title: B cells in systemic sclerosis: a possible target for therapy.
abstract: Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive extracellular matrix (ECM) deposition in the skin and other visceral organs and it is associated with immune activation characterized by autoantibody production, release of various cytokines and T-lymphocyte activation. Several recent lines of evidence in animal models and in SSc patients indicate a potential role for B cells in the SSc. B cells have arisen as a possible player in tissue fibrosis in some experimental models and, since IL-6 produced by B cells, along with TGF-β, may induce matrix synthesis and less collagen degradation, targeting B cells could be one way to reduce ECM deposition and reduce the inflammatory background. Both SSc patients and tight-skin mice, a genetic model of SSc, have intrinsic B-cell abnormalities characterized by chronic B-cell activation. SSc patients present an increased number of naïve B cells and an activation of memory B cells, despite a reduction in their number. B cells from SSc patients exhibit increased expression of CD19. Remarkably, CD19 loss or B-cell depletion using antimouse CD20 antibody suppresses the development of skin hyperplasia and autoimmunity in tight-skin mice. Additionally, recent studies revealed a possible beneficial effect of anti-human CD20 antibody (Rituximab) therapy on skin fibrosis and lung involvement in SSc patients. These studies reported also the safety of Rituximab in SSc patients. All these findings suggest a possible role of antiCD20 treatment in SSc patients.
authors.affiliation: Division of Rheumatology, Catholic University, Medical School, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bosello
authors.forename: Giacomo
authors.initials: G
authors.lastname: De Luca
authors.forename: Barbara
authors.initials: B
authors.lastname: Tolusso
authors.forename: Gina
authors.initials: G
authors.lastname: Lama
authors.forename: Cristiana
authors.initials: C
authors.lastname: Angelucci
authors.forename: Gigliola
authors.initials: G
authors.lastname: Sica
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferraccioli
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D005355:Fibrosis; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D051379:Mice; D008817:Mice, Mutant Strains; D058990:Molecular Targeted Therapy; D000069283:Rituximab; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab