The effect of rituximab on encapsulated peritoneal sclerosis in an experimental rat model

Abstract

Introduction Peritoneal sclerosis may be observed in varied manifestations. However, the most serious form is encapsulated peritoneal sclerosis (EPS). EPS has a low prevalence of up to 3%, but it is associated with a high mortality rate of up to 51% in patients undergoing peritoneal dialysis (PD). Therefore, EPS is of major concern to nephrologists []. The characteristic feature of EPS is extreme sclerosis of the peritoneal membrane, which covers and constricts the intestines []. Although several studies have examined EPS, the exact pathophysiology of EPS remains unclear. The triggering factors involved in the pathogenesis of systemic fibrosis and EPS were M2type macrophages, CD4+T cells [], B cells [], the matrix metalloproteinase (MMP) family, particularly MMP-2 [,], and transforming growth factor-beta 1 (TGF-β1) []. Nishino et al. reported that T and B lymphocytes had important roles in the process of peritoneal fibrosis in a mouse peritoneal fibrosis model []. However, Habib et al. reported that there were no CD20 and CD15 positive cells in the biopsies of a subgroup of patients with EPS []. Conversely, Bosello reported the potential role of B cells in tissue fibrosis in some experimental models, thus, targeting B cells could be one method of reducing extracellular matrix deposition and lowering the inflammatory status [4]. Research has also shown the effect of the anti-B cell monoclonal antibody, rituximab, in the treatment of diseases involving fibrotic processes [4,,]. A variety of therapeutic approaches to EPS including surgical and medical options have been reported []. In recent studies, the effects of various immunosuppressive drugs such as prednisone, azathioprine, mycophenolate mofetil (MMF), and sirolimus have been investigated [,]. We reported the effect of the T cell blocker abatacept in the treatment of EPS in our previous study []. However, to our knowledge, no data on the effect of the anti-CD 20 + antibody, rituximab, in EPS models are available. Rituximab (MabThera/Rituxan), a chimeric murine/ human monoclonal antibody, binds specifically to the transmembrane antigen CD20 on B cells []. The aim of this study was to investigate the effect of rituximab in an experimental rat model in which Background/aim: Peritoneal sclerosis may be observed in varied manifestations. However, the most serious form is the encapsulated peritoneal sclerosis. We researched the effect of rituximab on peritoneal fibrosis in an experimental rat model. Materials and methods: Twenty-four Wistar Albino rats were divided into 4 equal groups. During weeks 0-3; group I received isotonic saline (IS) solution, group II, group III, and group IV received chlorhexidine gluconate (CG) via intraperitoneal (i.p.) route. In the next 3 weeks nothing adminestred to both group I and group II but IS solution was adminestred to group III via i.p. route and 375 mg/m2/ week rituximab was applied intravenously on days 21, 28, and 35 to group IV. Fibrosis, peritoneal thickness, and inflammation were evaluated. Immunohistochemical methods use...