ANTIGEN D8/17 AS A MARKER FOR CHILDHOOD ONSET OCD/TS

抗原 D8/17 作为儿童期发作 OCD/TS 的标志物

• 批准号: 2035248
• 负责人: Wayne K Goodman
• 金额: $ 28.67万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2035248
• 关键词: B lymphocyte; CD antigens; Streptococcus infection; Tourette's syndrome; adolescence (12-20); adult human (21+); biomarker; child (0-11); chorea minor; clinical research; developmental immunology; disease /disorder etiology; disease /disorder proneness /risk; fluorescence microscopy; human subject; immunofluorescence technique; longitudinal human study; mental disorder diagnosis; monoclonal antibody; obsessive compulsive disorder; rheumatic fever; statistics /biometry

DESCRIPTION (Adapted from applicant's abstract): An autoimmune response to streptococcal antigens is believed to produce rheumatic fever (RF), including one of its major manifestations, Sydenham's chorea (SC). An interplay of genetic, developmental, and environmental factors determines vulnerability to these complications of strep infection. Swedo et al, have hypothesized that SC may be a medical model for some forms of tic and obsessive compulsive disorders (OCD). We sought a marker that could identify which and how many cases of OCD or Tourette's Syndrome (TS) might have an illness that bears a pathobiologic relationship of SC. Monoclonal antibody (mAb) D8/17 identifies a B cell antigen with expanded expression in all patients with RF, 15percent of unaffected relatives of patients with RF, and in about 5 of controls. It is thought to be a trait marker for susceptibility to RF. In our pilot study, 31 clinic patients ages 7-24 years with childhood-onset OCD and/or TS participated. None carried the diagnosis of RF or SC. D8/17 was positive in all patients whereas only 1 of 21 healthy control was positive. These findings suggest that D8/17 may serve as a marker for shared susceptibility amongst childhood-onset OCD, TS, and SC. The proposed study will address the following questions: 1) Is D8/17 positivity specific to childhood-onset OCD/TS? The frequency of D8/17 positivity in a cohort of 45 patients with childhood onset OCD/TS will be compared with 30 patients with adult onset OCD and 30 ages/sex-matched healthy controls. We hypothesize that D8/17 levels will be highest in the childhood-onset group, intermediate in the adult-onset group, and lowest in the healthy controls. 2) What is the relationship of D8/17 expression to clinical state? Forty D8/17 positive children with OCD/TS will be followed for clinical status, D8/17 expression, and evidence of streptococcal infection at 3-month intervals. 3) Is D8/17 positivity familial in childhood onset OCD/TS? Structured psychiatric interviews and D8/17 expression will be determined in all available biological first degree relatives of 40 probands with childhood onset OCD/TS and of 30 healthy controls. 4) Is D8/17 positivity a peripheral marker for risk of developing OCD/TS? Forty-eight unaffected (i.e., no evidence of OC/tic symptoms or RF) but D8/17 positive "at-risk" children and 48 controls (unaffected D8/17 negative children) will be followed prospectively for development of symptoms of OCD or TS as well as acute RF at 6-month intervals

描述（改编自申请人的摘要）：自身免疫性响应 据信链球菌抗原会产生风湿热（RF）， 包括其主要表现之一，是Sydenham的Chorea（SC）。 一个 遗传，发育和环境因素的相互作用决定了 对这些链球菌感染并发症的脆弱性。 瑞典等人 假设SC可能是某些形式的TIC和 强迫症（OCD）。 我们寻求一个可以的标记 确定OCD或Tourette综合征（TS）的几例以及多少病例可能 患有SC的病原体关系的疾病。 单克隆 抗体（MAB）D8/17识别A B细胞抗原，并在 所有RF的患者，有15％的RF患者亲属， 并在大约5个控件中。 人们认为这是一个特质标记 对RF的敏感性。 在我们的试点研究中，31名诊所患者7-24岁 参加儿童期强迫症和/或TS的岁月参加了岁月。 没有人携带 RF或SC的诊断。 所有患者的D8/17都是阳性的，而只有1个 21健康对照是阳性的。 这些发现表明D8/17 5月 作为儿童发作强迫症，TS的共同敏感性的标记 和SC。 拟议的研究将解决以下问题：1）是 D8/17特定于儿童期强迫症/TS的阳性？ D8/17的频率 45例儿童发作性强迫症/TS患者的队列中的积极性将为 相比之下，有30例成人OCD患者和30年龄/性别匹配的患者 健康控制。 我们假设D8/17水平在 童年发作组，成年人组中间，最低 健康控制。 2）D8/17表达与 临床状态？ 将遵循40个D8/17阳性儿童的OCD/TS儿童 对于临床状况，D8/17表达和链球菌的证据 以3个月的间隔感染。 3）是D8/17的阳性家族性 儿童发作OCD/TS？ 结构化精神访谈和D8/17 表达将在所有可用的生物学一级中确定 童年发作性强迫症和30个健康的40个概率的亲属 控件。 4）是D8/17阳性的外围标记 OCD/TS？ 四十八个未受影响（即，没有OC/TIC症状或RF的证据） 但是D8/17积极的“处于危险”儿童和48个对照（未受影响的D8/17） 负面的孩子）将被预期发展 OCD或TS的症状以及急性RF以6个月的间隔