FRI0312 ANTI-CD74 IGA ANTIBODIES ARE MOST SENSITIVE AND SPECIFIC TO IDENTIFY YOUNG MALE AXIAL SPONDYLOARTHRITIS PATIENTS
Authors: A. S. De Craemer, T. Witte, L. Deroo, T. Renson, P. Carron, F. Van den Bosch, X. Baraliakos, D. Elewaut
Journal: Annals of the Rheumatic Diseases (2020)

Background: CD74 is involved in the assembly of and the prevention of premature peptide-binding to major histocompatibility complex (MHC) class II. IgG autoantibodies directed against CD74 have been shown to be highly prevalent in patients with ankylosing spondylitis (AS). In contrast, conflicting results have been reported on the sensitivity and specificity of anti-CD74 IgA both in patients with non-radiographic axial spondyloarthritis (nr-axSpA) as well as AS. Objectives: To assess the performance of anti-CD74 IgA for identification of patients classified as nr-axSpA or AS compared to non-SpA controls. Methods: Serum samples of patients who were classified as having axial SpA according to the ASAS classification criteria, were collected at inclusion in the Be-Giant (a Belgian observational cohort enrolling patients in 7 peripheral and an academic hospital). Patients with chronic back pain of non-inflammatory origin and rheumatoid arthritis patients without back pain served as a control group. Serum aliquots were stored immediately after sampling at -80°C until further analysis. Anti-CD74 IgA antibodies were measured using the AESKULISA SpA Detect Kit (AESKU Diagnostics, Wendelsheim, Germany) as described in (1); values are expressed in U/mL. Analyses were restricted to patients ≤ 45 years of age who were anti-TNF naïve prior to inclusion. Results: Table 1 shows the patients’ demographic and clinical characteristics. Mean±SD anti-CD74 IgA concentration was significantly higher in AS (18.3±11.20) and nr-axSpA (19.3±12.6) compared to controls (9.8±6.35) (Figure 1). However, anti-CD74 IgA levels were higher in males than in females (p = 0.01) and in old (≥32 y/o) vs. younger patients (p = 0.13). Anti-CD74 IgA yielded an adjusted OR (95% CI) of 1.10 (1.03 – 1.19) for discrimination of nr-axSpA from controls. Table 2, which shows the performance of anti-CD74 IgA in 4 subgroups of patients divided by age and sex, shows that the highest AUC was seen in young male nr-axSpA patients. Similar results were found on the discrimination between AS patients and controls (AUC 0.827 in young males). Table 1. Demographic and clinical characteristics nr-axSpA AS control n = 150 n = 58 n = 14 Age, y (mean, SD) 31 (6.9) 32 (7.4) 30 (7.0) Male, n (%) 68 (45.3) 26 (44.8) 4 (28.5) Symptom duration, m (median, IQR) 35 (13 - 98) 111 (27 - 176) - HLA B27 positive, n (%) 103 (68.7) 48 (82.8) - Peripheral manifestations, n (%) 41 (27.3) 18 (31.0) - Extra-articular manifestations, n (%) 32 (21.3) 19 (32.8) - BASDAI (mean, SD) 4.4 (1.97) 4.1 (2.03) - CRP &gt; ULN, n (%) 45 (30.0) 33 (56.9) - Table 2. Performance of anti-CD74 IgA in discriminating nr-axSpA from controls, according to sex and age (young: &lt;32 y/o). AUC= area under the curve, PPV/NPV = positive/negative predictive value, LR+ = positive likelihood ratio. Cut-off (U/mL) AUC Sensitivity (%) Specificity (%) PPV (%) NPV (%) LR+ Male &amp; young 16.9 0.806 65.8 92.3 96.2 48.0 8.6 Male &amp; old 17.4 0.795 55.6 92.3 93.8 50.0 7.2 Female &amp; young 16.7 0.647 50.0 92.3 94.4 41.4 6.5 Female &amp; old 16.9 0.741 46.8 92.3 95.7 42.2 6.0 Figure 1. Univariate comparison of anti-CD74 IgA concentrations between nr-axSpA, AS and control patients (&lt;45 y/o). Conclusion: In this study, mean anti-CD74 IgA concentrations were higher in axial SpA patients compared to non-SpA controls. Application of this biomarker in young (&lt;32 y/o) male nr-axSpA or AS patients yielded the highest sensitivity and specificity. References: [1]Riechers E, Baerlecken N, Baraliakos X, et al. Sensitivity and Specificity of Autoantibodies Against CD74 in Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019;71(5):729-35. Acknowledgments: Aesku.Diagnostics (Wendelsheim, Germany) provided the ELISA kits. Disclosure of Interests: Ann-Sophie De Craemer: None declared, Torsten Witte: None declared, Liselotte Deroo: None declared, Thomas Renson: None declared, Philippe Carron: None declared, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Dirk Elewaut: None declared