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VOLUME 33, ISSUE 07

RAPID PUBLICATIONS
Anti-Tribbles Homolog 2 (TRIB2) Autoantibodies in Narcolepsy are Associated with Recent Onset of Cataplexy

Minae Kawashima, PhD1; Ling Lin, MD, PhD1; Susumu Tanaka, PhD2; Poul Jennum MD, Dr. Med. Sci.3; Stine Knudsen, MD, PhD3; Sona Nevsimalova, MD4; Giuseppe Plazzi, MD5; Emmanuel Mignot, MD, PhD1

1Center for Narcolepsy, Stanford University School of Medicine, Palo Alto, CA; 2The Sleep Disorders Research Project, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan; 3Danish Center for Sleep Medicine, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark; 4Department of Neurology, Charles University in Prague, 1st Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic; 5Sleep Disorders Center, Department of Neurological Sciences, University of Bologna, Bologna, Italy



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Study Objective: Recent studies have found increased autoantibodies against Tribbles homolog 2 (anti-TRIB2) and anti-streptolysin O (ASO) in narcolepsy. In this study, we replicated this finding with a primary focus on recent onset cases.
Participants and Methods: Participants included (1) 90 cases with cataplexy, (2) 57 cases without cataplexy, and (3) 156 age-sex matched controls, including 73 human leukocyte antigen (HLA)-DQB1*0602 allele carriers. A radioligand binding assay was used to detect anti-TRIB2 antibodies.
Results: Anti-TRIB2 antibodies were prevalent in HLA-DQB1*0602 positive cases with cataplexy (25.0% of 76) and rare in cases without cataplexy (3.5% of 57, OR = 9.2, 95% CI = 2.5 - 33.5, P = 6.0 x 10-4) or controls (4.5% of 156, OR = 7.1, 95% CI = 3.1 - 16.2, P = 9.3 x 10-6). Anti-TRIB2 positivity in controls was not associated with DQB1*0602. In DQB1*0602 narcolepsy-cataplexy cases, the presence of anti-TRIB2 was associated with short disease duration (2.3 years from cataplexy onset), with 41.0% positive in this group (OR = 7.4 versus cases with onset > 2.3 years, 95% CI = 1.9 - 28.5, P = 9.0 x 10-4). Anti-TRIB2 positivity in 39 DQB1*0602 positive recent onset cases was associated with increased ASO antibody (> 200 IU) (OR = 6.2, 95% CI = 1.6 - 24.6, P = 0.01), but did not correlate with age, gender, or body mass index.
Conclusion: Anti-TRIB2 autoantibodies are strongly associated with narcolepsy close to cataplexy onset (≤ 2.3 years). Anti-TRIB2 was rarely found in cases without cataplexy or with distant onset.
Keywords: Human narcolepsy, Tribbles homolog 2 (TRIB2), autoantibody, anti-streptolysin O (ASO)

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