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

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

Minae Kawashima et al. Sleep. 2010 Jul.

Abstract

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 (< or = 2.3 years). Anti-TRIB2 was rarely found in cases without cataplexy or with distant onset.

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Figures

Figure 1
Figure 1

Anti-TRIB2 autoantibody Index in narcolepsy and control sera. Anti-TRIB2 autoantibody reactivity index is shown in narcolepsy with cataplexy, narcolepsy without cataplexy, and age-gender matched controls. Each dot represents one individual. The cutoff value at mean + 2SD is shown as the dotted line (1.22). Values above this line are considered positive. P values were calculated using Fisher's exact tests. HLA-DQB1*0602 positive, ● negative, ○; * alikely HCRT deficiency (< 110 pg/mL); *blikely normal HCRT (> 200 pg/mL).

Figure 2
Figure 2

The presence of anti-TRIB2 autoantibodies is strongly associated with disease duration. Seventy-six narcolepsy-cataplexy patients were tested. Each dot corresponds to one individual. Anti-TRIB2 indices are plotted as a function of disease duration (age at blood sample collection minus age at onset of cataplexy). Positives have values above 1.22 (see Figure 1). Note that all but 2 positives are disease duration ≤ 2.3 years (best discriminant value using quality receiver operating characteristic curve). The dotted line delineates 2.3 years. Subjects with disease duration below 2.3 years are called recent onset.

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