RESEARCH - Evidence of salivary gland restoration supports the efficacy of rituximab in Sjogren's syndrome

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Arthritis Rheum. 2009 Nov;60(11):3251-6.

Clinical and histologic evidence of salivary gland restoration

supports the efficacy of rituximab treatment in Sjögren's syndrome.

Pijpe J, Meijer JM, Bootsma H, van der Wal JE, Spijkervet FK,

Kallenberg CG, Vissink A, Ihrler S.

University of Groningen, Groningen, The Netherlands.

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.

PMID: 19877054

http://www.ncbi.nlm.nih.gov/pubmed/19877054

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