Jan Däbritz

Bio: Jan Däbritz is an academic researcher from University of Rostock. The author has contributed to research in topics: Inflammatory bowel disease & Inflammation. The author has an hindex of 21, co-authored 70 publications receiving 1254 citations. Previous affiliations of Jan Däbritz include University of Münster & Royal Children's Hospital.

Diagnostic value of [ 18 F]-FDG PET/CT in children with fever of unknown origin or unexplained signs of inflammation

Abstract: Purpose Fever of unknown origin (FUO) and unexplained signs of inflammation are challenging medical problems especially in children and predominantly caused by infections, malignancies or noninfectious inflammatory diseases. The aim of this study was to assess the diagnostic value of 18F-FDG PET and PET/CT in the diagnostic work-up in paediatric patients.

Limitations and Off-Target Effects of Tryptophan-Related IDO Inhibitors in Cancer Treatment

Abstract: Immunooncology is still a growing area in cancer therapy. Drugs within this therapeutic approach do not directly target/attack the tumor but interfere with immune checkpoints and target or reprogram key metabolic pathways critical for anti-cancer immune defense. Indolamine 2,3-dioxygenase 1 (IDO1) and the tryptophan (TRP)-kynurenine pathway were identified as critical mechanisms in cancer immune escape and their inhibition as an approach with promising therapeutic potential. Particularly, a multitude of IDO1 inhibiting tryptophan analogs are widely applied in several clinical trials. However, this therapy results in a variety of implications for the patient's physiology. This is not only due to the inhibition of an enzyme important in almost every organ and tissue in the body but also because of the general nature of the inhibitor as an analog of a proteinogenic amino acid as well as the initiation of cellular detoxification known to affect inflammatory pathways. In this review we provide a deeper insight into the physiological consequences of an IDO1 inhibiting therapy based on TRP related molecules. We discuss potential side and off-target effects that contribute to the interpretation of unexpected positive as well as negative results of ongoing or discontinued clinical studies while we also highlight the potential of these inhibitors independent of the IDO1 signaling pathway.

Detection of Ki-ras mutations in tissue and plasma samples of patients with pancreatic cancer using PNA-mediated PCR clamping and hybridisation probes.

Abstract: In the present study, we combined the PCR-clamping approach with melting curve analysis using mutant specific hybridisation probes and wild-type specific peptide nucleic acids (PNAs) to determine the genotypes of the most frequent point mutation in codon 12 of the proto-oncogene Ki-ras in tissue and plasma samples of patients with pancreatic cancer. The sensitivity of our assay was 1–5 × 10−5. The melting curve analysis of tissue samples of four patients revealed two valine mutations, one none-valine mutation and one wild-type sequence. Ki-ras alterations were found in 28% of DNAs (18 out of 64) of nonrelated plasma samples of 10 patients with ductal adenocarcinoma of the pancreas. The valine mutation was the predominantly detected gene alteration (83%). Out of ten patients investigated, four patients (40%) became positive during clinical observation with respect to Ki-ras mutation. All four patients exhibited progressive disease and high levels of tumour marker CA 19-9. In conclusion, the one-step procedure discribed may be a useful clinical tool for analysing Ki-ras point mutations in tissue and plasmas samples. In addition, this method can be adapted for simultanous detection of multiple mutations and quantitation.

Improving relapse prediction in inflammatory bowel disease by neutrophil-derived S100A12.

Abstract: Background Prediction of inflammatory bowel disease relapse has important implications for therapeutic strategies. Fecal S100A12 has been reported as a novel marker of intestinal inflammation. The objective was to investigate the utility of S100A12 as a marker for the confirmation of stable remission and prediction of relapses. Methods We consecutively included 147 adults and 34 children with Crohn's disease (n = 61) or ulcerative colitis (n = 120). Over a 3-year period, we collected 686 stool samples and 861 serum samples during regular follow-up visits. S100A12 and calprotectin levels were measured by an enzyme-linked immunoassay. Results Fecal S100A12 correlated with S100A12 serum levels, other laboratory markers, as well as disease activity, location, and behavior. Fecal S100A12 levels in the relapse group differed significantly from those of the nonrelapse group. A baseline fecal S100A12 level of >0.5 mg/kg was significantly associated with disease relapse within 18 months. Time course analysis of fecal S100A12 before and after relapse showed a clear increase of S100A12 concentrations up to 6 months before clinical relapse. At 0.43 mg/kg, the sensitivity and specificity of S100A12 for predicting relapse already 8 to 12 weeks earlier were 70% and 83%, respectively. Conclusions Regular measurements of fecal S100A12 levels reliably detect inflammatory bowel disease relapse at an early stage, which makes the test a promising noninvasive tool for monitoring and optimizing therapy, and may reduce the need for invasive investigations during disease follow-up.

Follow-up study of K-ras mutations in the plasma of patients with pancreatic cancer: correlation with clinical features and carbohydrate antigen 19-9.

Abstract: OBJECTIVE We followed up the presence of Kirsten rat sarcoma (K-ras) mutations in plasma DNA and assessed its clinical value in patients with pancreatic cancer. METHODS Plasma samples (N = 430) of 56 patients with pancreatic cancer and 13 patients with pancreatitis were analyzed by real-time polymerase chain reaction using peptide nucleic acid-mediated polymerase chain reaction clamping. RESULTS K-ras mutations could be detected in the plasma DNA of 20 patients with cancer (36%). No K-ras mutation was found in the plasma of patients with pancreatitis. In 7 (35%) of 20 patients with lowly or moderately elevated carbohydrate antigen 19.9 (CA 19-9) levels lower than 100 U/mL, the result of the assay was positive for K-ras mutation. The combination of K-ras and CA 19-9 level determination gave a sensitivity for the diagnosis of pancreatic cancer of 91% (40/44) of the patients. Thirteen of 35 patients with pancreatic cancer (102 plasma samples) with elevated CA 19-9 levels (>35 U/mL) and altered K-ras gene showed significant correlation with elevated CA 19-9 levels (P=0.048). CONCLUSIONS The summary of our approach of noninvasive, convenient, extremely high-sensitive K-ras mutation analysis in plasma might provide diagnostic and prognostic information to clinicians but will not be sufficient in a standardized early diagnosis of pancreatic carcinoma. The combination with CA 19-9 assay is useful for detection and prognostic evaluation of pancreatic carcinoma.

Irf5 promotes inflammatory macrophage polarization and th1/th17 response

Abstract: Polymorphisms in the gene encoding the transcription factor IRF5 that lead to higher mRNA expression are associated with many autoimmune diseases. Here we show that IRF5 expression in macrophages was reversibly induced by inflammatory stimuli and contributed to the plasticity of macrophage polarization. High expression of IRF5 was characteristic of M1 macrophages, in which it directly activated transcription of the genes encoding interleukin 12 subunit p40 (IL-12p40), IL-12p35 and IL-23p19 and repressed the gene encoding IL-10. Consequently, those macrophages set up the environment for a potent T helper type 1 (TH1)-TH17 response. Global gene expression analysis demonstrated that exogenous IRF5 upregulated or downregulated expression of established phenotypic markers of M1 or M2 macrophages, respectively. Our data suggest a critical role for IRF5 in M1 macrophage polarization and define a previously unknown function for IRF5 as a transcriptional repressor.

Discovery and characterization of chromatin states for systematic annotation of the human genome

Abstract: A plethora of epigenetic modifications have been described in the human genome and shown to play diverse roles in gene regulation, cellular differentiation and the onset of disease. Although individual modifications have been linked to the activity levels of various genetic functional elements, their combinatorial patterns are still unresolved and their potential for systematic de novo genome annotation remains untapped. Here, we use a multivariate Hidden Markov Model to reveal chromatin states in human T cells, based on recurrent and spatially coherent combinations of chromatin marks.We define 51 distinct chromatin states, including promoter-associated, transcription-associated, active intergenic, largescale repressed and repeat-associated states. Each chromatin state shows specific enrichments in functional annotations, sequence motifs and specific experimentally observed characteristics, suggesting distinct biological roles. This approach provides a complementary functional annotation of the human genome that reveals the genome-wide locations of diverse classes of epigenetic function.