HLA ANTIGEN AND ANTIBODY RESPONSE TO C TRACHOMATIS--RISK FOR C SALPINGITIS

HLA 抗原和抗体对沙眼衣原体的反应——衣原体输卵管炎的风险

• 批准号: 5205617
• 负责人: ROBERT C BRUNHAM
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5205617
• 关键词: Chlamydia trachomatis; HIV infections; alleles; antibacterial antibody; antigen antibody reaction; cervix disorder; chlamydial disease; disease /disorder proneness /risk; enzyme linked immunosorbent assay; female; helper T lymphocyte; histocompatibility antigens; histocompatibility typing; host organism interaction; human subject; immunopathology; longitudinal human study; salpingitis; serology /serodiagnosis; sexually transmitted diseases; stress proteins

Sexually transmitted Chlamydia trachomatis infection is extremely common and commonly produces salpingitis in infected women. Seroepidemiologic data suggest that post-salpingitis sequela of C.trachomatis infection such as tubal infertility or ectopic pregnancy are accompanied by immune responses to the chlamydial heat shock protein 60 (hsp60) antigen. Animal experiments suggest that chlamydial disease is attributable to immunopathologic responses to the chlamydial hsp60 antigen. Immune responses to hsp60 are genetically determined and in the mouse linked in part to the H-2 locus. Based on these observations, the hypothesis of the present proposal is that HLA genes, by determining antibody responses to the chlamydial hsp60 in humans, are a risk factor for clinical salpingitis following chlamydial cervical infection. HIV infection is speculated to interrupt this pathogenetic pathway by reducing immune responses to hsp60. To address this hypothesis, 300 women (approximately 200 HIV infected and 100 HIV uninfected) who are commercial sex workers in the Pumwani district of Nairobi, Kenya will be followed for up to four years for incident infections with c.trachomatis and for the occurrence of clinical salpingitis. All women will be HLA typed (class I by standard serologic tests and class II by DR, DP and DQ oligotyping) and have baseline serologic evaluation for antibodies to chlamydial hsp60. Cloned recombinant chlamydial hsp60 and synthetic peptides will be used in a variety of serologic formats. The sample size is sufficient to detect a increased relative risk of greater than or equal to 1.86 if hsp60 antibodies are correlated with a specific HLA allele and to detect an increased relative risk of greater than or equal to 1.68 if acute salpingitis is associated with an antibody response to the chlamydial hsp60. This study should define the molecular and genetic basis for chlamydial salpingitis and may help define new approaches to improved treatment or prevention of this disease.

性传播沙眼衣原体感染极为常见 受感染的女性通常会产生输卵管炎。 血清流行病学 数据提示沙眼衣原体感染后输卵管炎后遗症 如输卵管性不孕或宫外孕都伴有免疫 对衣原体热休克蛋白 60 (hsp60) 抗原的反应。 动物实验表明衣原体病可归因于 对衣原体 hsp60 抗原的免疫病理反应。 免疫 对 hsp60 的反应是由基因决定的，并且在小鼠中与 H-2 基因座的一部分。 基于这些观察，本提案的假设是 通过确定对衣原体 hsp60 的抗体反应来识别 HLA 基因 在人类中，是以下临床输卵管炎的危险因素 宫颈衣原体感染。 据推测，艾滋病毒感染会中断 这种致病途径是通过减少对 hsp60 的免疫反应来实现的。 到 为了验证这一假设，研究人员对 300 名女性（约 200 名 HIV 感染者和 100 名未感染 HIV 的人）是 Pumwani 地区的商业性工作者 肯尼亚内罗毕地区将被跟踪长达四年 沙眼衣原体感染事件和临床症状的发生 输卵管炎。 所有女性都将进行 HLA 分型（标准血清学 I 类） 测试和 II 类（通过 DR、DP 和 DQ 寡分型）并具有基线 衣原体 hsp60 抗体的血清学评估。 克隆 重组衣原体 hsp60 和合成肽将用于 多种血清学形式。 样本量足以检测 如果 hsp60 则相对风险增加大于或等于 1.86 抗体与特定的 HLA 等位基因相关并检测 如果是急性的，相对风险增加大于或等于 1.68 输卵管炎与衣原体抗体反应有关 热休克蛋白60。 这项研究应明确衣原体的分子和遗传基础 输卵管炎，可能有助于确定改善治疗的新方法或 预防这种疾病。