Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sjögren's syndrome
| Autor: | Frederik Spijkervet, Jiska Meijer, J. Pijpe, Arjan Vissink, Cornelis Kallenberg, Hendrika Bootsma, Stephan Ihrler, J.E. van der Wal |
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| Rok vydání: | 2009 |
| Předmět: |
CD20
medicine.medical_specialty Pathology Salivary gland medicine.diagnostic_test biology business.industry Immunology medicine.disease Sialadenitis Lymphocytic Infiltrate medicine.anatomical_structure stomatognathic system Rheumatology Biopsy Parenchyma medicine biology.protein Immunology and Allergy Pharmacology (medical) Histopathology Rituximab business medicine.drug |
| Zdroj: | Arthritis & Rheumatism. 60:3251-3256 |
| ISSN: | 0004-3591 |
| DOI: | 10.1002/art.24903 |
| Popis: | Objective To assess the effect of rituximab (anti-CD20 antibody) therapy on the (immuno)histopathology of parotid tissue in patients with primary Sjogren'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/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 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. 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. |
| Databáze: | OpenAIRE |
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