suturing may help to minimize the chance of developing peripheral PTT.Trial registration: ClinicalTrials.gov PRET: NCT00886015; Suture: NCT005228560; Epilation: NCT00522912.

Project description:PurposeEight million people have trachomatous trichiasis (TT). The World Health Organization (WHO) recommends entropion surgery for TT regardless of severity. However, epilation is widely practiced for treating minor TT (1-5 lashes touching the globe). We report the frequency and effectiveness of patient-initiated epilation and its relationship to corneal opacity.DesignCross-sectional baseline data of individuals recruited to 2 randomized, clinical trials.ParticipantsWe included 2556 individuals (4310 eyes) with previously unoperated TT in ≥ 1 eye.MethodsA single ophthalmologist examined all participants for signs of trachoma using WHO grading systems with additional assessment of entropion grading, location and number of trichiatic lashes, and evidence of epilation. A questionnaire enquired about epilation practices.Main outcome measuresThe association between epilation and degree of corneal opacity. Epilation practices of TT patients.ResultsCentral corneal scarring was present in 1436 (33%) eyes. Entropion was absent/mild in 2328 (54%) eyes, moderate in 1259 (29.2%), and severe in 723 (16.8%). The median number of lashes touching the eye was 2 (interquartile range, 1-5; range, 0-133). There was clinical evidence of epilation in 3018 (70%) eyes, of which 738 (24%) were successfully epilated (no lashes touching globe). Epilation was performed frequently (at least monthly in 3311 [76.8%] eyes), by someone other than the patient (92.8%), and using locally made forceps (88.9%). Controlling for age and degree of entropion, successful epilation was associated with less corneal opacity (odds ratio [OR], 0.61; 95% confidence interval [CI]. 0.43-0.88; P = 0.007). The association was only significant in patients with severe entropion (OR, 0.07; 95% CI, 0.02-0.25; P<0.005).ConclusionsWe found an association between successful epilation and less central corneal opacity. This indicates the importance of preventing eyelashes from touching the cornea, particularly in individuals with severe entropion. This is a cross-sectional study; therefore, a causative relationship cannot be concluded. However, the results suggest that among patients who decline or are unable to access surgery, and perhaps in minor TT where the management remains controversial, the provision of high-quality forceps and epilation training may be beneficial.Financial disclosure(s)The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Dataset Information

Genome-wide identification of Chlamydia trachomatis antigens associated with trachomatous trichiasis.

Purpose

Methods

Results

Conclusions

Publications

Genome-wide identification of Chlamydia trachomatis antigens associated with trachomatous trichiasis.

Similar Datasets

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