title: Abatacept treatment of patients with primary Sjögren's syndrome results in a decrease of germinal centres in salivary gland tissue.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Rheumatology and Clinical Immunology, and Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Erlin A
authors.initials: EA
authors.lastname: Haacke
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: van der Vegt
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Petra M
authors.initials: PM
authors.lastname: Meiners
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Vissink
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Fred K L
authors.initials: FK
authors.lastname: Spijkervet
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Hendrika
authors.initials: H
authors.lastname: Bootsma
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Frans G M
authors.initials: FG
authors.lastname: Kroese
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001706:Biopsy; D018858:Germinal Center / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D010306:Parotid Gland / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000069594:Abatacept