Cell-based versus enzyme-linked immunosorbent assay for detection of anti-Tribbles homolog 2 autoantibodies in Chinese patients with narcolepsy

J Clin Sleep Med. 2024 Feb 6. doi: 10.5664/jcsm.11056. Online ahead of print.

Abstract

Study objectives: Narcolepsy type 1 (NT1) is attributed to a deficiency in cerebrospinal fluid orexin and is considered linked to autoimmunity. The levels of anti-Tribbles homolog 2 (TRIB2) autoantibodies are elevated in the sera of some patients with narcolepsy with cataplexy. Additionally, injecting mice with serum immunoglobulin from patients with narcolepsy with positive anti-TRIB2 antibodies can induce hypothalamic neuron loss and alterations in sleep patterns. Consequently, we hypothesized the existence of a potential association between anti-TRIB2 antibodies and narcolepsy. To test this possibility, we used cell-based assays (CBAs) and enzyme-linked immunosorbent assays (ELISAs) to detect the presence of anti-TRIB2 antibodies in Chinese patients with narcolepsy.

Methods: We included 68 patients with NT1; 39 patients with other central disorders of hypersomnolence; and 43 healthy controls (HCs). A CBA and a conventional ELISA were used to detect anti-TRIB2 antibody levels in patient sera.

Results: CBA was used to detect serum anti-TRIB2 antibodies in Chinese patients with narcolepsy, and the results were negative. However, when the ELISA was used, only two NT1 patients had TRIB2 antibody titers higher than the mean titer plus 2 SD of the HCs.

Conclusions: In our study, ELISA identified TRIB2 autoantibodies in sera of narcolepsy patients where CBA failed to demonstrate them. Contrary to our hypothesis, this intriguing finding deserves further research to elucidate the potential association between TRIB2 and NT1. Exploring the implications of TRIB2 autoantibodies in narcolepsy and disparate outcomes between ELISA and CBA could provide crucial insights.

Keywords: CBA; ELISA; TRIB2; Tribbles homolog 2; autoantibodies; cell-based assay; enzyme-linked immunosorbent assay; narcolepsy.