The autoantibody in the sera as biological markers of developmental neuropsychiatric disorders

• Main Authors: Yeh, Chin-Bin, 葉啟斌
• Other Authors: Shyu, Jia-Fwa
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/67084546445681692511

博士 === 國防醫學院 === 醫學科學研究所 === 100 === Tourette’s syndrome (TS) and attention deficit hyperactivity disorder (ADHD) are developmental neuropsychiatric disorder and often comorbid other neuropsychiatric disorders, for example, the patients with TS often comorbid obsessive-compulsive disorder (OCD) and ADHD, and the patients with ADHD often comorbid developmental coordination disorder (DCD).The comorbidity of other neuropsychiatric disorder often interferes with early recognition and complicated the treatment strategy of the patients with TS or ADHD. Our aim was to identify the biological markers of these patients. We first identified the disease-specific autoantigen in peripheral blood serum using immunological experiment for the patients with TS. It will help to investigate the underlying mechanisms of TS which autoimmunity involved. We recruited the patients with TS or ADHD by interviewing them with the Kiddie-Schedule for Affective Disorders and Schizophrenia-epidemiology version (K-SADS-E) to make the diagnosis. For the measurement of disease-specific autoantibody in peripheral blood of the patients with TS, there were 32 patients with TS, 47 patients with ADHD and 14 healthy controls recruited. The immunological assay for the serum between TS group and other two groups including immunoprecipitation (IP), enzyme-linked immunosorbent assay (ELISA) were done. In the immunological study, the immunoprecipitation of serum from the patients with TS and neuronal cells revealed significant different expression of 120 kDa protein in Western blot analysis between TS group and the control groups. The Mass Spectrum analysis of the in-gel digestion of the 120 kDa found that there were 31% of the sequence matched with a novel membrane protein hyperpolarisation-activated cyclic nucleotide channel 4 (HCN4). The higher level of HCN4 antibody in the serum of TS group compared to the other two groups was further validated with ELISA and immunoflourescent staining. The more frequency of stereotype behaviors was found after the administration of sera from the patients with TS or anti-HCN4 antibody into the striatum of rats’ brain. Our findings help physicians to recognize the disease-specific pathophysiology earlier by the ways of exploring of the biological markers for those developmental neuropsychiatric disorders. It provides a clue for future intervention for those patients.