P055 CXCL13 as biomarker for histological involvement in sjogren’s syndrome

• Published in: Annals of the rheumatic diseases Vol. 78; no. Suppl 1; p. A24
• Main Authors: Colafrancesco, S, Priori, R, Smith, C, Minniti, A, Iannizzotto, V, Pipi, E, Nayar, S, Campos, J, Lucchesi, D, Arienzo, F, Cerbelli, B, Giordano, C, Valesini, G, Bombardieri, M, Fisher, BA, Barone, F
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 01.03.2019
• Subjects: Animal models; Autoantibodies; Autoimmune diseases; Biomarkers; Biopsy; Cell activation; Chemokines; CXCL13 protein; Gene expression; Germinal centers; Lymphocytes B; Paraffin; Plasma levels; Rheumatoid factor; Ro(SSA) antigen; Salivary gland; Serum levels; Sjogren's syndrome
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2018-EWRR2019.47

Career situation of first and presenting authorPost-doctoral fellow.IntroductionSjogren’s syndrome (SS) is an autoimmune condition characterised by systemic B cell activation, autoantibody production and ectopic germinal centers (GC) formation within salivary gland (SG). The extent of SG infiltrate has been proposed as biomarker of disease severity. Plasma levels of CXCL13 correlate with GC activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B cell activation.ObjectivesTo evaluate the potential role of CXCL13 as biomarker of SG pathology in two independent SS cohorts.Methods109 patients with SS were recruited at Sapienza University of Rome (Italy) (n=60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n=49). Both sera and matched paraffin-embedded minor SG biopsy were available. Sicca (n=57) and healthy subjects (HS) (n=19) sera were used as control. CXCL13 gene expression was also assessed in 25 frozen SGs.ResultsCXCL13 serum levels were higher in SS patients [90.3 (84.2) pg/ml], compared to both sicca [61.9 (38.6) pg/ml), p=0.0005] and HS [36.5 (40.18) pg/ml, p<0.0001]. No differences in average CXCL13 levels were detected between the two SS cohorts [83 (95.2) pg/ml and 103 (64.9) pg/ml, respectively]. In both Italian and British cohorts, serum levels of CXCL13 correlated with the percentage of SG infiltration (p=0.0008 and p=0.0004, respectively), FS (p=0.0010 and p=0.0103, respectively) and mean foci area (p=0.0167 and p=0.0054, respectively); higher serum levels were observed in patients with segregated foci (p=0.0553 and p=0.0019, respectively) and GCs (p=0.0147 and p=0.0044, respectively). Higher CXCL13 serum levels were also associated with anti-Ro/SSA antibodies (p=0.0007, Italian cohort and p=0.0294, British cohort) as well as rheumatoid factor (RF) (p=0.0037, Italian Cohort and p=0.0033, British Cohort). Tissue expression of CXCL13 was moderately correlate with the mean foci area and percentage of infiltration. Higher expression of CXCL13 transcripts was observed in SGs with segregated foci (p=0.0057) and GCs (p=0.0162). Serum levels of CXCL13 did not correlate with local mRNA levels of the same cytokine.ConclusionsOur data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies. Both serum and tissue expression of CXCL13 correlate with SS histological severity, suggesting a major role of this chemokine in SG lymphocytes recruitment and organization.Disclosure of InterestNone declared.