Detection of IgE-autoantibodies to nuclear antigens in patients with systemic sclerosis and analysis of their clinical relevance.

OBJECTIVES: Antinuclear antibodies (ANA) of the IgE-type have been described in several connective tissue disorders (CTD) but not yet in systemic sclerosis (SSc). Aim of the study was, therefore, to establish an ELISA for the demonstration of IgE-autoantibodies to topoisomerase-I (topo-I) and the centromeric proteins A and B (CENP-A/B), to assess their prevalence and reactivity in SSc and to analyse their clinical relevance. METHODS: One hundred fifty-one patients with SSc and 88 with CREST-syndrome, 291 patients with other CTD, and 23 patients with fibromyalgia syndrome (FM) as a control collective were included into the study. Patients' sera were analysed by an in-house-ELISA for IgE autoantibodies against topo-I and CENP-A/B using recombinant antigens. Patients were assessed for median Rodnan skin score(mRSS), different organ and cutaneous manifestations. RESULTS: Of the patients with CREST syndrome, 67% had IgE-anti-CENP-A- and 77% IgE-anti-CENP-B-antibodies. IgE-anti-topo-I antibodies were found in 56% of patients with SSc. Prevalence and reactivity were significantly higher in CREST and SSc, respectively, than in other CTD or FM. IgE-reactivity strongly correlated with IgG-antibody reactivity. In CRESTsyndrome, IgE-anti-CENP-A (but not CENP-B)-antibodies were significantly higher and more prevalent in patients with skin ulcers, high mRSS, and more than four organ manifestations. They did not correlate with blood eosinophil counts. In contrast, for IgE-anti-topo-I antibodies no correlation with clinical manifestations was observed. CONCLUSIONS: IgE-autoantibodies against CENP-A/B and topo-I occur in SSc underlining the concept that SSc may be a T helper cell type 2 mediated disease. IgE-anti-CENP-A-antibodies correlated with disease activity, but this has to be confirmed in larger studies.

Dual antibody induction and de novo use of everolimus enable low-dose tacrolimus with early corticosteroid withdrawal in simultaneous pancreas-kidney transplantation.

BACKGROUND: To be an optimal immunosuppressive regimen after simultaneous pancreas kidney transplantation (SPK), low dose calcineurin inhibitor and early withdrawal of corticosteroids are desired. METHODS: Immunosuppressive regimen as such has been conducted consecutively in SPK recipients since 2009 in authors' institute. In addition to tacrolimus in low trough level and early corticosteroid withdraw, dual induction with basiliximab and low-dose thymoglobulin in combination with everolimus are the important components of the protocol. RESULTS: 25 consecutive primary SPK recipients were included in the study. Lymphocyte depletion by low dose thymoglobulin was limited to two weeks, and CD25 coating with basiliximab was detectable for 4 weeks. The BPAR within the first 12 months was 13%. During a median follow-up of 58 months, new-onset diabetes mellitus and renal function deterioration were rare events. No cytomegalovirus activation was encountered. The patients, pancreas and kidney graft survival at 1-year and 5-year was 100% and 94.4%, 95.8% and 95.8%, 100% and 100% respectively.

Role of the Fyn -93A>G polymorphism (rs706895) in acute rejection after liver transplantation.

The tyrosine kinase Fyn phosphorylates tyrosine residues on key targets involved in early T-cell signal transduction. T-cell signal transduction is one essential step for acute transplant rejection. The aim of this study was to evaluate the association of Fyn -93A>G single nucleotide polymorphism (SNP) (rs706895) with the susceptibility to acute rejection episodes in liver transplantation. In total, 72 liver transplant recipients with one biopsy proven acute rejection (S-BPAR), 56 with multiple BPAR (M-BPAR), 105 without BPAR (No-BPAR), and 145 healthy controls were enrolled in this case-control study. The SNP was genotyped by polymerase chain reaction-allele specific restriction enzyme analysis (PCR-ASRA) and was analyzed for a recessive and a dominant model. The Fyn -93G allele exhibits in healthy controls a statistically significant lower frequency than in liver recipients (18% vs. 24%; p=0.046) or in liver recipients with BPAR (18% vs. 27%; p=0.017). However, the genotype and allele frequencies of the Fyn -93A>G SNP demonstrate no significant differences between recipients with acute rejection episodes (S-BPAR and M-BPAR) and No-BPAR recipients. Thus our results provide no evidence that the Fyn -93A>G SNP contributes to the susceptibility to acute liver transplant rejection in a Caucasian population.

Lack of association between CD40 polymorphisms and acute rejection in German liver transplant recipients.

CD40 and its ligand, CD154, are major costimulatory molecules whose interactions are important in alloreactive transplant rejection. The aim of this study was to examine the association of CD40 polymorphisms with the susceptibility to acute rejection episodes in liver transplantation. In total, 112 liver transplant recipients with biopsy proven acute rejections (BPAR), 97 without BPAR (WBPAR), and 112 healthy control individuals were enrolled in the study. Two single nucleotide polymorphisms (SNPs) of CD40 gene (rs1883832 and rs4810485) were genotyped by polymerase chain reaction-allele specific restriction enzyme analysis (PCR-ASRA). Both SNPs has been tested for a recessive and a dominant model. No significant differences were found in the genotype and allele frequencies of the SNPs rs1883832 and rs4810485 between BPAR liver recipients and WBPAR recipients. Our results do not suggest an important role of tested CD40 SNPs in the susceptibility to acute liver transplant rejection in a Caucasian population.