Abatacept treatment of patients with primary Sjögren's syndrome results in a decrease of germinal centres in salivary gland tissue

Objective. The aim of this study was to assess the histopathological changes in parotid gland tissue of primary Sjogren's syndrome (pSS) patients treated with abatacept.Methods. In all 15 pSS patients included in the open-label Active Sjogren Abatacept Pilot (ASAP, 8 abatacept infusions) study parotid gland biopsies were taken before treatment and at 24 weeks of follow up. Biopsies were analysed for pSS-related histopathological features and placed in context of clinical responsiveness as assessed with EULAR Sjogren's syndrome disease activity index (ESSDAI).Results. Abatacept treatment resulted in a decrease of germinal centres (GCs)/mm(2) (p=0.173). Number of GCs/mm(2) at baseline was associated with response in the glandular domain of ESSDAI (Spearman.=0.644, p=0.009). Abatacept treatment did not reduce focus score, lymphoepithelial lesions, area of lymphocytic infiltrate, amount of CD21(+) networks of follicular dendritic cells, and numbers of CD3(+) T-cells or CD20(+) B-cells. Number of IgM plasma cells/mm(2) increased (p=0.041), while numbers of IgA and IgG plasma cells/mm(2) were unaffected during abatacept treatment.Conclusion. Abatacept affects formation of GCs of pSS patients in parotid glands, which is dependent on co-stimulation of activated follicular-helper-T-cells. Herewith, local formation of (autoreactive) memory B-cells is inhibited. Presence of GCs at baseline predicts responsiveness to abatacept in the ESSDAI glandular domain.