Humboldt University of Berlin

About: Humboldt University of Berlin is a education organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 33671 authors who have published 61781 publications receiving 1908102 citations. The organization is also known as: Humboldt-Universität zu Berlin & Universitas Humboldtiana Berolinensis.

Gene map of the extended human MHC

Abstract: The major histocompatibility complex (MHC) is the most important region in the vertebrate genome with respect to infection and autoimmunity, and is crucial in adaptive and innate immunity. Decades of biomedical research have revealed many MHC genes that are duplicated, polymorphic and associated with more diseases than any other region of the human genome. The recent completion of several large-scale studies offers the opportunity to assimilate the latest data into an integrated gene map of the extended human MHC. Here, we present this map and review its content in relation to paralogy, polymorphism, immune function and disease.

Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences.

Abstract: Cytochrome P450 2D6 (CYP2D6) metabolizes many important drugs CYP2D6 activity ranges from complete deficiency to ultrafast metabolism, depending on at least 16 different known alleles Their frequencies were determined in 589 unrelated German volunteers and correlated with enzyme activity measured by phenotyping with dextromethorphan or debrisoquine For genotyping, nested PCR-RFLP tests from a PCR amplificate of the entire CYP2D6 gene were developed The frequency of the CYP2D6*1 allele coding for extensive metabolizer (EM) phenotype was 364 The alleles coding for slightly (CYP2D6*2) or moderately (*9 and *10) reduced activity (intermediate metabolizer phenotype [IM]) showed frequencies of 324, 018, and 015, respectively By use of novel PCR tests for discrimination, CYP2D6 gene duplication alleles were found with frequencies of 005 (*1x2), 013 (*2x2), and 001 (*4x2) Frequencies of alleles with complete deficiency (poor metabolizer phenotype [PM]) were 207 (*4), 020 (*3 and *5), 009 (*6), and 001 (*7, *15, and *16) The defective CYP2D6 alleles *8, *11, *12, *13, and *14 were not found All 41 PMs (70%) in this sample were explained by five mutations detected by four PCR-RFLP tests, which may suffice, together with the gene duplication test, for clinical prediction of CYP2D6 capacity Three novel variants of known CYP2D6 alleles were discovered: *1C (T1957C), *2B (additional C2558T), and *4E (additional C2938T) Analysis of variance showed significant differences in enzymatic activity measured by the dextromethorphan metabolic ratio (MR) between carriers of EM/PM (mean MR = 006) and IM/PM (mean MR = 014) alleles and between carriers of one (mean MR = 009) and two (mean MR = 003) functional alleles The results of this study provide a solid basis for prediction of CYP2D6 capacity, as required in drug research and routine drug treatment

2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus

Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.

A novel influenza A virus mitochondrial protein that induces cell death

Abstract: While searching for alternative reading-frame peptides encoded by influenza A virus that are recognized by CD8+ T cells, we found an abundant immunogenic peptide encoded by the +1 reading frame of PB1. This peptide derives from a novel conserved 87-residue protein, PB1-F2, which has several unusual features compared with other influenza gene products in addition to its mode of translation. These include its absence from some animal (particularly swine) influenza virus isolates, variable expression in individual infected cells, rapid proteasome-dependent degradation and mitochondrial localization. Exposure of cells to a synthetic version of PB1-F2 induces apoptosis, and influenza viruses with targeted mutations that interfere with PB1-F2 expression induce less extensive apoptosis in human monocytic cells than those with intact PB1-F2. We propose that PB1-F2 functions to kill host immune cells responding to influenza virus infection.