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临床试验/NCT04084977
NCT04084977Unknown不适用

Sydenham's Chorea: Is There a Link Between Neuropsychiatric Symptoms and Anti-dopamine Receptor Autoantibodies?

Shaare Zedek Medical Center1 个研究点 分布在 1 个国家目标入组 100 人开始时间: 2016年7月1日最近更新:
适应症

试验速览

阶段
不适用
入组人数
100
试验地点
1
主要终点
Antibody titers

研究概览

简要总结

Sydenham's chorea (SC) is a post-streptococcal, neuropsychiatric disorder associated with anti-neuronal antibodies. The investigators demonstrated elevated anti-D1-receptor (D1R) and anti-D2-receptor (D2R) antibodies titers compared to controls using ELISA. Similarly, the investigators found antibodies to surface D2R in neuropsychiatric, autoimmune disorders, including SC using cell-based assays. The investigators hypothesize that these autoantibodies cause neuropsychiatric symptoms by inducing intracellular signaling changes resulting in altered dopaminergic neurotransmission. To check this, the investigators will test whether sera from patients with SC alter dopaminergic signaling pathways. The investigators will examine sera from 30 SC patients with active symptoms and 30 age-matched healthy controls. Patients with SC will be assessed for severity of neuropsychiatric symptoms using UFMG Sydenham's Chorea Rating Scale. Controls with evidence of streptococcal infections or autoimmune disorders will be excluded. Sera will be examined for anti-D1R and anti-D2R antibodies. Signaling studies will assess sera impact on 1) calcium/calmodulin-dependent protein kinase II activity in human neuronal cells. 2) dopamine D1/D2 receptors signaling using cAMP assays in transfected cell lines. The investigators will examine the correlation between modified signaling and clinical symptoms.

详细描述

Participants:

The investigators will enroll participants with acute Sydenham's chorea (aSC) and age-matched controls with streptococcal tonsillitis (ST) within the past 4 months and healthy children (HC) with no a history of a strep infection in the past 6 months and negative throat culture. Informed consent will be obtained from participants and/ or parents. Children with SC will be evaluated for SC severity using the USCRS. The investigators will record clinical data regarding gender, age, duration symptoms, and medical treatments. Controls will be examined by referring physician to rule out chorea. Sera samples from all participants will be stored at -70°C and shipped to the microbiology and immunology lab, University of Oklahoma Health Sciences Center (OHSC) on dry ice.

Laboratory testing:

Immunophenotyping for anti-D1R, anti-D2R, anti- LG and anti-tubulin titers and signaling studies will be performed at the OUHSC microbiology and immunology laboratory.

Autoantibody titers. Sera will be assayed for reactivity with the dopamine D1 and D2 receptors (Human dopamine D1 and D2 receptor membrane antigens, Perkin Elmer-Membrane Target Systems) in the direct ELISA and assays which include the ELISA competitive inhibition. Anti- LG and anti-tubulin titers will be tested as well.

研究设计

研究类型
Observational
观察模型
Case Control
时间视角
Retrospective

入排标准

年龄范围
2 Years 至 40 Years(Child, Adult)
接受健康志愿者

入选标准

  • sydenham chora OR strep tonsilitiscontrol without strep tonsilitis OR

排除标准

  • neurological disrder autoimmune disorder

结局指标

主要结局

Antibody titers

时间窗: Once at time of initial visit within the first 4 months from onset

titer levels of anti dopamine receptors (anti-D1 and anti-D2) using ELISA (titer levels are expresed as dilutions i.e. 1:400)

UFMG Sydenham's Chorea Rating Scale

时间窗: Upon presentation when symptomatic, usually within 4 months of onset

the mean value of the 21 item of clinical chorea rating. Ranging from 0 (=none) to 4 (=severe) for each item

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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