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

Abstract

Objectives: The aim of this study was to assess the histopathological changes in parotid gland tissue of primary Sjögren's syndrome (pSS) patients treated with abatacept.

Methods: In all 15 pSS patients included in the open-label Active Sjögren 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 clini- cal responsiveness as assessed with EULAR Sjögren's syndrome disease activity index (ESSDAI).

Results: Abatacept treatment resulted in a decrease of germinal centres (GCs)/ mm2 (p=0.173). Number of GCs/mm2 at baseline was associated with response in the glandular domain of ESSDAI (Spearman ρ=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/mm2 increased (p=0.041), while numbers of IgA and IgG plasma cells/mm2 were unaffected during abatacept treatment.

Conclusions: 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.