脑脊液食欲素-A 放射免疫分析的方法学评价与比较：建立 1 型发作性睡病临界值并探索遗传与临床特征

Background This study aimed to evaluate an in-house radioimmunoassay (RIA) for cerebrospinal fluid (CSF) orexin-A measurement, establish a diagnostic cut-off for narcolepsy type 1 (NT1), explore associations with HLA genotype, assess the significance of intermediate orexin-A levels, and compare post-H1N1 Pandemrix-vaccinated and sporadic cases of NT1 and NT2. Methods Control samples were utilized to compare the performance of the in-house RIA method developed at Sahlgrenska University Hospital with the commercial Phoenix Pharmaceuticals RIA kit. CSF samples from individuals evaluated for central hypersomnolence disorders were analyzed using both RIA kits. Diagnostic thresholds, intermediate orexin-A levels, and associations with HLA-DQB1*06:02 and Pandemrix vaccination were assessed. Clinical and demographic data were also collected. Results The in-house RIA yielded significantly higher orexin-A levels in controls (540.5 ± 166.9 pg/mL) than the Phoenix kit (369.2 ± 96.2 pg/mL), with a mean ratio of 1.54. The in-house method established a diagnostic cut-off for NT1 of 153 pg/mL (100% sensitivity, 95.9% specificity), approximately 38% higher than the standard cut-off. Intermediate orexin-A levels (153-400 pg/mL) were found in 9.7% of cases and were associated with HLA-DQB1*06:02 positivity. In the cohort, 75.9% with NT1 had been vaccinated with Pandemrix. Clinical features were similar between vaccinated and sporadic narcolepsy cases. Conclusion The in-house RIA method is reliable and yields higher orexin-A levels than the commercial kit. Intermediate levels were linked to HLA-DQB1*06:02, suggesting shared pathological mechanisms. The study was not designed to examine an association between Pandemrix vaccination and the onset of NT1 or NT2.