Cytokine and autoantibody profiling related to histopathological features in primary Sjogren's syndrome.

ABSTRACT

OBJECTIVE: To investigate a potential correlation between circulating cytokine and autoantibody levels and histopathological features in subgroups of patients with primary SS (pSS). METHODS: Minor salivary gland biopsies from a cohort of 141 patients fulfilling the American-European consensus classification criteria for pSS were re-examined and grouped according to focus score (FS) and germinal centre (GC) status; serum samples were analysed for autoantibodies, chemokines and cytokines. RESULTS: Of the 115 available biopsies, 18 (16%) lacked characteristic focal mononuclear cell infiltrates [FS < 1 (FS-)] but patients were positive for Ro/SSA and/or La/SSB. IL-17, IL-1RA, IL-15, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, eotaxin, IFN-alpha and IL-4 levels were significantly increased in the 27 (23%) patients with ectopic GC formation (GC+) in the salivary glands compared with the GC- patients (n = 70). In addition, minor differences in cytokine levels were found when comparing age groups. CONCLUSION: Degenerative changes observed in the minor salivary glands of patients with pSS may represent 'burned out' inflammation. The elevated levels of IL-4 found in these patients may influence the reduced salivary flow observed in GC+ patients. Increased titres of Th17-associated cytokines, IL-17, IL-1beta and the IL-23 subunit IL-12p40, may indicate a higher activity of these cells in GC+ patients. Differences in cytokine levels may be utilized when sub-grouping the SS patients into disease phases and may consequently have implications for treatment.