Diagnostic criteria for narcolepsy and HLA‐DR2 frequencies

Matsuki, Kazumasa; Honda, Yoshiyuki; Juji, Takeo

doi:10.1111/j.1399-0039.1987.tb01614.x

Cited by 32 publications

(12 citation statements)

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“…There were some observed differences in the frequency of DRB1 * 1501 , DQA1 * 0102 , and DQB1 * 0602 among previous studies on narcolepsy patients [2, 8, 9]. These differences have been proposed to be due to differences in the diagnostic criteria, including the presence of cataplexy, the ethnic origin of the patient groups, and the resolution of the HLA-typing method [2, 19-21]. Even the frequency of DQB1 * 0602 in Korean narcoleptic patients with cataplexy from previous reports and this study varied from 86.4% to 100% [9].…”

Section: Discussionmentioning

confidence: 83%

“…In previous reports, DRB1 * 1501-DQB1 * 0602 and DQA1 * 0102-DQB1 * 0602 have been shown to display a high degree of linkage disequilibrium in the Korean population [12, 13, 15]. There were some observed differences in the frequency of DRB1 * 1501 , DQA1 * 0102 , and DQB1 * 0602 among previous studies on narcolepsy patients [2, 8, 9]. These differences have been proposed to be due to differences in the diagnostic criteria, including the presence of cataplexy, the ethnic origin of the patient groups, and the resolution of the HLA-typing method [2, 19-21].…”

Section: Discussionmentioning

confidence: 92%

“…Previous studies have demonstrated that the presence of DQB1 * 0602 is reduced among patients in whom cataplexy is absent or ill defined [6, 7]. Differences in the frequency of certain HLA alleles have been observed in previous reports, and these differences have been suggested to be associated with ethnic origin and other factors, including the diagnostic criteria used to identify narcolepsy [2, 8, 9]. More specifically, the frequency and influence of DR2 has been reported to differ according to ethnic origin and the resolution of the HLA typing method.…”

Section: Introductionmentioning

confidence: 99%

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Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

et al. 2012

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BackgroundNarcolepsy is a neurologic disorder characterized by excessive daytime sleepiness, symptoms of abnormal rapid eye movement (REM) sleep, and a strong association with HLA-DRB1*1501, -DQA1*0102, and -DQB1*0602. Here, we investigated the clinico-physical characteristics of Korean patients with narcolepsy, their HLA types, and the clinical utility of high-resolution PCR with sequence-specific primers (PCR-SSP) as a simple typing method for identifying DRB1*15/16, DQA1, and DQB1 alleles.MethodsThe study population consisted of 67 consecutively enrolled patients having unexplained daytime sleepiness and diagnosed narcolepsy based on clinical and neurological findings. Clinical data and the results of the multiple sleep latency test and polysomnography were reviewed, and HLA typing was performed using both high-resolution PCR-SSP and sequence-based typing (SBT).ResultsThe 44 narcolepsy patients with cataplexy displayed significantly higher frequencies of DRB1*1501 (Pc= 0.003), DQA1*0102 (Pc=0.001), and DQB1*0602 (Pc=0.014) than the patients without cataplexy. Among patients carrying DRB1*1501-DQB1*0602 or DQA1*0102, the frequencies of a mean REM sleep latency of less than 20 min in nocturnal polysomnography and clinical findings, including sleep paralysis and hypnagogic hallucination were significantly higher. SBT and PCR-SSP showed 100% concordance for high-resolution typing of DRB1*15/16 alleles and DQA1 and DQB1 loci.ConclusionsThe clinical characteristics and somnographic findings of narcolepsy patients were associated with specific HLA alleles, including DRB1*1501, DQA1*0102, and DQB1*0602. Application of high-resolution PCR-SSP, a reliable and simple method, for both allele- and locus-specific HLA typing of DRB1*15/16, DQA1, and DQB1 would be useful for characterizing clinical status among subjects with narcolepsy.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

et al. 2012

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“…Interestingly, the association with DQB1*0602 is extremely strong only in subjects with typical cataplexy [16,17], most of which also have low CSF hypocretin [13]. The DQB1*0602 association is decreased or absent in subjects without cataplexy.…”

Section: Introductionmentioning

confidence: 99%

DQB10301 and DQB10601 Modulate Narcolepsy Susceptibility in Koreans

Hong

Lin

et al. 2007

Human Immunology

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“…The result was nonetheless remarkable: over 95 % of cases with cataplexy carried DR2, DQ1 versus 25 % in general Caucasian and Japanese populations [37, 42]. Using another technique, mixed leukocyte culture (MLC), DR2 antigens were found to be heterogeneous, including Dw12, Dw2, Dw21, and Dw22 subtypes [43, 44].…”

Section: First Hla Association Studies In Narcolepsy and Early Immunomentioning

confidence: 99%

History of narcolepsy at Stanford University

Mignot

2014

Immunol Res

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Although narcolepsy was first described in the late nineteenth century in Germany and France, much of the research on this disorder has been conducted at Stanford University, starting with Drs. William C. Dement and Christian Guilleminault in the 1970s. The prevalence of narcolepsy was established, and a canine model discovered. Following the finding in Japan that almost all patients with narcolepsy carry a specific HLA subtype, HLA-DR2, Hugh Mac Devitt, F. Carl Grumet, and Larry Steinman initiated immunological studies, but results were generally negative. Using the narcoleptic canines, Dr. Nishino and I established that stimulants increased wakefulness by stimulating dopaminergic transmission while antidepressants suppress cataplexy via adrenergic reuptake inhibition. A linkage study was initiated with Dr. Grumet in 1988, and after 10 years of work, the canine narcolepsy gene was cloned by in 1999 and identified as the hypocretin (orexin) receptor 2. In 1992, studying African Americans, we also found that DQ0602 rather than DR2 was a better marker for narcolepsy across all ethnic groups. In 2000, Dr. Nishino and I, in collaboration with Dr. Lammers in the Netherlands, found that hypocretin 1 levels in the cerebrospinal fluid (CSF) were undetectable in most cases, establishing hypocretin deficiency as the cause of narcolepsy. Pursuing this research, our and Dr. Siegel’s group, examining postmortem brains, found that the decreased CSF hypocretin 1 was secondary to the loss the 70,000 neurons producing hypocretin in the hypothalamus. This finding revived the autoimmune hypothesis but attempts at demonstrating immune targeting of hypocretin cells failed until 2013. At this date, Dr. Elisabeth Mellins and I discovered that narcolepsy is characterized by the presence of autoreactive CD4+ T cells to hypocretin fragments when presented by DQ0602. Following reports that narcolepsy cases were triggered by vaccinations and infections against influenza A 2009 pH1N1, a new pandemic strain that erupted in 2009, our groups also established that a small epitope of pH1N1 resembles hypocretin and is likely involved in molecular mimicry. Although much remains to be done, these achievements, establishing hypocretin deficiency as the cause of narcolepsy, demonstrating its autoimmune basis, and showing molecular mimicry between hypocretin and sequences derived from a pandemic strain of influenza, are likely to remain classics in human immunology.

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Diagnostic criteria for narcolepsy and HLA‐DR2 frequencies

Cited by 32 publications

References 12 publications

Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

DQB10301 and DQB10601 Modulate Narcolepsy Susceptibility in Koreans

History of narcolepsy at Stanford University

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Diagnostic criteria for narcolepsy and HLA‐DR2 frequencies

Cited by 32 publications

References 12 publications

Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

DQB1*0301 and DQB1*0601 Modulate Narcolepsy Susceptibility in Koreans

History of narcolepsy at Stanford University

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DQB10301 and DQB10601 Modulate Narcolepsy Susceptibility in Koreans