S-160 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. *These authors contributed equally to this work. Paolo Fraticelli, MD Salvatore De Vita, MD Nicoletta Franzolini, MD Silvia Svegliati, PhD Caterina A. Scott, MD Cecilia Tonnini, PhD Tatiana Spadoni, PhD Barbara Gabrielli, MD Giovanni Pomponio, MD Gianluca Moroncini, MD, PhD Armando Gabrielli, MD Please address correspondence to: Dr Armando Gabrielli, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Via Tronto 10, 60020 Ancona, Italy. E-mail: a.gabrielli@univpm.it Received on June 9, 2015; accepted in revised form on July 1, 2015. Clin Exp Rheumatol 2015; 33 (Suppl. 91): S160-S167. © Copyright CliniCal and ExpErimEntal rhEumatology 2015. Key words: systemic sclerosis, B cells, autoimmune disease Funding: this work was supported in part by the Società Italiana di Reumatologia, Associazione Italiana per la Lotta alla Sclerodermia, Ministero Italiano per l’Università e la Ricerca Scientiica and by a special grant from the Fondazione Cariverona e Fondazione di Medicina Molecolare e Terapia Cellulare, Ancona, Italy. Competing interests: none declared. ABSTRACT Objective. There is evidence that B lymphocytes play a role in the patho- genesis of systemic sclerosis (scleroder- ma). Stimulatory autoantibodies target- ing and activating normal human ibro- blasts 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 ibrosis, unresponsive to immunosup- pressive treatment, were treated with 375 mg/m 2 per week of intravenous rituximab for a total of four doses. Se- rum stimulatory autoantibodies to the PDGF receptor were detected. Fibro- blast activation was evaluated in ibro- blasts grown from skin biopsies per- formed at baseline and at months 3 and 6 post-treatment. The modiied Rodnan’s skin score, health assessment question- naire (HAQ) and visual analogic scale (VAS) for global wellness and B lym- phocyte count were performed monthly. Results. A signiicant reduction of an- ti-PDGF receptor autoantibodies was observed in the serum of all patients 3 months after treatment. Fibroblasts showed a signiicant downregulation of type I collagen gene expression and of the intracellular signalling trig- gered by anti-PDGFR autoantibod- ies. A decrease of the skin score and an improvement of disability indexes matched with the in vitro results. A sin- gle course of rituximab reduced scle- roderma ibroblast activation in vitro and the serum levels of anti-PDGFR stimulatory autoantibodies. Conclusion. These data provide fur- ther 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. Introduction Systemic sclerosis (SSc) is a connec- tive tissue disease characterised by increased production of extracellular matrix by ibroblasts, both in the skin and in visceral organs. The aetiology is unknown, and key pathogenetic events include immune system activation, en- dothelial cell dysfunction and ibroblast activation (1-3). Although current therapies can control end organ damage (4), no disease-mod- ifying agent able to induce complete re- mission of the disease is available yet, probably due to the poor knowledge of the mechanisms implicated in the pathophysiology of the disease (5). It has been shown that SSc patients are characterised by activation of humoral immunity. Whitield et al. using DNA microarrays have revealed up-regula- tion of genes related to B cells in SSc skin lesions (6). Furthermore, memory B cells have been found to be activated in scleroderma patients and showed enhanced ability to produce IgG in vitro under well deined experimental conditions (7). Increased serum levels of BAFF or B cell-activating factor, a potent B cell survival factor, were detected in an unselected SSc popula- tion and found to correlate positively with the extent of skin ibrosis (8). The activation of B cells may lead to in- creased production of IL-6 and TGF-β which induce ibrosis (9) and IL-10 and IL-6 which drive a Th2-dominant im- mune response (10, 11) involved in the mechanisms of autoantibody produc- tion (12). The description of several autoantibodies directed against non-nu- Reduced type I collagen gene expression by skin ibroblasts of patients with systemic sclerosis after one treatment course with rituximab P. Fraticelli 1 , S. De Vita 2 , N. Franzolini 2 , S. Svegliati 3 , C.A. Scott 4 , C. Tonnini 3 , T. Spadoni 3 , B. Gabrielli 3 , G. Pomponio 1 , G. Moroncini 1,3 , A. Gabrielli 1,3