The Open Rheumatology Journal




ISSN: 1874-3129 ― Volume 13, 2019

Resistance to Rituximab Therapy and Local BAFF Overexpression in Sjögren’s Syndrome-Related Myoepithelial Sialadenitis and Low-Grade Parotid B-Cell Lymphoma



Luca Quartuccio1, Martina Fabris1, Massimo Moretti2, Francesca Barone3, Michele Bombardieri3, 4, Maurizio Rupolo5, Sandra Lombardi1, Costantino Pitzalis4, Carlo Alberto Beltrami6, Francesco Curcio2, Salvatore De Vita*, 1
1 Clinic of Rheumatology, DPMSC, University of Udine, Italy
2 Division of General Pathology, DPMSC, University of Udine, Udine, Italy
3 Divisione di Reumatologia, Dipartimento di Clinica e Terapia Applicata, Università La Sapienza, Rome, Italy
4 Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, St. Bartholomew's and Royal London School of Medicine, London, UK
5 Department of Oncology, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano (PN), Italy
6 Department of Pathology, 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.



Article Information


Identifiers and Pagination:

Year: 2008
Volume: 2
First Page: 38
Last Page: 43
Publisher Id: TORJ-2-38
DOI: 10.2174/1874312900802010038

Article History:

Received Date: 22/1/2008
Revision Received Date: 28/1/2008
Acceptance Date: 28/4/2008
Electronic publication date: 28/5/2008
Collection year: 2008

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© Quartuccio et al; Licensee Bentham Open.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.


* Address correspondence to this author at the Ospedale Università Udine, DPMSC, University of Udine, P.z.le S. Maria della Misericordia 1, 33100 Udine, Italy; Tel: 0039.0432.559800; Fax: 0039.0432.559472; E-mail: devita.salvatore@aoud.sanita.fvg.it


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