Carsten Schmidt-Weber

Publications (73) View all

• Source

  Available from: Radoslaw Spiewak

  Article: Research needs in allergy: an EAACI position paper, in collaboration with EFA.

  Nikolaos G Papadopoulos, Ioana Agache, Sevim Bavbek, Beatrice M Bilo, Fulvio Braido, Victoria Cardona, Adnan Custovic, Jan Demonchy, Pascal Demoly, Philippe Eigenmann, [......], Ines Swoboda, Ingrid Terreehorst, Elina Toskala, Claudia Traidl-Hoffmann, Carina Venter, Berber Vlieg-Boerstra, Paul Whitacker, Margitta Worm, Paraskevi Xepapadaki, Cezmi A Akdis
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  ABSTRACT: In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.
  Clinical and translational allergy. 11/2012; 2(1):21.
• Article: Pollen metabolome analysis reveals adenosine as a major regulator of dendritic cell-primed T(H) cell responses.

  Stefanie Gilles, Agnes Fekete, Xin Zhang, Isabelle Beck, Cornelia Blume, Johannes Ring, Carsten Schmidt-Weber, Heidrun Behrendt, Philippe Schmitt-Kopplin, Claudia Traidl-Hoffmann
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  ABSTRACT: Water-soluble components from pollen modulate dendritic cell (DC) functions, such as IL-12 secretion and 3'-5'-cyclic adenosine monophosphate (cAMP) signaling and migration, possibly contributing to the establishment of a T(H)2-dominated immune response against pollen. Because these effects could not solely be attributed to the previously identified pollen-associated lipid mediators, the pollen metabolome was analyzed for candidate immunomodulatory substances. We sought to perform an analysis of the effect of pollen-associated adenosine on DC function and T(H) cell differentiation. Fractions of aqueous pollen extracts (APEs) were generated by means of ultrafiltration and were subjected simultaneously to biological tests and metabolome analysis (ultra-high-resolution mass spectrometry) and ultraperformance liquid chromatography. Effects of pollen-derived adenosine on monocyte-derived DC cAMP signaling, cytokine response, and capacity to differentiate T(H) cells were studied. The less than 3-kd fraction of APEs comprised thousands of substances, including adenosine in micromolar concentrations. Pollen-derived adenosine mediated A₂ receptor-dependent induction of cAMP and inhibition of IL-12p70 in DCs. APEs digested with adenosine deaminase failed to mediate IL-12 inhibition. DCs of nonatopic donors exposed to APEs showed an adenosine-dependent reduced capacity to differentiate T(H)1 cells and an enhanced capacity to induce regulatory T cells and IL-10. DCs of atopic donors failed to induce IL-10 but instead induced IL-5 and IL-13. This study identifies adenosine out of thousands of metabolites as a potent immunoregulatory substance in pollen. It acts on the level of the DC, with differential effects in atopic and nonatopic donors.
  The Journal of allergy and clinical immunology 02/2011; 127(2):454-461.e1-9. · 9.17 Impact Factor
• Article: IL-17 and IL-22: siblings, not twins.

  Stefanie Eyerich, Kilian Eyerich, Andrea Cavani, Carsten Schmidt-Weber
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  ABSTRACT: T helper (Th) cell subsets secrete cytokines that regulate other immune cells. Interleukin (IL)-17 and IL-22 belong to a new class of cytokines with predominant effects on epithelial cells. Thus, these cytokines are key molecules in several disease processes. IL-17 and IL-22 are released by leukocytes such as Th and natural killer cell populations. Both IL-17 and IL-22 induce an innate immune response in epithelial cells, but their functional spectra are generally distinct. IL-17 induces an inflammatory tissue response and is involved in the pathogenesis of several autoimmune diseases, whereas IL-22 is protective/regenerative. This review juxtaposes IL-17 and IL-22 and describes overlaps and differences regarding their cellular sources, biochemical structure, signaling cascades in target cells, and function.
  Trends in Immunology 09/2010; 31(9):354-61. · 10.40 Impact Factor
• Article: New T-helper subsets controlling the immune system and tissue cells.

  Carsten Schmidt-Weber
  Immunotherapy 07/2010; 2(4):427-9. · 1.85 Impact Factor
• Article: Immunosuppression affects CD4+ mRNA expression and induces Th2 dominance in the microenvironment of cutaneous squamous cell carcinoma in organ transplant recipients.

  Maria Kosmidis, Piotr Dziunycz, Mayte Suárez-Fariñas, Beda Mühleisen, Leo Schärer, Severin Läuchli, Jürg Hafner, Lars E French, Carsten Schmidt-Weber, John A Carucci, Günther F L Hofbauer
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  ABSTRACT: Squamous cell carcinoma (SCC) is the most frequent cancer in organ transplant recipients (OTRs). The immune system plays a major role in the fight against SCC, however, little is known about the local inflammatory response in SCC at all. We analyzed quantity and quality of the perineoplastic inflammatory SCC microenvironment in immunocompetent patients and immmunosuppressed OTRs. RNA expression profile of SCC patients was analyzed for 8 different sets of genes relating to Th1 versus Th2 response using Gene Set Enrichment Analysis. SCC from immunocompetent patients and OTRs were analyzed by real-time polymerase chain reactions for CD4, CD8, TBET, GATA-3, FOXP3, RORC, IFN-gamma, IL-4, TGF-beta, IL-10, and IL-17A mRNA expression. Immunohistochemistry was carried out in SCC for CD3, CD4, CD8, and FOXP3 expression. Considerable inflammation was seen in both patient groups. SCC in immunocompetent patients and OTRs was associated with a mixed Th1 and Th2 gene expression signature. CD4(+) mRNA was diminished in immunosuppression. Skin adjacent to SCC in OTRs showed Th2 expression pattern as compared with immunocompetent patients. T-BET and IFN-gamma mRNA expression were decreased in the OTR group. Although Th17-weighted inflammation was unchanged, IL-17A mRNA level was markedly decreased with immunosuppression. Regulatory T cells, characterized by FOX-P3 and TGF-beta mRNA level, were decreased in OTRs. Our findings support the hypothesis that nontumor-bearing skin adjacent to SCC in OTRs is not necessarily normal and that the local microenvironment may contribute to a field effect contributing to higher recurrence rates and more aggressive behavior observed in these patients.
  Journal of immunotherapy (Hagerstown, Md.: 1997) 06/2010; 33(5):538-46. · 3.20 Impact Factor