Anti-Tribbles homolog 2 (TRIB2) autoantibodies in narcolepsy are associated with recent onset of cataplexy.
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.


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.


CONCLUSIONS
Anti-TRIB2 autoantibodies are strongly associated with narcolepsy close to cataplexy onset (< or = 2.3 years). Anti-TRIB2 was rarely found in cases without cataplexy or with distant onset.
Kawashima
Minae
M
Center for Narcolepsy, Stanford University School of Medicine, 701-B Welch Road, Palo Alto, CA 94304, USA. mina-e@umin.ac.jp
Lin
Ling
L
Tanaka
Susumu
S
Jennum
Poul
P
Knudsen
Stine
S
Nevsimalova
Sona
S
Plazzi
Giuseppe
G
Mignot
Emmanuel
E
D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002385:Cataplexy / Q000150:complications*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D008297:Male; D009290:Narcolepsy / Q000276:immunology*; D016017:Odds Ratio; D011869:Radioligand Assay / Q000379:methods
D001323:Autoantibodies; D047908:Intracellular Signaling Peptides and Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human