Subgroups of Sjögren's syndrome patients categorised by serological profiles: clinical and immunological characteristics

Abstract

Objectives: Sjögren'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 α (IFN-α) 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: Sjögren'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.

Keywords: APRIL; Sjögren’s syndrome; clinical symptoms; epitope spreading.

Fig. 1

Serological differences between subgroups of Sjögren’s syndrome patients. Data are expressed as the median with interquartile range (IQR) of continuous variables (panels B and D) or as a frequency distribution of discrete variables (panels A and C). Patients were categorised as follows: group 1 – patients negative for anti-SSA/Ro and anti-SSB/La antibodies, group 2 – patients positive for anti-SSA/Ro antibody only, and group 3 – patients seropositive for both anti-SSA/Ro and anti-SSB/La antibodies. The number of patients having autoantibodies other than anti-SSA/Ro and anti-SSB/La (A), number of specificities of autoantibodies (B), number of patients positive for rheumatoid factor (RF) (C) and the titre of antinuclear antibodies (D) are shown in every group. Each point represents one patient (B and D). For statistically significant differences between patient groups p-values are shown: ^*p = 0.05–0.01; ^**p = 0.01–0.001; ***p < 0.0001.

Fig. 2

Demographic differences between subgroups of Sjögren’s syndrome patients. Data are expressed as the median with interquartile range (IQR). Each point represents one patient or healthy volunteer. Patients were categorised as described in Figure 1. For statistically significant differences between patients and healthy control (C) (^## p = 0.01–0.001; ^### p < 0.0001) as well as between patient subgroups (*p = 0.05–0.01; **p = 0.01–0.001) p-values are shown; ns – not significant.

Fig. 3

Clinical differences between subgroups of Sjögren’s syndrome patients. Data are expressed as a frequency distribution of discrete variables. Patients were categorised as described in Figure 1. For statistically significant differences between patient subgroups p-values are shown: *p = 0.05–0.01.

Fig. 4

Serum concentrations of tested cytokines in subgroups of Sjögren’s syndrome patients. Results are expressed as the median (horizontal line) with interquartile range (IQR, box), lower and upper whiskers (data within 3/2xIQR) and outliers (points) (Tukey’s box). Patients were categorised as described in Figure 1. Control – healthy volunteers; APRIL – a proliferation inducing ligand; BAFF – B-lymphocyte activating factor; IL – interleukin; TSLP – thymic stromal lymphopoietin; IFN-α – interferon α. For statistically significant differences between patients and healthy control (^## p = 0.01–0.001; ^### p < 0.0001) as well as between patient subgroups (^* p = 0.05–0.01; ^** p = 0.01–0.001) p-values are shown.