Michiel G H Betjes1, Meelad S Habib1, Dick G Struijk2, Deirisa Lopes Barreto2, Mario R Korte3, Alferso C Abrahams4, Nicole M A Nagtzaam5, Marian C Clahsen-van Groningen6, Willem A Dik5, Nicolle H R Litjens1. 1. Department of Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands. 2. Department of Internal Medicine, Division of Nephrology, Academic Medical Center, Amsterdam, The Netherlands. 3. Department of Internal Medicine, Division of Nephrology, Albert Schweitzer Hospital, Dordrecht, The Netherlands. 4. Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands. 5. Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands. 6. Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
Abstract
BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is an excessive fibrotic response of the peritoneum that may occur after long-term peritoneal dialysis (PD). The underlying pathophysiology is poorly understood, but involvement of peritoneal inflammatory T helper 1 cells may be pivotal. METHODS: Soluble interleukin-2 receptor alpha (sCD25) concentration was measured as a marker for T-cell activation in serum and ascites from EPS patients and various control patient groups. Peritoneal biopsies were stained for the presence of T cells, and T cells isolated from ascites of EPS patients were characterized in detail for differentiation status and cytokine expression. RESULTS: Serum sCD25 concentrations are significantly and specifically increased in EPS patients compared with haemodialysis, PD and predialysis patients. Peritoneal effluent of stable PD patients contains very low levels of sCD25, while sCD25 levels in ascites of EPS patients are high and indicative of local production. In the years preceding the diagnosis of EPS, the serum sCD25 concentrations increased while remaining at stable levels in control PD patients. The peritoneum and ascites of EPS patients showed a significant influx of T cells with relatively increased numbers of CD4(+) T cells. These T cells were fully differentiated and displayed a T helper 1 cell type with a pro-inflammatory cytokine profile. CONCLUSIONS: Increased serum sCD25 concentrations and peritoneal lymphocytosis in EPS patients indicate the involvement of activated T cells in the pathophysiology of excessive fibrosis.
BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is an excessive fibrotic response of the peritoneum that may occur after long-term peritoneal dialysis (PD). The underlying pathophysiology is poorly understood, but involvement of peritoneal inflammatory T helper 1 cells may be pivotal. METHODS: Soluble interleukin-2 receptor alpha (sCD25) concentration was measured as a marker for T-cell activation in serum and ascites from EPSpatients and various control patient groups. Peritoneal biopsies were stained for the presence of T cells, and T cells isolated from ascites of EPSpatients were characterized in detail for differentiation status and cytokine expression. RESULTS: Serum sCD25 concentrations are significantly and specifically increased in EPSpatients compared with haemodialysis, PD and predialysis patients. Peritoneal effluent of stable PDpatients contains very low levels of sCD25, while sCD25 levels in ascites of EPSpatients are high and indicative of local production. In the years preceding the diagnosis of EPS, the serum sCD25 concentrations increased while remaining at stable levels in control PDpatients. The peritoneum and ascites of EPSpatients showed a significant influx of T cells with relatively increased numbers of CD4(+) T cells. These T cells were fully differentiated and displayed a T helper 1 cell type with a pro-inflammatory cytokine profile. CONCLUSIONS: Increased serum sCD25 concentrations and peritoneal lymphocytosis in EPSpatients indicate the involvement of activated T cells in the pathophysiology of excessive fibrosis.
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