Karine Gastaldello

Evidence that pentoxifylline reduces anti-CD3 monoclonal antibody-induced cytokine release syndrome.

Pretreatment with pentoxifylline (PTX), a methylxanthine known for its beneficial effects on tissue lesions induced by the injection of endotoxin or recombinant cytokines, was shown to decrease the systemic release of tumor necrosis factor and interleukin 2 occurring after the administration of the anti-CD3 monoclonal antibody 145–2C11 in mice. In parallel, PTX attenuated the hypothermia and the rise in blood urea nitrogen observed in this model. The protective effect of PTX on the toxicity of 145–2C11 was confirmed by the reduction of the mortality among D-galactosamine-sensitized animals. The mitigation by PTX of the release of cytokines did not affect the immunosuppression entailed by 145–2C11 as assessed by the unmodified cytotoxic T lymphocytes (CTL) unresponsiveness against alloantigens measured 48 hr after the injection of the mAb. In vitro experiments on human peripheral blood leu

Influenza A/H1N1 Vaccine in Patients Treated by Kidney Transplant or Dialysis: A Cohort Study

BACKGROUND AND OBJECTIVES In 2009, the pandemic influenza A/H1N1 accounted for worldwide recommendations about vaccination. There are few data concerning the immunogenicity or the security of the adjuvanted-A/H1N1 vaccine in transplanted and hemodialyzed patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Sera from 21 controls, 53 hemodialyzed (HD) patients, and 111 renal transplant recipients (RT) were sampled before (T0) and 1 month after (T1) a single dose of Pandemrix® vaccine (GSK Biologicals, AS03-adjuvanted). We measured the neutralizing antibodies against A/H1N1/2009, the geometric mean (GM) titers, the GM titer ratios (T1/T0) with 95% confidence intervals, and the seroconversion rate (responders: ≥4-fold increase in titer). The HLA and MICA immunization was determined by Luminex technology. RESULTS The GM titer ratio was 38 (19 to 78), 9 (5 to 16), and 5 (3 to 6) for controls, HD patients, and RT patients, respectively (P < 0.001). The proportion of responders was 90%, 57%, and 44%, respectively (P < 0.001). In RT patients, the prevalence of histocompatibility leukocyte antigen (HLA) class I, histocompatibility leukocyte antigen class II, and MHC class I-related chain A immunization, was, respectively, 15%, 14%, and 14% before and 14%, 14%, and 11% after vaccination (P = 1, 1, and 0.39). CONCLUSIONS The influenza A/H1N1-adjuvanted vaccine is of limited efficacy but is safe in renal disease populations. The humoral response is lower in transplanted versus hemodialyzed patients. Further studies are needed to improve the efficacy of vaccination in those populations.

Cuprophane haemodialysis induces upregulation of LPS receptor (CD14) on monocytes: role of complement activation

BACKGROUND The CD14 molecule is a high-affinity receptor for the complex formed by lipopolysaccharide (LPS) and LPS-binding protein. METHODS We examined by flow cytometry the effect of in vitro and in vivo haemodialysis on cuprophane membrane and recombinant C5a on the expression of CD14 molecules at the surface on monocytes. Monocyte CD14 expression was also studied during in vitro and in vivo haemodialysis on polyacrylonitrile AN69 membrane. RESULTS In vitro haemodialysis of whole blood from healthy volunteers on cuprophane membrane resulted within 30 min in upregulation of monocyte CD14 expression. The reuse of the cuprophane membrane abolished both complement activation and CD14 upregulation. Moreover, incubation of whole blood with recombinant C5a led to an increased monocyte CD14 expression supporting a role for complement activation in the rapid cuprophane-induced CD14 upregulation. During AN69 dialysis which is not associated with complement activation in the blood phase, monocyte CD14 expression did not change during the first 60 min but was significantly increased after 3 h of in vitro haemodialysis. This late increase might be related to the presence of complement activation products adsorbed on the membrane. In vivo dialysis on cuprophane membrane also resulted in early monocyte CD14 upregulation as indicated by higher CD14 expression found after 60 min on monocytes obtained from the efferent as compared to the afferent line of the dialyser, a phenomenon that was not observed during haemodialysis on AN69 membrane. CONCLUSION Haemodialysis on the complement-activating cuprophane membrane induces the rapid upregulation of the CD14 LPS-receptor on monocytes.

Sarcoma-like pyogenic granuloma of the thumb and respiratory restrictive syndrome in a non-compliant hemodialysis patient.

Pyogenic granuloma is a benign vascular tumor of the skin or mucosae usually observed after irritative processes. We report the case of a non-compliant hemodialysis patient with severe hyperparathyroidism who rapidly developed growing pyogenic granuloma of the distal part of the left thumb. This tumor mimicked sarcoma and caused recurrent bleeding during hemodialysis sessions. Hand radiograph revealed an osteolytic lesion compatible with a brown tumor. Among other brown tumors, several of those found in the ribs were responsible of a severe respiratory restrictive deficit. This report highlights the difficulty to choose the adequate treatment of severe hyperparathyroidism, and discusses the benefit/risk balance of performing parathyroidectomy.