Elevated Anti-Streptococcal Antibodies in Patients with Recent Narcolepsy Onset

Abstract

STUDY OBJECTIVES: Narcolepsy-cataplexy has long been thought to have an autoimmune origin. Although susceptibility to narcolepsy, like many autoimmune conditions, is largely genetically determined, environmental factors are involved based on the high discordance rate (approximately 75%) of monozygotic twins. This study evaluated whether Streptococcus pyogenes and Helicobacter pylori infections are triggers for narcolepsy. DESIGN: Retrospective, case-control. SETTING: Sleep centers of general hospitals. PARTICIPANTS: 200 patients with narcolepsy/hypocretin deficiency, with a primary focus on recent onset cases and 200 age-matched healthy controls. All patients were DQB1*0602 positive with low CSF hypocretin-1 or had clear-cut cataplexy. MEASUREMENTS AND RESULTS: Participants were tested for markers of immune response to beta hemolytic streptococcus (anti-streptolysin O [ASO]; anti DNAse B [ADB]) and Helicobacter pylori [Anti Hp IgG], two bacterial infections known to trigger autoimmunity. A general inflammatory marker, C-reactive protein (CRP), was also studied. When compared to controls, ASO and ADB titers were highest close to narcolepsy onset, and decreased with disease duration. For example, ASO > or = 200 IU (ADB > or = 480 IU) were found in 51% (45%) of 67 patients within 3 years of onset, compared to 19% (17%) of 67 age matched controls (OR = 4.3 [OR = 4.1], P < 0.0005) or 20% (15%) of 69 patients with long-standing disease (OR = 4.0 [OR = 4.8], P < 0.0005]. CRP (mean values) and Anti Hp IgG (% positive) did not differ from controls. CONCLUSIONS: Streptococcal infections are probably a significant environmental trigger for narcolepsy.