The diagnostic hallmark of MMF-related colitis is an IBD-like histological pattern in association with increased epithelial apoptosis, while apoptotic cell death seems to be a potential pathogenetic factor of mucosa injury.

IntroductionIt has been proposed that individual genetic variation contributes to the course of severe infections and sepsis. Recent studies of single nucleotide polymorphisms (SNPs) within the endotoxin receptor and its signaling system showed an association with the risk of disease development. This study aims to examine the response associated with genetic variations of TLR4, the receptor for bacterial LPS, and a central intracellular signal transducer (TIRAP/Mal) on cytokine release and for susceptibility and course of severe hospital acquired infections in distinct patient populations.MethodsThree intensive care units in tertiary care university hospitals in Greece and Germany participated. 375 and 415 postoperative patients and 159 patients with ventilator associated pneumonia (VAP) were included. TLR4 and TIRAP/Mal polymorphisms in 375 general surgical patients were associated with risk of infection, clinical course and outcome. In two prospective studies, 415 patients following cardiac surgery and 159 patients with newly diagnosed VAP predominantly caused by Gram-negative bacteria were studied for cytokine levels in-vivo and after ex-vivo monocyte stimulation and clinical course.ResultsPatients simultaneously carrying polymorphisms in TIRAP/Mal and TLR4 and patients homozygous for the TIRAP/Mal SNP had a significantly higher risk of severe infections after surgery (odds ratio (OR) 5.5; confidence interval (CI): 1.34 - 22.64; P = 0.02 and OR: 7.3; CI: 1.89 - 28.50; P < 0.01 respectively). Additionally we found significantly lower circulating cytokine levels in double-mutant individuals with ventilator associated pneumonia and reduced cytokine production in an ex-vivo monocyte stimulation assay, but this difference was not apparent in TIRAP/Mal-homozygous patients. In cardiac surgery patients without infection, the cytokine release profiles were not changed when comparing different genotypes.ConclusionsCarriers of mutations in sequential components of the TLR signaling system may have an increased risk for severe infections. Patients with this genotype showed a decrease in cytokine release when infected which was not apparent in patients with sterile inflammation following cardiac surgery.

Despite improvements in overall prognosis in lupus nephritis, 10%-30% of patients with proliferative renal involvement progress to end stage renal disease, according to the severity of the disease and associated socioeconomic factors. Kidney transplantation has been recognized as the most appropriate treatment for those patients, but several issues remain after renal function restoration in a lupus recipient. Among these are the fear of lupus nephritis recurrence in the graft, the choice of immunosuppressive therapy in cases of recurrent lupus for a patient who has already received a toxic and prolonged immunosuppressive course, and finally, the management of comorbidities to reduce associated morbidities in the long term. All the above topics are examined in this review, with the hope of providing a clear picture of data as illustrated in the current literature.

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IA was shown efficacious in a small series of patients with recurrent FSGS in the graft. Renal function remained stable in eight of the 12 patients with FSGS recurrence.