Publications (14) View all
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Article: The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immunthyroiditis and autoimmune diabetes.
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ABSTRACT: The lymphoid tyrosine phosphatase (LYP) encoded by the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a strong inhibitor of T cells. The single nucleotide polymorphism (SNP) C1858T within the PTPN22 gene was recently associated with autoimmune thyroid disease (AITD) and type I diabetes (T1D). The purpose of this study was to examine the joint association of this polymorphism with the co-occurrence of AITD and T1D. In this association study, 310 white subjects were genotyped for the C1858T polymorphism. The study population included 70 patients with both AITD and T1D (AITD+T1D), 70 patients with AITD only, 70 patients with T1D only, and 100 healthy controls. Patients with both AITD and T1D, and controls were also typed for HLA-DRB1. PTPN22 C1858T genotyping was performed by minisequencing. For HLA-DRB1 typing, polymerase chain reaction (PCR) sequence-specific oligonucleotide probes were used. The PTPN22 1858 minor T-allele frequency was strongly increased in patients with AITD+T1D (23.6%) compared with controls (8.0%, pc<0.001), with patients with AITD only (8.6%, pc=0.006), or with T1D only (10.7%, pc=0.028). T-allele carriers were also more frequently present in the group with AITD+T1D versus controls (41.4% vs. 14.0%, OR=4.35, 95% CI=2.08-9.09), AITD (17.1%, OR=3.42, 95% CI=1.56-7.48), and T1D (21.4%, OR=2.59, 95% CI=1.23-5.45). Especially in subjects with Hashimoto's thyroiditis (HT)+T1D, T-allele carriers were mostly frequent (50% vs. 14%, OR=6.14, 95% CI=2.62-14.38, pc<0.001). Considering all included patients with AITD, T-allele carriers were 29.3% vs. 14.0% in controls (p=0.008, OR=2.54, 95% CI=1.30-4.98). Patients carrying the PTPN22 1858 T allele had a twofold increased frequency of the HLA-DRB1*03 allele (64.7% vs. 37.3%, pc=0.034). The PTPN22 gene is a joint susceptibility locus for AITD (especially HT) and T1D.Thyroid: official journal of the American Thyroid Association 12/2008; 19(2):143-8. · 2.60 Impact Factor -
Article: New alleles and mutational events at 14 STR loci from different German populations.
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ABSTRACT: The molecular origin of DNA mutations and the mutation rates were analyzed at 14 short tandem repeat (STR) loci with samples from trio cases derived from 10 different German population samples. STR loci comprised of D2S1360, D3S1744, D4S2366, D5S2500, D6S474, D7S1517, D8S1132, D10S2325, D12S391, D18S51, D19S246, D20S480, D21S226, and D22S689. In a total of 488 meioses, 16 isolated genetic inconsistencies in 8 different STRs were observed, whereas no mutations were found at the other loci. The data of five mutations suggested the presence of silent or null alleles due to sequence variation in primer binding site. This could be confirmed for four suspected cases by the use of alternative primer sets and by DNA sequence analyses. Furthermore, this study revealed nine new allelic variants at five different loci.Forensic science international. Genetics 01/2008; 1(3-4):232-7. · 2.42 Impact Factor -
Article: Forensic validation of the SNPforID 52-plex assay.
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ABSTRACT: The advantages of single nucleotide polymorphism (SNP) typing in forensic genetics are well known and include a wider choice of high-throughput typing platforms, lower mutation rates, and improved analysis of degraded samples. However, if SNPs are to become a realistic supplement to current short tandem repeat (STR) typing methods, they must be shown to successfully and reliably analyse the challenging samples commonly encountered in casework situations. The European SNPforID consortium, supported by the EU GROWTH programme, has developed a multiplex of 52 SNPs for forensic analysis, with the amplification of all 52 loci in a single reaction followed by two single base extension (SBE) reactions which are detected with capillary electrophoresis. In order to validate this assay, a variety of DNA extracts were chosen to represent problems such as low copy number and degradation that are commonly seen in forensic casework. A total of 40 extracts were used in the study, each of which was sent to two of the five participating laboratories for typing in duplicate or triplicate. Laboratories were instructed to carry out their analyses as if they were dealing with normal casework samples. Results were reported back to the coordinating laboratory and compared with those obtained from traditional STR typing of the same extracts using Powerplex 16 (Promega). These results indicate that, although the ability to successfully type good quality, low copy number extracts is lower, the 52-plex SNP assay performed better than STR typing on degraded samples, and also on samples that were both degraded and of limited quantity, suggesting that SNP analysis can provide advantages over STR analysis in forensically relevant circumstances. However, there were also additional problems arising from contamination and primer quality issues and these are discussed.Forensic science international. Genetics 07/2007; 1(2):186-90. · 2.42 Impact Factor -
Article: Zwei Mechanismen fuhren zur UV-induzierten Aktivierung des Transkriptionsfaktors NF-kB : ein DNA-Schaden-abhangiger und ein -unabhangiger Prozess /
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ABSTRACT: Thesis--Universitat Karlsruhe, (1997?). -
Article: Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell-depleted reduced-intensity transplantation.
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ABSTRACT: Allogeneic hematopoietic stem cell transplantation (SCT) regimens incorporating the lymphocytotoxic CD52 antibody alemtuzumab demonstrate efficient engraftment and reduced graft-versus-host disease (GVHD). However, these protocols substantially impair posttransplantation antiviral and antitumor immunity. To accelerate immune reconstitution after alemtuzumab-based reduced-intensity SCT, we administered prophylactic CD8-depleted donor lymphocyte infusions (DLIs) starting on days 60 and 120 after transplantation. DLIs were processed in an immunomagnetic good manufacturing practice depletion procedure resulting in a 2.5- to 6-log reduction in CD8 T cells. Of 23 high-risk patients with hematologic malignancies, 11 received a total of 21 CD8-depleted DLIs. Five patients developed transient grade I acute GVHD following transfer. Only 2 patients with HLA-C-mismatched donors showed grade II and III acute GVHD and subsequently progressed to limited chronic GVHD. Following DLIs, 4 patients with declining hematopoietic donor chimerism converted to full chimeras. A 2.1-fold median increase of circulating CD4 T cells was observed within 2 weeks after infusion. Non-DLI patients did not show a comparable rise in CD4 counts. Four patients demonstrated enhanced frequencies of cytomegalovirus-specific CD4 and CD8 T cells following transfer. Our results suggest that prophylactic CD8-depleted DLIs accelerate immune reconstitution after lymphodepleted HLA-matched SCT and carry a low risk of inducing severe GVHD.Blood 02/2007; 109(1):374-82. · 9.90 Impact Factor
