Abstract
Axial spondyloarthritis (axSpA) is often diagnosed late due to the non-specific nature of its main symptom [chronic back pain (CBP)] and to the paucity of diagnostic markers, particularly in regions with low HLA-B27 prevalence, such as the Middle-East. We tested the performance of IgG4 and IgA anti-CD74 antibodies as an early diagnostic marker for axSpA, compared with the performance of HLA-B27, in Lebanon. Sera of axSpA patients diagnosed by the rheumatologist and also fulfilling the imaging arm of the ASAS criteria (patients) and of blood donors (BD) (controls) were analyzed for HLA-B27, IgG4 and IgA anti-CD74, blinded to clinical characteristics. Receiver Operating Characteristic curves were constructed to identify an optimal cut-off point for anti-CD74 antibodies. Diagnostic properties were calculated (sensitivity, specificity, positive, and positive predictive values (PPV, NPV), Likelihood ratios) for each marker. Forty-nine axSpA patients and 102 BD were included in the final analysis. IgA anti-CD74 correlated poorly with axSpA (Area Under the Curve (AUC) 0.657), whereas IgG4 anti-CD74 had a good discriminative value (AUC 0.837). Respectively, for HLA-B27, IgG4 anti-CD74, and the combination of both, we found a sensitivity of 33-92-33%, specificity of 96-79-98%, PPV 80-68-89%, NPV 75-95-75%, and LR+ 8.2-4.4-16.5. IgG4 anti-CD 74 were positive in 88% of HLA-B27 negative axSpA patients, and correlated with BASDAI. In this first study in a population with low HLA-B27 prevalence, IgG4 anti-CD74 antibodies combined with HLA-B27 showed higher diagnostic value than HLA-B27 alone for early axSpA. IgG4 anti-CD74 should be considered for further evaluation as an early axSpA diagnostic marker in future dedicated research, particularly in patients with CBP.
Highlights
MATERIALS AND METHODSAxial spondyloarthritis is often diagnosed late, due to the non-specific nature of its main symptom, chronic back pain (CBP) and to the paucity of diagnostic markers, and its pathogenesis is still unclear [1,2,3,4,5]
Classification criteria serve as surrogates for diagnosis in clinical practice and rely on CBP associated with either sacroiliitis on imaging or positive Human Leukocyte Antigen-B27 (HLAB27), in addition to other clinical or biological parameters [10, 11]
Eleven patients were excluded secondarily for the following reasons: axSpA was not confirmed by central reading of images in 6 cases, 2 patients had Armenian close ancestry and were considered as having a non-Lebanese genetic background, 2 patients had concomitant conditions that may have interfered with the antibodies levels and 1 patient had a longer disease duration than 3 years, discovered after referral to the study
Summary
Axial spondyloarthritis (axSpA) is often diagnosed late, due to the non-specific nature of its main symptom, chronic back pain (CBP) and to the paucity of diagnostic markers, and its pathogenesis is still unclear [1,2,3,4,5]. This association was recently studied in European patients with inflammatory back pain of ≤ 2 years duration and clinical suspicion of axSpA and found a sensitivity of Immunoglobulin A (Ig A) anti-CD74 of 47%, a specificity of 95.3% and a LR+ of 10.0 (International SpondyloArthritis autoantibody trial -InterSpA-) [23]. In this study (InterSpA-Lebanon), we tested the performance of IgG4 and IgA anti-CD74 as an early diagnostic markers for axSpA compared with the performance of HLA-B27 in Lebanon, which is known as one of the countries with the lowest HLA-B27 prevalence ever reported [15]. DNA of axSpA patients and BD were analyzed centrally for HLA-B27 genes (Polymerase Chain Reaction), without subtype analysis, and sera for IgA and IgG4 antibodies against CD74 by ELISA with specificity for CLIP (Class II-associated invariant chain peptide domain of the CD74 protein consisting of 25 amino-acids) developed in cooperation with AESKU.
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