Background The proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) are associated with primary Sjögren's syndrome (pSS), because they affect B-cell activity – possible key factor in the pSS pathogenesis.
Objectives The study aimed at determining the correlation between serum concentrations of APRIL /BAFF and markers of pSS and of systemic inflammation.
Methods We evaluated 3 groups: (i) 41 patients with established pSS diagnosis (according to AECG criteria and ACR criteria 2012); [the mean age 51±15.3; 82,9% female (F), 17.1% males (M)]; (ii) 32 subjects with symptoms of dryness (other connective tissue diseases were excluded)[the mean age 56±12,46; (93,75%) F, 2 (6,25%) M], and (iii) 24 healthy volunteers [the mean age 43±12,4; 19 (79,2%), F and 5 (20,8%)M]. Laboratory tests were performed, including establishing inflammatory parameters: erythrocyte sedimentation rate (ESR), serum concentration of C-reactive protein (CRP) (range 0–10 mg/l), concentrations of gamma globulins (g/dl). ANAs titers and patterns were determined by an indirect immunofluorescence method with HEp2 slides. Anti-SSA and anti-SSB antibodies were detected by a dot-blot method allowing semi-quantitative evaluation. Serum concentration of APRIL and BAFF were measured using an enzyme-linked immunosorbent assay. Minor salivary gland biopsies evaluating the number of inflammatory infiltrates foci [focus score (FS) of mononuclear cells above 50] were performed. The study was approved by the Ethics Committee of NIGRR. Differences between groups were analyzed using U Mann-Whitney test (continuous variables). Correlations between variables were assessed with the Spearman correlation coefficient. Statistical significance was set at p<0.05
Results pSS patients had significantly higher serum concentrations of BAFF and ANAs (Mann Whitney test p<0,015, p<0,000 respectively), but not of APRIL, compared to the healthy control (HC) group. There were no differences in serum concentration of BAFF and APRIL between pSS and sicca (S) group. Positive correlation between BAFF and APRIL serum concentrations was found in HC group (r=0,469;p<0,05), but not in pSS and S groups. In S group BAFF positively correlated with CRP (r=0,446;p<0,05) and ANAs positively correlated with a presence of anti-SS-A, anti- SS-B antibodies and a level of gamma globulins. In pSS group there was a statistically significant positive correlation between the concentration of APRIL and: (i) ANAs (r=0,569), (ii) anti-SS-A (r=0,313), (iii) anti -SS-B (r=0,424) and (iv) gamma globulins level (r=0,408). In pSS group ANAs positively correlated with FS (r=0,455).
Conclusions 1. BAFF correlates more closely with an inflammatory reaction, while APRIL with a prolonged autoimmune response, that favoures the production of autoantibodies. 2. Lack of statistically significant differences in the concentrations of BAFF and APRIL between pSS and S group may be explained, based on other studies, by a local BAFF overexpression in salivary glands in pSS group or by an influence of EBV infection or reactivation in both groups (data not shown). 3. Positive correlation between FS and ANAs may suggest a role of ANAs in a local inflammation.
Acknowledgement Financing of the work – research grant NCN 2012/05/N/NZ5/02838.
Disclosure of Interest None declared