Relationships between increased circulating YKL-40, IL-6 and TNF-α levels and phenotypes and disease activity of primary Sjogren's syndrome

Background: There is now no single score or marker useful for evaluating disease activity of primary Sjogren's syndrome (pSS). This study was designed to explore the associations of circulating YKL-40, interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) with systemic activity and phenotypes of pSS. Methods: This study included 58 pSS patients and 30 healthy controls (HC). The sera were measured by multiplex immunoassay for YKL-40, IL-6 and TNF-alpha concentrations. The disease activity of pSS patients was evaluated by European league against rheumatism (EULAR) SS disease activity index (ESSDAI). Local severity was assessed in accordance with the Tarpley score. Results: Serum YKL-40, IL-6 and TNF-alpha levels significantly elevated in pSS patients compared with those in HC (all P < 0.001). These cytokines correlated with ESSDAI, ESR, CRP, and IgG (all P < 0.05). Serum YKL-40 level correlated markedly with age (r = 0.405, P = 0.002), neutrophil count (r = 0.399, P = 0.002) and neutrophil-to-lymphocyte ratio (NLR) (r = 0.401, P = 0.002), while IL-6 did weakly with NLR (r = 0.296, P = 0.024) and C3 (r = 0.288, 0.036). Serum levels of all three cytokines were substantially lower in patients with eye/mouth dryness vs. those without (all P < 0.05). Additionally, patients with pulmonary, renal involvement or anemia had remarkably higher concentrations of YKL-40 (all P < 0.05), while those with leukocytopenia had lower levels (P = 0.01). Fever or anemia patients showed higher serum concentrations of IL-6 (both P < 0.05), while serum levels of TNF-alpha were much higher in patients with presence of ANA, anti-SSA or anti-SSB antibodies (All P < 0.05). Serum IL-6 level correlated strongly with YKL-40 (r = 0.452, P < 0.001) and TNF-alpha (r = 0.743, P < 0.001) in pSS patients. A significant correlation was also found between YKL-40 and TNF-alpha (r = 0.308, P = 0.022). Conclusion: The circulating YKL-40, IL-6 and TNF-alpha levels increase in pSS, and all of them are significantly correlated with indicators (ESSDAI, ESR, CRP, and IgG) for systemic inflammation of pSS. Each cytokine is separately associated with specific pSS phenotype.