Human Leukocyte Antigen-Typing in Patients with Excessive Daytime Sleepiness
AbstractBackground and Objective: Narcolepsy is a disorder recognized by excessive daytime sleepiness (EDS). Several studies demonstrated its association with human leukocyte antigen (HLA) DQB1*0602, DQA1*0102, and DRB1*15. Our study aimed to perform HLA-typing on patients with EDS. Moreover, we performed HLA-typing for family members of the patients.Materials and Methods: We studied 83 patients with EDS and 77 of their first-degree relatives. Patients filled out a questionnaire including Epworth Sleepiness Scale (ESS), and underwent polysomnography (PSG) and multiple sleep latency test (MSLT). The whole blood samples were drawn from the patients and their families for HLA typing (class II). International classification of sleep disorders-2 (ICSD-2) criteria was used as the gold standard for diagnosing narcolepsy.Results: HLA DQB1*0602 was present in 20 (45.5%) of narcoleptic patients and 2 (5.1%) of patients with other causes of EDS. Prevalence of DQB1*0602 in family members of narcoleptic patients were higher than family members of patients with other causes of EDS (38% vs. 11.1%, P = 0.06). DQB1*0602, DQA1*0102, and DRB1*15 were more prevalent in narcoleptic patients with cataplexy than narcoleptic patients without cataplexy and patients with other causes of EDS. The sensitivities of the DQB1*0602 for diagnosing narcolepsy, narcolepsy with cataplexy, and narcolepsy without cataplexy were 40%, 60%, and 20%, respectively; while specificities were 93.9%, 87.9%, and 70.6%, respectively. Conclusion: HLA typing can be helpful in patients with atypical cataplexy and inconclusive MSLT results. More studies of Iranian narcoleptic patients are required for analyzing their HLA sequences.
Hong SC, Lin L, Jeong JH, et al. A study of the diagnostic utility of HLA typing, CSF hypocretin-1 measurements, and MSLT testing for the diagnosis of narcolepsy in 163 Korean patients with unexplained excessive daytime sleepiness. Sleep 2006; 29: 1429-38.
Debebe DG, Sadeghniat-Haghighi K, Shakiba Y, et al. Th17 cell related cytokine profiles in narcolepsy and other types of excessive daytime sleepiness. J Sleep Sci 2016; 1: 44-50.
De la Herran-Arita AK, Garcia-Garcia F. Narcolepsy as an immune-mediated disease. Sleep Disord 2014; 2014: 792687.
Ohayon MM. Narcolepsy is complicated by high medical and psychiatric comorbidities: A comparison with the general population. Sleep Med 2013; 14: 488-92.
Mignot E, Lin L, Rogers W, et al. Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. Am J Hum Genet 2001; 68: 686-99.
Chen YH, Huang YS, Chien WH, et al. Association analysis of the major histocompatibility complex, class II, DQ beta1 gene, HLA-DQB1, with narcolepsy in Han Chinese patients from Taiwan. Sleep Med 2013; 14: 1393-7.
Ollila HM, Ravel JM, Han F, et al. HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy. Am J Hum Genet 2015; 96: 136-46.
Mignot E, Hayduk R, Black J, et al. HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients. Sleep 1997; 20: 1012-20. 9. American Sleep Disorders Association. The international classification of sleep disorders: diagnostic and coding manual. Washington, DC: American Sleep Disorders Association; 1990.
Chen L, Fong SY, Lam CW, et al. The familial risk and HLA susceptibility among narcolepsy patients in Hong Kong Chinese. Sleep 2007; 30: 851-8.
Sadeghniiat Haghighi K, Montazeri A, Khajeh Mehrizi A, et al. The Epworth sleepiness scale: Translation and validation study of the Iranian version. Sleep Breath 2013; 17: 419-26.
Alaez C, Lin L, Flores A, et al. Association of narcolepsy-cataplexy with HLA-DRB1 and DQB1 in Mexican patients: A relationship between HLA and gender is suggested. BMC Med Genet 2008; 9: 79.
Geremew D, Rahimi-Golkhandan A, Sadeghniiat-Haghighi K, et al. Association study of HLADQB1*0602 allele in Iranian patients with narcolepsy. Iran J Allergy Asthma Immunol 2017; 16: 452-6.