Antibodies against three novel peptides in early axial spondyloarthritis patients from two independent cohorts

Abstract

Objective The aim of this study was to identify novel autoantibodies in axial spondyloarthritis (axSpA) and determine their diagnostic potential in early axSpA patients and controls from two independent cohorts.

Methods An axSpA cDNA phage display library was used to screen for novel immunoglobulin G (IgG) antibodies in plasma of early axSpA patients. Presence of these antibodies against novel Hasselt University (UH)‐axSpA peptides was determined in 76 early axSpA patients, 75 non‐specific chronic low back pain (CLBP) controls, 60 rheumatoid arthritis (RA) patients and 94 healthy controls (HC) from the UH cohort using enzyme‐linked immunosorbent assays (ELISA). Antibody reactivity was further validated in 174 axSpA patients from the Leuven Spondyloarthritis (Biologics) cohort ((Bio)SPAR), including 79 early axSpA patients.

Results We identified antibodies to 9 novel UH‐axSpA peptides, corresponding to randomly formed peptides and to a novel axSpA autoantigen, Double Homeobox protein 4 (DUX4). Antibodies to 3 UH‐axSpA peptides with the highest positive likelihood ratio (LR+) were significantly more present in early axSpA patients from the UH and (Bio)SPAR cohorts (14.2% (22/155)) compared to CLBP (5% (4/75)), resulting in 95% specificity. The LR+ for confirming axSpA using antibodies to these 3 UH‐axSpA peptides was 2.7, which is higher than the currently used laboratory marker C‐reactive protein (CRP). Testing for antibodies to these 3 UH‐axSpA peptides in CLBP increased post‐test probability for axSpA from 79% to 91%.

Conclusion Antibodies to 3 UH‐axSpA peptides could provide a novel tool for the diagnosis of a subset of axSpA patients.