Autoantibody levels correlate with CXCL13 in human Sjogrens Syndrome

Sjogrens Syndrome (SS) is a debilitating immune dyscrasia that may have severe oral manifestations. Primary SS (pSS) patients typically exhibit xerostomia and xerophthalmia, while those with secondary SS (sSS) have an additional autoimmune disease. Many autoimmune diseases demonstrate B cell hyperactivity that may initiate and/or exacerbate disease, and this paradigm extends to SS as well. Objectives: We hypothesize that the B cell chemokine, CXCL13, is elevated in SS patients. Moreover, we postulate that levels of CXCL13 correlate with autoantibody titers in these individuals. Methods: To extend our previous findings, we used ELISAs to quantify CXCL13 in sera and saliva of SS patients. Furthermore, we measured serum autoantibody levels by ELISA. Statistical analyses were carried out using the Mann-Whitney test and Spearman correlation coefficient. Results: Patients with pSS (n=28) have high serum CXCL13 compared to healthy controls (n=12) (p=0.0007). Since elevated CXCL13 is documented in other primary autoimmune diseases, we did not test sera of patients with sSS. However, patients with pSS and sSS have elevated CXCL13 in saliva (n=29) (p=0.0167) as compared to normal controls. Salivary CXCL13 levels are elevated in SS patients with xerostomia (n=14) as compared to SS patients with normal salivary flow (n=15) (p=0.022), while serum CXCL13 is similar between the two groups. In patients with pSS, serum CXCL13 levels correlate with anti-SSA titers (p=0.016). Moreover, anti-SSB values correlate with salivary CXCL13 levels in both pSS and sSS (p=0.019). Conclusion: CXCL13 is a novel biomarker in SS disease, although studies with more individuals are needed to establish the level of serum CXCL13 indicative of disease. Furthermore, salivary CXCL13 may identify a subset of SS patients with particularly severe oral disease. Accordingly, CXCL13 levels correlate with SS autoantibodies in sera and saliva, indicating that CXCL13 may be a local and systemic marker of B cell dysfunction in SS.