ASSOCIATION OF SERUM INTERFERON-INDUCIBLE CHEMOKINES WITH SYSTEMIC DISEASE ACTIVITY, BAFF AND MARKERS OF B-CELL ACTIVATION IN PATIENTS WITH PRIMARY SJÖGREN'S SYNDROME

Background: In primary Sjögren's syndrome (pSS), the activation of interferon (IFN) pathways was demonstrated in PBMCs and salivary glands. Levels of 3 IFN-inducible chemokines, CXCL10 (IP-10), CCL2 (MCP-1) and CCL19 (MIP-3β) were reported to be associated with the interferon signature and disease activity in systemic lupus erythematosus. We therefore investigated the interest of these 3 chemokines as biomarkers in pSS Methods: Serum levels of CXCL10, CCL2, CCL19, BAFF, IgG, free light chains (FLCs) of immunoglobulins (Igs) and beta2-microglobulin were assessed at enrollment in all the patients, using ELISA (CXCL10, CCL19, BAFF) and in 88 healthy blood donors. IRF5 and STAT4 polymorphisms were analyzed: IRF5 rs2280714 and IRF5 rs2004640, IRF5 promoter CGGGG indel and STAT-4 rs75822694. Results: Serum median levels of CXCL10 and CCL19 were higher in patients with pSS than in controls (37.6 vs 15.6 pg/ml and 332.2 vs 92.2 pg/ml, respectively, P<0.0001 for each). Conversely, serum median levels of CCL2 was lower in patients with pSS than in controls (117.5 vs 184.5 pg/ml, P<0.0001). IRF5 and STAT4 at-risk genotypes were associated with increased levels of serum CCL19 (IRF5 rs2280714: T/T median CCL19 of 390.7 pg/ml, T/C: 319.9 pg/ml, C/C: 263.8 pg/ml, P=0.007; IRF5 rs2004640: T/T median CCL19 of 371.2 pg/ml, T/G: 347.1 pg/ml, G/G: 271.1 pg/ml, P=0.01; IRF5 4R carriers: median CCL19 of 383.5 vs 297.1 pg/ml, P=0.008; STAT4: C/C median CCL19 of 537.3 pg/ml; C/G: 390.7 pg/ml, GG: 300.5 pg/ml, P=0.02), but not with serum levels of CCL2 and CXCL10. Patients with increased CXCL10 and CCL19 had a significantly higher systemic disease activity assessed by median ESSDAI (5.5 vs 3.0 and 4.0 vs 3.0, P=0.001 and P=0.03 respectively). Serum levels of CXCL10 (r=0.3, P<0.0001) and of CCL19 (r=0.2, P=0.0003) were significantly correlated with serum BAFF level. Patients with increased CXCL10 and CCL19 had higher median levels of beta2-microglobulin (2.9 vs 1.9 mg/l and 2.5 vs 2.0, respectively, P<0.0001 for each), kappa(21.3 vs 12.5 mg/l and 17.2 vs 12.4 mg/l respectively, P<0.0001 for each) and lambda FLCs (17.2 vs 12.7 mg/L and 17.1 vs 12.3 mg/l, respectively, P<0.0001 for each). Conclusions: Serum levels of CXCL10 and CCL19, 2 IFN-inducible chemokines, are increased in pSS. IRF-5 and STAT-4 at-risk genotypes are associated with CCL19 increase. The increased level of CXCL10 and CCL19 is also associated with disease activity and drives, at least partly, the increase of BAFF and markers of B cell activation in pSS Disclosure of Interest: None DeclaredCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 311Session: SLE, Sjögren's and APS – clinical aspects (other than treatment) (Poster Presentations )