Peritoneal Sclerosis in a Patient on Long-term Continuous Ambulatory Peritoneal Dialysis (CAPD). : An Autopsy Case.

若年性ネフロン癆による慢性腎不全でCAPD (continuous ambulatory peritoneal dialysis)導入し, 6年6ヵ月後に死亡した20歳男性の1剖検例を報告した。CAPD導入数カ月後, 腹膜炎による除水能低下を起こしたが, 約5ヵ月後に回復した。CAPD導入1年5ヵ月以降重症な腹膜炎罹患により除水能低下状態が遷延したが, 次第に回復した。しかし, 体液貯留傾向のため, 3年2ヵ月後より高張透析液を使用し除水量の増加を得たが, 3年9ヵ月後に不可逆的な除水能低下状態となった。一方, クレアチニンの透析排液/血漿濃度比(D/P)から見た溶質除去能は, その約半年後まで保たれており, 血清クレアチニン値の上昇は軽度であった。剖検にて腹膜の線維性肥厚と高度の内腔狭窄を伴う動静脈硬化を認め, 腹膜硬化症と診断した。本例の腹膜硬化症は, 頻回の腹膜炎と高張透析液の使用が主な原因と考えられた。腹膜機能を長期に維持するためには, 腹膜炎の予防と高張透析液の使用を最小限にすることが重要と考えられた。A 20-year-old man, treated with continuous ambulatory peritoneal dialysis (CAPD) for 6.5 years because of-end-stage renal disease due to juvenile nephronophthysis, died of ultrafiltration failure, and the morphological examination of peritoneum was carried out at autopsy. Nine episodes of peritonitis developed, and ultrafiltration transiently decreased after each episodes. At 2 years after the start of CAPD, severe peritonitis occurred, and then his body weight and blood pressure gradually increased. At 4 years after the beginning of CAPD, when hyperosmotic dialysate was frequently used, ultrafiltration was irreversively deteriorated. On the other hand, creatinine dialysate/plasma ratio remained within normal limits for about several months, and the increase in the level of serum creatinine was very little. The peritoneum obtained at autopsy revealed marked fibrous thickening as well as the conspicuous luminal narrowing of arteries and veins due to intimal thickening. The development of peritoneal sclerosis seemed to be related with the frequency and severity of peritonitis and the use of hyperosmotic dialysate

Identical Strength of the T Cell Responses against E2, nsP1 and Capsid CHIKV Proteins in Recovered and Chronic Patients after the Epidemics of 2005-2006 in La Reunion Island

<div><p>To characterize the immunity developed by patients infected by chikungunya virus (CHIKV), we studied the intensity and specificity of CHIKV-specific T cells mediated responses in chronic and recovered patients at 12 to 24 months post-infection. T cells were challenged in vitro against CHIKV synthetic peptides covering the length of three viral proteins, capsid, E2 and nsP1 proteins as well as all inactivated virus particles. Cytokine production was assessed by ELISPOT and intracellular labeling. T cells producing IFN-γ were detected against CHIKV in 85% patient’s cells either by direct ELISPOT assay (69% of patients) or after expansion of memory T cells allowing the detection of both CD4 and CD8 specific-T cells in 16% additional cases. The IFN-γ response was mainly engaged in response to nsP1 or E2 (52% and 46% cases, respectively) but in only 27% cases against the capsid. The anti-E2 response represented half the magnitude of the total CHIKV IFN-γ production and was mainly directed against the C-terminal half part of the protein. Almost all patients had conserved a T cell specific response against CHIKV with a clear hierarchy of T cell responses (CD8 > CD4) engaged against E2 > nsP1 > capsid. More importantly, the intensity of responses was not significantly different between recovered and chronic patients. These findings constitute key elements to a better understanding of patient T cell immunoreactivity against CHIKV and argue against a possible defect of T cell immunoresponse in the chronicity post-CHIKV infection.</p> </div

The specific CD4 versus CD8 anti-CHIKV T cell responses.

<p>After stimulation, PBMC from 7 non CHIKV-responders in ELISpot (NRp) were challenged against CHIKV E2, nsP1 or capsid pools of peptides. The reactivity of T CD4+ and T CD8+ cells producing IFN-γ or IL-2 was evaluated by intra-cellular cytokine staining and was detected in only 6 of the 7 NRps. For each condition, the number or responders (left scale) and the percentages of T cell response (means ± SEM, right scale) are indicated. Significant differences in the percentage of cell response measured using Mann–Whitney U test are indicated (p values). Ndt (Not detected).</p

Ex vivo IFN-γ response against CHIKV E2, nsP1 or capsid and EBV.

<p>PBMCs from 48 patients were tested using an IFN-γ ELISpot after challenging against CHIKV E2, capsid or nsP1 pools of peptides or EBV. A) Profile of the T cell specific response to CHIKV compared to EBV. B) Positive correlation between the IFN-γ T cell response against CHIKV and EBV. The correlation (r) and p values are indicated. C) Anti-EBV IFN-γ T cell response between anti-CHIKV responders and Non-Responders. D) Distribution of the IFN-γ response of patients PBMC according to their clinical status. A & D) For each condition, the percentage or responders (bars) and the corresponding intensity of response against CHIKV (number of spot-forming cells (SFC)) expressed as means ± SEM per million of PBMC (dots) are represented.</p