Improving Step by Step

Throughout the past years we stepwise modified our immunosuppressive treatment regimen for patients with antibody-mediated rejection (ABMR). Here, we describe three consecutive groups treated with different regimens. From 2005 until 2008, we treated all patients with biopsy-proven ABMR with rituximab (500 mg), low-dose (30 g) intravenous immunoglobulins (IVIG), and plasmapheresis (PPH, 6x) (group RLP, ). Between 2009 and June 2010, patients received bortezomib (1.3 mg/m2, 4x) together with low-dose IVIG and PPH (group BLP, ). In July 2010, we increased the IVIG dose and treated all subsequent patients with bortezomib, high-dose IVIG (1.5 g/kg), and PPH (group BHP, ). Graft survival at three years after treatment was 73% in group BHP as compared to 45% in group BLP and 25% in group RLP. At six months after treatment median serum creatinine was 2.1 mg/dL, 2.9 mg/dL, and 4.2 mg/dL in groups BHP, BLP, and RLP, respectively (). Following treatment, a significant decrease of donor-specific HLA antibody (DSA) mean fluorescence intensity from to () was observed in group BHP, but not in the other groups. Our results indicate that graft survival, graft function, and DSA levels could be improved along with stepwise modifications to our treatment regimen, that is, the introduction of bortezomib and high-dose IVIG treatment

Predictive value of cytokine gene polymorphisms for the development of end-stage renal disease.

BACKGROUND: Cytokines play a crucial role in different immunopathological conditions. Cytokine secretion is reported to be determined by polymorphisms in the cytokine genes. Since TNF-alfa and IL-10 are involved in regulation of inflammation, and TGF-beta 1 can induce fibrosis and renal insufficiency - dominant features of end-stage renal disease (ESRD), we explored the hypothesis that polymorphisms of these cytokine genes may be possible genetic susceptibility factors for the progression of renal failure. METHODS: We studied the IL-10 (-1082), TNF-alfa (-308), TGF-beta 1 (codon 10;25) gene single nucleotide polymorphisms in 118 healthy donors and 103 patients with ESRD (44 hemodialysis patients with diabetic nephropathy and 59 hemodialysis patients with glomerulonephritis) using PCR-SSP. RESULTS: Significant associations of ESRD with the TGF-beta 1 (codon 10) TT (odds ratio [OR] = 5.31; 95% confidence interval [95% CI], 3.77-7.02; p CONCLUSIONS: Carriage of the TGF-beta 1 (codon 10) TT and IL-10 (-1082) GG genotypes may increase susceptibility to ESRD in German patients with type 2 diabetes or glomerulonephritis

Association of human leukocyte antigen haplotypes with posttransplant lymphoproliferative disease after solid organ transplantation

Background. Posttransplant lymphoproliferative disease (PTLD) after solid organ transplantation (SOT) is commonly characterized by Epstein-Barr virus (EBV)-driven proliferation of recipient B cells due to impaired immune surveillance in the context of immunosuppression. Because EBV-specific T-cell responses are focused on the level of EBV antigen and epitope choice depending on the individual human leukocyte antigen (HLA) alleles, we hypothesized that certain HLA alleles or a distinct HLA haplotype may influence the risk of development of PTLD after SOT. Methods. A multicenter case-control study was performed comparing a group of 155 recipients after SOT with development of PTLD with a group of 1996 recipients after SOT without development of PTLD. Alleles, genotypes, and three locus haplotypes were compared of SOT recipients with and without PTLD. Results. The bivariate analysis showed that carrying HLA-A03 was negatively associated (odds ratio [OR] 0.61, confidence interval [CI] 0.40-0.92, P <0.02) whereas carrying of HLA-B 18 (OR 1.79, CI 1.18-2.73, P <0.006) and HLA-B21 (OR 2.08, CI 1.14-3.77, P <0.02) were positively associated with PTLD after SOT. HLA-DR analysis demonstrated a significant negative association between the expression of HLA-DR7 (OR 0.46, CI 0.28-0.78, P <0.004) and PTLD. Three locus haplotype analysis underlined the relevance of a dominant protective effect of HLA-DR7 expression concerning the risk of PTLD development. Conclusions. Our data suggest an influence of HLA variants on the risk of the development of PTLD. We hypothesize that HLA genes or non-HLA genes within the HLA loci confer a risk modification for the individual patient