Subgroups of Sj?gren’s syndrome patients categorised by serological profiles: clinical and immunological characteristics

摘要

Objectives Sj?gren’s syndrome (SS) is an autoimmune disease characterised by heterogeneous clinical presentation and presence of various autoantibodies – anti-SSA/Ro of diagnostic value, less specific anti-SSB/La and others. We searched for biomarker(s) and potential therapeutic target(s) of SS subsets that vary in their autoantibody profile. Material and methods Eighty-one patients with SS (70 female and 11 male) and 38 healthy volunteers (28 female and 10 male) were included in the study. Patients were categorised according to absence (group 1) or presence of anti-SSA/Ro antibody which occurred either alone (group 2) or together with anti-SSB/La (group 3). Clinical evaluation was performed, and presence of autoantibodies and concentrations of cytokines relevant to SS pathogenesis, i.e. a proliferation inducing ligand (APRIL), B-lymphocyte activating factor (BAFF), interleukin (IL) 4, IL-10, interferon ? (IFN-?) and thymic stromal lymphopoietin (TSLP), in sera were determined. Results Frequency of autoantibodies other than anti-SSA/Ro and anti-SSB/La, the number of autoantibody specificities and anti-nuclear antibody titres were higher in group 2 and/or 3 than in group 1 of SS patients. Moreover, SS patients of groups 2 and 3 developed disease symptoms at younger age, and more often had positive Schirmer’s test and skin lesions. In addition, serum concentrations of APRIL, but not other tested cytokines, were significantly higher in the patients of both groups 2 and 3 than those of group 1 and healthy volunteers. Conclusions Sj?gren’s syndrome patients with signs of B-cell epitope spreading are characterised by early disease onset, more frequent xerophthalmia and skin involvement, and up-regulated serum APRIL level. We suggest that therapeutic neutralisation of APRIL may be beneficial for these patients.