Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sjögren's syndrome

J Pijpe, JM Meijer, H Bootsma… - … : Official Journal of …, 2009 - Wiley Online Library
J Pijpe, JM Meijer, H Bootsma, JE van der Wal, FKL Spijkervet, CGM Kallenberg, A Vissink…
Arthritis & Rheumatism: Official Journal of the American College …, 2009Wiley Online Library
Methods. In a phase II study, an incisional pa-rotid biopsy specimen was obtained from 5
patients with primary SS before and 12 weeks after rituximab treatment (4 infusions of 375
mg/m2). 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 …
Methods. In a phase II study, an incisional pa-rotid biopsy specimen was obtained from 5 patients with primary SS before and 12 weeks after rituximab treatment (4 infusions of 375 mg/m2). 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 sali-vary 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.
Conclusion. 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.
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