Association between IL-7 and primary Sjogren's syndrome: A single-center study and a systematic scoping review.

BACKGROUND: There is a lack of single marker reflecting systemic activity of primary Sjogren's syndrome (pSS). Our aim is to determine the association between interleukin(IL)-7 and pSS by combining a single-center study and a systematic scoping review. METHODS: There were 58 patients with pSS and 30 healthy controls (HCs) included in the single-center study. The multiplex immunoassay was used for detecting concentrations of IL-7, IL-4, IL-9, IL-10, IL-17, interferon(IFN) -gamma, INF-alpha and INF-beta in sera. pSS patients were evaluated for systemic activity in accordance with the European League against Rheumatism SS Disease Activity Index (ESSDAI). In the systematic scoping review, all studies regarding association of IL-7 with pSS were included. RESULTS: pSS patients showed higher serum IL-7 levels (P = 0.028 vs HCs) which were associated with neutrophil, neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphacyte ratio(PLR), red blood cell distribution width(RDW), erythrocyte sedimentation rate(ESR), immunoglobulin(Ig)G, C-reactive protein (CRP), fever, lymphadenopathy and ESSDAI. Serum IL-7 correlated with Th cell related cytokines. Findings of the systematic scoping review on 15 articles were as follows. Firstly, IL-7 expression in salivary glands (SGs), serum and saliva increased in pSS, while IL-7 receptor(IL-7R) expression increased in SGs but decreased in peripheral blood. Secondly, increased IL-7 was mainly from SGs of pSS patients, but whether IL-7 was mainly produced by SG epithelial cells remained to be validated. Thirdly, IL-7 could exert a key role in pSS immunopathology. Although IL-7 had no direct effect on SGECs, it could activate B and T cells and stimulate secretion of IL-17, IL-4 and IFNs. CONCLUSION: Not only are IL-7 and soluble IL-7R potential biomarkers for monitoring pSS activity, but also targeting IL-7/IL-7R pathway may be a promising therapeutic strategy.