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Open Rheumatol J. 2008;2:38-43. doi: 10.2174/1874312900802010038. Epub 2008 May 28.

Resistance to rituximab therapy and local BAFF overexpression in Sjögren's syndrome-related myoepithelial sialadenitis and low-grade parotid B-cell lymphoma.

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  • 1Clinic of Rheumatology, DPMSC, University of Udine, Italy.

Abstract

OBJECTIVE:

B-cell expansion is a key feature of Sjögren's syndrome (SS). Accordingly, several studies have reported the benefits of B-cell depletion with anti-CD20 monoclonal antibody (Rituximab) in the treatment of glandular and extraglandular manifestations of SS. Patients with SS are at increased risk of lymphoma development. B-lymphocyte stimulator (BAFF) is an essential cytokine for the control of B-cell maturation and survival, and high levels of BAFF were described in the serum and salivary glands of SS patients, strongly suggesting a crucial role in the proliferation of B cells in SS.

PATIENT AND METHODS:

We describe the treatments employed, with particular regards to rituximab therapy, and the histopathologic and biologic studies, in particular BAFF levels in serum and in pathologic tissues before and after B-cell depletion therapy, and the characterization of the cultured epithelial cells obtained by the parotid gland MALT-lymphoma, in a case of a 51-year old woman with primary SS and mixed cryoglobulinaemia type II with features of systemic vasculitis, who developed a bilateral parotid MALT-type lymphoma. Rheumatoid factor (RF), cryoglobulins, BAFF levels were assessed monthly up to month +6, then at the end of follow-up (month +12), as well as peripheral blood CD19-positive B-cell level

RESULTS:

A significant systemic effect of rituximab on B-cell biomarkers was documented, however, the cryoglobulinemic syndrome did not improve and the parotid enlargement did not decrease confirming the failure of B-cell depletion to affect the parotid lymphoma. BAFF levels decreased only under B-cell depletion associated with high-dose steroids. Tissue studies further documented the persistent overexpression of BAFF in the salivary gland pathologic tissue during the disease course.

CONCLUSION:

Tissue and systemic overexpression of BAFF may have contributed to resistance to rituximab therapy, in MALT lymphoproliferation associated with SS. Thus, alternative treatment strategies should be then considered, possibly including BAFF-targeted approaches.

PMID:
19088870
[PubMed]
PMCID:
PMC2577948
Free PMC Article

Images from this publication.See all images (3)Free text

Fig. (1). Serological changes of rheumatoid factor (RF), cryoglobulins (cryos), BLyS levels and dose changes of daily methylprednisolone (MP) during rituximab (RTX) 650 mg weekly for 8 weeks) infusions and in the subsequent follow-up.
Fig. (2). BAFF and BAFF-R expression in parotid gland (MESA pre-rituximab in the Panel A and C, and MALT NHL postrituximab in the Panel B and D) during the follow-up.
Fig. (3). BAFF expression and secretion modulation by IFN-g stimulation on cultured epithelial cells. (A)
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