Identification and validation of narcolepsy-spesific autoantibodies with immunoprecipitation and mass spectrophotometry

Narcolepsy is a chronical sleep disorder characterized by abnormal transition to rapid eye movement (REM) phase with sudden onset of excessive daytime sleepiness, disrupted nighttime sleep, catalexy and hypnagogic/hypnopompic hallucinations. The first symptoms of this disease (approximately 1 in 2000) begin in adolescence and young adulthood. The most important etiology is the loss of neurons producing hypocretin hormone related to wakefulness. Furthermore, the connection with human leukocyte antigens (HLA) suggests that narcolepsy may be an autoimmune disorder. In this thesis, it was aimed to detect and validate the immune mechanisms, disease-specific candidate molecule/molecules that may affect the pathogenesis of narcolepsy. Thus, the goal was to obtain important data for the evaluation of narcolepsy as an autoimmune disease and to pioneer new treatment goals. Immunoprecipitation and Liquid Chromatography-Mass Spectrometry (LC-MS) studies were carried out with narcolepsy group sera. According to the results of the analysis, complement component 4 binding protein alpha (C4BPA) was detected as a candidate antigen in narcolepsy. In the validation studies, it was aimed to show the levels of C4BPA and antibodies developed against C4BPA in the patient and healthy control sera. 41 patients with narcolepsy and 19 healthy controls were included. When narcolepsy and healthy control samples were compared, the level of C4BPA was found significantly higher in healthy controls than narcolepsy patients. Anti-C4BPA levels were also compared. Although no significant difference was detected, narcolepsy cases seemed to have higher levels of anti-C4BPA compared to healthy subjects. Even though validation studies were considered to evaluate the presence of immune complexes instead of anti-C4BPA formation, the results of the study showed that the mechanisms of innate immunity, which may cause autoimmunity, might have an effective role in the etiopathogenesis of narcolepsy. For this reason, further validation studies are required for the detection of disease specific autoantibodies.