Document Detail

Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sj??gren's syndrome.
MedLine Citation:
PMID:  19877054     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To assess the effect of rituximab (anti-CD20 antibody) therapy on the (immuno)histopathology of parotid tissue in patients with primary Sj??gren'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.
J Pijpe; J M Meijer; H Bootsma; J E van der Wal; F K L Spijkervet; C G M Kallenberg; A Vissink; S Ihrler
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  60     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-10     Completed Date:  2010-01-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3251-6     Citation Subset:  AIM; IM    
University of Groningen, Groningen, The Netherlands.
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MeSH Terms
Antibodies, Monoclonal / pharmacology,  therapeutic use*
Antirheumatic Agents / pharmacology,  therapeutic use*
Cell Proliferation
Middle Aged
Parotid Gland / drug effects,  pathology
Salivary Glands / drug effects,  pathology*
Sjogren's Syndrome / drug therapy*,  pathology*
Treatment Outcome
Tumor Necrosis Factor-alpha / antagonists & inhibitors
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antirheumatic Agents; 0/Tumor Necrosis Factor-alpha; 0/rituximab

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