SCREENING FOR IMMUNOGLOBULIN A ANTIBODY REACTIVITY IN EARLY AXIAL SPONDYLOARTHRITIS IDENTIFIES NOVEL ANTIGENIC TARGETS

Abstract

Background: Although autoantibodies are not generally considered to be a hallmark of axial spondyloarthritis (axSpA), increasing evidence suggests the presence of autoantibodies in a subset of axSpA patients. Most of these described antibodies are of the immunoglobulin G (IgG) isotype while other antibody isotypes are less well studied. Antibodies of the IgA isotype can be of interest due to the strong link between gut inflammation and spondyloarthropathies.

Objectives: The aim of this study was to identify and characterize novel IgA isotype (auto)antibodies specific for early axSpA patients.

Methods: An axSpA cDNA phage display library, representing the antigenic repertoire from axSpA hip synovium, was constructed and screened for reactivity with IgA antibodies in plasma of early axSpA patients (n=10). Using enzyme-linked immunosorbent assays (ELISA), antibody reactivity against 173 identified targets was initially determined in pooled plasma of early axSpA patients (n=60) and healthy controls (HC, n=30), collected at Hasselt University. Antigenic targets that showed increased IgA reactivity in axSpA plasma pools were further validated in individual plasma samples of early axSpA patients (n=79) and HC (n=101).

Results: We identified 10 novel Hasselt University (UH) axSpA peptide targets with increased IgA antibody reactivity in pooled axSpA plasma. At present, validation of 8 UH-axSpA-IgA peptide targets in individual plasma samples revealed antibody reactivity against at least one of these targets in 32% of early axSpA patients (25/79) compared to 26% in HC (31/101, p=0.4082). By combining the 3 UH-axSpA-IgA peptides with the highest positive likelihood ratio (LR+) into a panel, an increased overall specificity of 90% (10/101) could be achieved, with an associated sensitivity of 24% (19/79, p=0.0138) resulting in a LR+ of 2.4. Antibody reactivity testing of the remaining 2 UH-axSpA-IgA peptide targets is currently ongoing.

Conclusion: The increased reactivity of IgA (auto)antibodies against several novel antigenic peptide targets underscores the role of the humoral immune response in axSpA, and might indicate a potential link with mucosal inflammation. IgA antibody reactivity against these novel peptide targets will be further validated in independent cohorts of early axSpA patients as well as in patients with chronic low back pain.

Disclosure of Interests: Patrick Vandormael: None declared, Dana Quaden: None declared, Pieter Ruytinx: None declared, Joyce Janssens: None declared, Johan Vanhoof: None declared, Piet Geusens Grant/research support from: Pfizer, Abbott/Abbvie, Janssen, Celgene, Lilly, Amgen, MSD, UCB, Will, Roche, BMS, Novartis, Sanofi, Consultant of: Pfizer, Abbott/Abbvie, Janssen, Celgene, Lilly, Amgen, MSD, UCB, Will, Roche, BMS, Novartis, Sanofi, Veerle Somers Grant/research support from: Research grant from Pfizer and BMS