FRI0363 AUTOANTIBODIES TO THREE NOVEL PEPTIDES IN EARLY AXIAL SPONDYLOARTHRITIS IN TWO INDEPENDENT COHORTS
Authors: Dana Quaden, Patrick Vandormael, Piet Geusens, Johan Vanhoof, Kurt de Vlam, Veerle Somers
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Diagnosis of axial spondyloarthritis (axSpA) is challenging since clinical manifestations, such as inflammatory back pain, peripheral arthritis, enthesitis and inflammatory bowel disease, often overlap with other disorders. Current laboratory markers for axSpA, Human Leukocyte Antigen (HLA)-B27 and C-reactive protein (CRP) are not sufficiently specific for diagnosis. Despite being considered a "seronegative" disease, emerging evidence supports the involvement of antibodies in axSpA. In order to identify novel autoantibodies in axSpA patients, we recently screened an axSpA cDNA phage display library for reactivity with immunoglobulin G (IgG) antibodies in plasma of early axSpA patients. This resulted in autoantibodies to 9 novel University of Hasselt (UH) axSpA peptide targets, corresponding to fragments of known proteins and novel lineair peptides. <h3>Objectives</h3> The aim of this study was to determine the diagnostic potential of autoantibodies to the 9 novel UH axSpA peptides in axSpA patients and controls from 2 independent cohorts. <h3>Methods</h3> Using enzyme-linked immunosorbent assays (ELISA), presence of antibodies to the 9 UH axSpA peptides expressed on phage particles was determined in 76 early axSpA patients, 75 chronic low back pain patients (LBP), 60 early rheumatoid arthritis patients (RA) and 94 healthy controls (HC) from the UH cohort. Antibody reactivity was further validated in 174 patients from the <b>Leuven</b> Spondyloarthritis (Biologics) Cohort ((<b>Bio)SPAR</b>), including 79 early axSpA patients. <h3>Results</h3> Antibody reactivity against at least one of 9 novel UH axSpA peptides was found in 54% (41/76) of early axSpA patients, 26% (24/94) of HC (<i>p=</i><i>0.0002</i>), 39% (29/75) of LBP (<i>p=</i><i>0.0731</i>) and 38% (23/60) of RA patients (<i>p=</i><i>0.0845</i>) from the UH cohort, as compared to 43% (74/174) of the axSpA patients from the (Bio)SPAR cohort. By combining the three UH axSpA peptides with highest positive likelihood ratios (LR+) into a panel, antibodies against these 3 peptides were detected in 14.2% (22/155) of early axSpA patients from the combined UH and (Bio)SPAR cohorts and in only 5% (4/75) of persons with LBP (<i>p=</i><i>0.</i>0484), resulting in a specificity of 95%.. The LR+ for confirming axSpA using antibodies to these 3 UH axSpA peptides was 2.7, which is the same as for the currently used laboratory marker CRP. Assuming a 5% pretest probability of axSpA in persons with LBP, a combination of the presence of inflammatory back pain (LR+ 3.1) and a positive test result for the laboratory markers HLA-B27 (LR+ 9.0) and CRP (LR+ 2.5) provides a disease (posttest) probability of 79%. When we added a positive test result for the presence of antibodies to the 3 UH axSpA peptides (LR+ 2.7), posttest probability could be increased to 91%. <h3>Conclusion</h3> Antibodies to 3 UH axSpA peptides were significantly more present in early axSpA patients compared to LBP and could provide a novel tool for objective diagnosis of a subset of axSpA patients. <h3>Disclosure of Interests</h3> Dana Quaden: None declared, Patrick Vandormael: None declared, Piet Geusens Grant/research support from: Research support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Grant/research support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Consultant for: Research support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Speakers bureau: Research support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Speakers bureau: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Johan Vanhoof: None declared, Kurt de Vlam Consultant for: Pfizer Inc, Consultant for: Johnson &amp; Johnson, Veerle Somers Grant/research support from: Research support from Bristol Myers-Squibb