title: Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sjögren's syndrome.
abstract: OBJECTIVE
  To assess the effect of rituximab (anti-CD20 antibody) therapy on the (immuno)histopathology of parotid tissue in patients with primary Sjögren's syndrome (SS) and the correlation of histologic findings with the flow rate and composition of parotid saliva.
  
  
  METHODS
  In a phase II study, an incisional parotid biopsy specimen was obtained from 5 patients with primary SS before and 12 weeks after rituximab treatment (4 infusions of 375 mg/m(2)). The relative amount of parotid parenchyma, lymphocytic infiltrate, and fat, and the presence/quantity of germinal centers and lymphoepithelial duct lesions were evaluated. Immunohistochemical characterization was performed to analyze the B:T cell ratio of the lymphocytic infiltrate (CD20, CD79a, CD3) and cellular proliferation in the acinar parenchyma (by double immunohistologic labeling for cytokeratin 14 and Ki-67). Histologic data were assessed for correlations with the parotid flow rate and saliva composition.
  
  
  RESULTS
  Four patients showed an increased salivary flow rate and normalization of the initially increased salivary sodium concentration. Following rituximab treatment, the lymphocytic infiltrate was reduced, with a decreased B:T cell ratio and (partial) disappearance of germinal centers. The amount and extent of lymphoepithelial lesions decreased in 3 patients and was completely absent in 2 patients. The initially increased proliferation of acinar parenchyma in response to inflammation was reduced in all patients.
  
  
  CONCLUSIONS
  Sequential parotid biopsy specimens obtained from patients with primary SS before and after rituximab treatment demonstrated histopathologic evidence of reduced glandular inflammation and redifferentiation of lymphoepithelial duct lesions to regular striated ducts as a putative morphologic correlate of increased parotid flow and normalization of the salivary sodium content. These histopathologic findings in a few patients underline the efficacy of B cell depletion and indicate the potential for glandular restoration in SS.
authors.affiliation: University of Groningen, Groningen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Pijpe
authors.forename: J M
authors.initials: JM
authors.lastname: Meijer
authors.forename: H
authors.initials: H
authors.lastname: Bootsma
authors.forename: J E
authors.initials: JE
authors.lastname: van der Wal
authors.forename: F K L
authors.initials: FK
authors.lastname: Spijkervet
authors.forename: C G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: A
authors.initials: A
authors.lastname: Vissink
authors.forename: S
authors.initials: S
authors.lastname: Ihrler
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001706:Biopsy; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008875:Middle Aged; D010306:Parotid Gland / Q000187:drug effects / Q000473:pathology; D000069283:Rituximab; D012463:Saliva; D012469:Salivary Glands / Q000187:drug effects / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab