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

✍ Scribed by J. Pijpe; J. M. Meijer; H. Bootsma; J. E. van der Wal; F. K. L. Spijkervet; C. G. M. Kallenberg; A. Vissink; S. Ihrler


Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
236 KB
Volume
60
Category
Article
ISSN
0004-3591

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✦ Synopsis


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.

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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## Objective: In patients with sjögren's syndrome (ss), b lymphocytes have been found to infiltrate salivary glands, resulting in sialadenitis and keratoconjunctivitis. the disease is frequently associated with benign and neoplastic lymphoproliferation. the present study was undertaken to investiga