OP0041 SALIVA AND SERUM LEVELS OF CXCL13: ASSOCIATION WITH THE SEVERITY OF SALIVARY GLAND LESIONS AND LYMPHOMA IN PATIENTS WITH SJÖGREN’S SYNDROME (SS)
Authors: L. Chatzis, A. Goules, A. Tzioufas, E. Kapsogeorgou
Journal: Annals of the Rheumatic Diseases (2021)

Background: CXCL13 has been implicated in the formation of ectopic germinal centers (GC) in minor salivary gland (MSG) inflammatory lesions of SS patients. Recent studies suggest that serum CXCL13 levels associate with disease severity and risk for non-Hodgkin’s lymphoma (NHL) development. Objectives: To validate the clinical utility of CXCL13 by investigating potential associations of saliva and serum CXCL13 levels with various histopathologic (including severity of MSG autoimmune infiltrates and GC formation), serologic and clinical features of the disease, as well as NHL. Methods: CXCL13 levels were measured by a commercially available ELISA (sensitivity: 1 pg/ml; Abcam, Cambridge, UK) in paired serum and saliva specimens from 25 SS patients (9 with NHL; SSL), 9 sicca controls (SC; sicca-complaining individuals with no infiltrates in diagnostic MSG biopsy and negative autoantibody profile) and 6 healthy controls (HC). From the 16 SS patients without evidence of NHL, 5 had mild, 6 intermediate and 5 severe lesions at MSGs, as arbitrarily defined by focus (FS) and Tarpley (TS) biopsy scores (mild: FS:1-1.7, TS:1, intermediate: FS:1.8-2.95, TS:2 and severe: FS: 3.0-11, TS: 3-4). Furthermore, the organization of the MSG infiltrates to GCs has been evaluated in 23 patients revealing 10 with GCs. Results: Kruskal-Wallis analysis revealed that serum CXCL13 levels were significantly increased in SS patients without or with NHL (median: 94.83 pg/ml and 96.70 pg/ml, respectively), compared to SC and HC (35.44 and 40.92 pg/ml respectively; p&lt;0.05), whereas saliva levels were only marginally increased (76.47, 84.10, 55.98 and 65.30 pg/ml in SS, SSL, SC and HC, respectively, p=0.051). Among SS patients with distinct MSG lesion severity, only those with severe lesions were found to express significantly higher serum CXCL13 levels (149.3 pg/ml) from SC and HC (p: 0,0051 and 0.0166, respectively). Spearman’s Rank correlation analysis showed that both serum and saliva levels correlated with SG biopsy focus score (r: 0.6889, p=0.0001 and r: 0.4222, p=0.01, respectively). Mann-Whitney test revealed that serum CXCL13 levels were significantly elevated in patients with GCs at MSG lesions (156.1 vs 69.64 pg/ml, p:0.0015), rheumatoid factor (105.0 vs 53.72 pg/ml, p: 0.015) and marginally with anti-Ro/La antibodies (121.8 vs 65.05 pg/ml, p: 0.06) compared to those without. Furthermore, CXCL13 levels were significantly increased in SS patients at high risk to develop NHL compared to low risk (149.3 vs 71.54 pg/ml, respectively, p: 0.0275). Saliva levels were not found to associate with the studied features. Conclusion: Serum and to a lesser extend saliva CXCL13 levels are increased in SS and SSL patients and associate with the degree of MSG infiltration, as assessed by focus score. Serum, but not saliva, CXCL13 associates with various disease features, including GC formation, and may have a clinical utility in identifying SS patients at high risk to develop lymphoma. Disclosure of Interests: None declared