Meta-analysis identifies seven susceptibility loci involved in the atopic march.

Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance.

UNLABELLED Patients carrying very rare loss-of-function mutations in interleukin-1 receptor-associated kinase 4 (IRAK4), a critical signaling mediator in Toll-like receptor signaling, are severely immunodeficient, highlighting the paramount role of IRAK kinases in innate immunity. We discovered a comparatively frequent coding variant of the enigmatic human IRAK2, L392V (rs3844283), which is found homozygously in ∼15% of Caucasians, to be associated with a reduced ability to induce interferon-alpha in primary human plasmacytoid dendritic cells in response to hepatitis C virus (HCV). Cytokine production in response to purified Toll-like receptor agonists was also impaired. Additionally, rs3844283 was epidemiologically associated with a chronic course of HCV infection in two independent HCV cohorts and emerged as an independent predictor of chronic HCV disease. Mechanistically, IRAK2 L392V showed intact binding to, but impaired ubiquitination of, tumor necrosis factor receptor-associated factor 6, a vital step in signal transduction. CONCLUSION Our study highlights IRAK2 and its genetic variants as critical factors and potentially novel biomarkers for human antiviral innate immunity.

Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of "omic" datasets that are at the core of this systems medicine approach.

David Kaufmann [Rezension]

C. G.

Hofrat Professor Dr. David Heinrich v. Müller

G. Rosenmann

Na 1 Nachlass Max Horkheimer, 690 - Materialien zu Forschungsprojekten über Antisemitismus u.a. (p. IX 157 - IX 163.1-9)

"Beitrag des Instituts für Sozialforschung zu dem Forschungsprojekt über Autorität" (3.1.1951). Typoskript, 5 Blatt; "Reactions to the Antisemitic Incidents in January 1960. A Pilot Study in Frankfurt am Main. Summary of Procedure and Results" (1960). Typoskript, 6 Blatt (= Alt.Sig. IX 234.13 a); "Proposal for International Study of Anti-Semitism" (1960):; 1. American Jewish Committee: Luncheon Meeting, May 25, 1960, Typoskript, 2 Blatt; 2. American Jewish Committee, Institute of Human Relations: "The JDA Agencies and Germany" (17.5.1960). Als Typoskript vervielfältigt, 32 Blatt; Exzerpte aus Werken über Antisemitismus, Literaturlisten (etwa 1933-46):; 1. Everett R. Clinchy, Typoskript, 1 Blatt; 2. Paul K. Hatt, Typoskript, 3 Blatt; 3. John Moffat Mecklin, Typoskript, 3 Blatt; 4. Conrad Henry Moehlman, Typoskript, 4 Blatt; 5. Maurice Samuel, Typoskript, 5 Blatt; 6. Milton Steinberg, Typoskript, 2 Blatt; 7. "General Literature on Antisemitism", Liste, Typoskript mit handschriftlichen Ergänzungen, 1 Blatt; 8. "Bibliography" zum Judentum, 15 Blatt; 9. Literaturliste, handschriftliche Notizen, 9 Blatt; 10. Literaturliste, eigenhändige Notizen von Max Horkheimer, 1 Blatt; 11. Literaturliste, 1 Blatt; 12. Zitate zum Judentum aus Zeitschriften, 1 Blatt; Memorandum zum Antisemitismus (1944-48):; 1. S. Andhil Fineberg: "Notes on 'A Mask for Privilege' by Carey McWilliams", als Typoskript vervielfältigt, 4 Blatt; Carey McWilliams: "Memorandum" (8.5.1948), Typoskript, 3 Blatt; Lawrence Bloomgarden und S.A. Fineberg: "In Reply to Carey McWilliams Memorandum of May 8th", Typoskript, 3 Blatt; 2. Rundbriefe der American Jewish Sociological Society, 1944, als Typoskript vervielfältigt, 4 Blatt; 3. Bericht über einen Vortrag von Wladimir Eliasberg über Antisemitismus, Typoskript, 1 Blatt; Abschriften und Übersetzungen aus Zeitungsartikeln über Antisemitismus (1939-43):; 1. "A Note on Anti-Semitism", aus: The New Statesman and Nation (13.3.1939), Typoskript, 7 Blatt; 2. Abschriften aus deutschen und englischen Zeitungen, 1939, Typoskript, 1 Blatt; 3. "A Homility of the Bishop of Cremona" (Übersetzung aus: Osservatore Romano) 1939. Typoskript, 18 Blatt; Veröffentlichungen über Antisemitismus, Vorurteil, Demagogie (1941-63):; 1. Earl Raab und Seymour M. Lipset: "Prejudice and Society", Freedom Pamphlet Anti-Defamation League of B'nai B'rith (New York 1963), 48 Seiten; 2. Committee on Education, Training and Research in Race Relations of the University of Chicago: Bulletin, Nr. 1, 30.6.1948, 55. Seiten; 3. Solomon Andhil Fineberg: "Checkmate for Rabble-Rousers. What to Do When the Demagogue Comes to Town", Sonderdruck aus Commentary, Vol. 2, 1946 und eine Broschüre, 20 Seiten; 4. Kurt Lewin: "A new Approach to Old Problems", aus: Congress Week, 19.1.1945, 2 Blatt; 5. Eric A. Johnston: "Intolerance", New York, 11.1.1945, Heft, 8 Blatt; 6. Philip Wylie: "Memorandum on Anti-Semitism", aus: American Mercury, Januar 1945, 5 Blatt; 7. S.I. Hayakawa: "Race and Words", aus: Common Sense, Juli 1943, 3 Blatt; 8. David Riesman: "The Politics of Persecution". Als Typoskript vervielfältigt, 21 Blatt; 9. James P. Gifford, Frank D. Schroth, Maximilian Moss, Edward A. Richards, Samuel J. Levinson, Thomas G. Grace: "Anti-Semitism. It's Causes and Cures", New York, 1941, 30 Seiten;

Katalog der hebräischen Handschriften und Bücher in der Bibliothek des Professors Dr. David Kaufmann

beschrieben von Max Weisz