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Clin Exp Rheumatol. 2015 Jul-Aug;33(4 Suppl 91):S160-7. Epub 2015 Sep 1.

Reduced type I collagen gene expression by skin fibroblasts of patients with systemic sclerosis after one treatment course with rituximab.

Author information

1
Clinica Medica, Dipartimento di Medicina Interna, Ospedali Riuniti, Ancona, Italy.
2
Clinica di Reumatologia, Dipartimento di Patologia e Medicina Sperimentale e Clinica, Università di Udine, Udine, Italy.
3
Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
4
Istituto di Anatomia Patologica, Dipartimento di Ricerche Mediche e Morfologiche Università di Udine, Udine, Italy.
5
Clinica Medica, Dipartimento di Medicina Interna, Ospedali Riuniti, Ancona; and Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
6
Clinica Medica, Dipartimento di Medicina Interna, Ospedali Riuniti, Ancona; and Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy. a.gabrielli@univpm.it.

Abstract

OBJECTIVES:

There is evidence that B lymphocytes play a role in the pathogenesis of systemic sclerosis (scleroderma). Stimulatory autoantibodies targeting and activating normal human fibroblasts in vitro have been demonstrated in sera from scleroderma patients. Rituximab is a monoclonal antibody which selectively targets and depletes CD20+ B lymphocytes. We investigated the biological effects of rituximab in six patients affected by scleroderma with severe skin involvement.

METHODS:

Six patients with severe skin fibrosis, unresponsive to immunosuppressive treatment, were treated with 375 mg/m2 per week of intravenous rituximab for a total of four doses. Serum stimulatory autoantibodies to the PDGF receptor were detected. Fibroblast activation was evaluated in fibroblasts grown from skin biopsies performed at baseline and at months 3 and 6 post-treatment. The modified Rodnan's skin score, health assessment questionnaire (HAQ) and visual analogic scale (VAS) for global wellness and B lymphocyte count were performed monthly.

RESULTS:

A significant reduction of anti-PDGF receptor autoantibodies was observed in the serum of all patients 3 months after treatment. Fibroblasts showed a significant downregulation of type I collagen gene expression and of the intracellular signalling triggered by anti-PDGFR autoantibodies. A decrease of the skin score and an improvement of disability indexes matched with the in vitro results. A single course of rituximab reduced scleroderma fibroblast activation in vitro and the serum levels of anti-PDGFR stimulatory autoantibodies.

CONCLUSIONS:

These data provide further evidence of B-cell involvement in the pathogenesis of scleroderma. Targeting B cells may be a promising treatment for scleroderma patients, and controlled clinical trials are warranted.

PMID:
26339895
[Indexed for MEDLINE]

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