Benno Schnyder
University of Bern
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Featured researches published by Benno Schnyder.
Journal of Clinical Investigation | 1997
Benno Schnyder; Daniela Mauri-Hellweg; Martin P. Zanni; Florence Bettens; Werner J. Pichler
T cells can recognize small molecular compounds like drugs. It is thought that covalent binding to MHC bound peptides is required for such a hapten stimulation. Sulfamethoxazole, like most drugs, is not chemically reactive per se, but is thought to gain the ability to covalently bind to proteins after intracellular drug metabolism. The purpose of this study was to investigate how sulfamethoxazole is presented in an immunogenic form to sulfamethoxazole-specific T cell clones. The stimulation of four CD4(+) and two CD8(+) sulfamethoxazole-specific T cell clones by different antigen-presenting cells (APC) was measured both by proliferation and cytolytic assays. The MHC restriction was evaluated, first, by inhibition using anti-class I and anti-class II mAb, and second, by the degree of sulfamethoxazole-induced stimulation by partially matched APC. Fixation of APC was performed with glutaraldehyde 0.05%. The clones were specific for sulfamethoxazole without cross-reaction to other sulfonamides. The continuous presence of sulfamethoxazole was required during the assay period since pulsing of the APC was not sufficient to induce proliferation or cytotoxicity. Stimulation of clones required the addition of MHC compatible APC. The APC could be fixed without impairing their ability to present sulfamethoxazole. Sulfamethoxazole can be presented in an unstable, but MHC-restricted fashion, which is independent of processing. These features are best explained by a direct, noncovalent binding of sulfamethoxazole to the MHC-peptide complex.
Journal of Clinical Investigation | 1998
Martin P. Zanni; S von Greyerz; Benno Schnyder; K A Brander; Karin Frutig; Yvonne Hari; S Valitutti; Werner J. Pichler
T cell recognition of drugs is explained by the hapten-carrier model, implying covalent binding of chemically reactive drugs to carrier proteins. However, most drugs are nonreactive and their recognition by T cells is unclear. We generated T cell clones from allergic individuals specific to sulfamethoxazole, lidocaine (nonreactive drugs), and cef-triaxone (per se reactive beta-lactam antibiotic) and compared the increase of intracellular free calcium concentration ([Ca2+]i) and the kinetics of T cell receptor (TCR) downregulation of these clones by drug-specific stimulations. All drugs tested induced an MHC-restricted, dose- and antigen-presenting cell (APC)-dependent TCR downregulation on specific CD4(+) and CD8(+) T cell clones. Chemically nonreactive drugs elicited an immediate and sustained [Ca2+]i increase and a rapid TCR downregulation, but only when these drugs were added in solution to APC and clone. In contrast, the chemically reactive hapten ceftriaxone added in solution needed > 6 h to induce TCR downregulation. When APC were preincubated with ceftriaxone, a rapid downregulation of the TCR and cytokine secretion was observed, suggesting a stable presentation of a covalently modified peptide. Our data demonstrate two distinct pathways of drug presentation to activated specific T cells. The per se reactive ceftriaxone is presented after covalent binding to carrier peptides. Nonreactive drugs can be recognized by specific alphabeta+ T cells via a nonconventional presentation pathway based on a labile binding of the drug to MHC-peptide complexes.
Journal of Immunology | 2000
Benno Schnyder; Christoph Burkhart; Karin Schnyder-Frutig; Salome von Greyerz; Dean J. Naisbitt; Munir Pirmohamed; B. Kevin Park; Werner J. Pichler
The recognition of the antibiotic sulfamethoxazole (SMX) by T cells is usually explained with the hapten-carrier model. However, recent investigations have revealed a MHC-restricted but processing- and metabolism-independent pathway of drug presentation. This suggested a labile, low-affinity binding of SMX to MHC-peptide complexes on APC. To study the role of covalent vs noncovalent drug presentation in SMX allergy, we analyzed the proliferative response of PBMC and T cell clones from patients with SMX allergy to SMX and its reactive oxidative metabolites SMX-hydroxylamine and nitroso-SMX. Although the great majority of T cell clones were specific for noncovalently bound SMX, PBMC and a small fraction of clones responded to nitroso-SMX-modified cells or were cross-reactive. Rapid down-regulation of TCR expression in T cell clones upon stimulation indicated a processing-independent activation irrespective of specificity for covalently or noncovalently presented Ag. In conclusion, our data show that recognition of SMX presented in covalent and noncovalent bound form is possible by the same TCR but that the former is the exception rather than the rule. The scarcity of cross-reactivity between covalently and noncovalently bound SMX suggests that the primary stimulation may be directed to the noncovalently bound SMX.
Clinical & Experimental Allergy | 2001
Yvonne Hari; K. Frutig-Schnyder; M. Hurni; Nikhil Yawalkar; Martin P. Zanni; Benno Schnyder; A. Kappeler; S. Von Greyerz; L.R. Braathen; Werner J. Pichler
Background The most frequent side‐effects of drug therapy are skin eruptions. Their pathomechanism is rather unclear.
International Archives of Allergy and Immunology | 1999
Benno Schnyder; Arthur Helbling; Werner J. Pichler
Background: Chronic urticaria is a common disease, though only few data on its natural course are available. In most cases the cause cannot be determined. Recently a relationship of chronic urticaria to infection with Helicobacter pylori (HP) has been postulated, but no controlled study has been performed to prove this association. Methods: In this prospective study the clinical course and rate of HP infection in 46 patients with chronic ‘idiopathic’ urticaria were investigated. Infected patients were treated in a double–blind placebo–controlled crossover study with amoxycillin and lansoprazol. Eradication and clinical course were followed up 2 months after each treatment, respectively, 3 and 6 months after the first consultation. Results: In 19/46 (41%) the chronic ‘idiopathic’ urticaria resolved within 6 months. 12 patients (24%) were infected with HP, which corresponds to the infection rate of the population at comparable ages without urticaria in Switzerland. Eradication of HP was achieved in 3, but only in 1 was the eradication associated with the resolution of urticaria. Conclusions: Our data show that in young patients with a rather short history of chronic urticaria frequently a rather favourable natural course of chronic idiopathic urticaria can be seen. No association between HP infection and chronic urticaria could be demonstrated.
Allergy | 2013
K Scherer; K. Brockow; Werner Aberer; Jhc Gooi; P. Demoly; Antonino Romano; Benno Schnyder; P Whitaker; Jsr Cernadas; Andreas J. Bircher
Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV‐positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre‐existent sensitization has not been proven by positive skin tests. Successful re‐administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the Drug Hypersensitivity Interest Group of the European Academy of Allergy and Clinical Immunology.
International Archives of Allergy and Immunology | 1997
Werner J. Pichler; Martin P. Zanni; S. von Greyerz; Benno Schnyder; D. Mauri-Hellweg; Thomas Wendland
To analyze whether and how T cells are involved in drug allergies, we analyzed the drug-induced activation of T cell subsets, T cell receptor V-beta usage and cytokine secretion of T cells from the peripheral blood of drug-allergic individuals. The specificity of the T cells was demonstrated by specific restimulation of drug specific clones. We found that drugs which do not need to be metabolized to become immunogenic (haptens like penicillin G) can stimulate CD4+ and CD8+ T cells in vitro. The T cell response to penicillin can be oligoclonal (use of a certain T cell receptor Vbeta only) or polyclonal. Only polyclonal T cell lines were cross-reactive with other beta-lactam antibiotics. Sulfamethoxazole and lidocaine are thought to gain their ability to bind to proteins by intracellular drug metabolism. They were found to stimulate CD4+ and CD8+ T cells in vitro, and some reactive T cell lines were oligoclonal. The majority of lidocaine-specific clones secreted rather high amounts of IL-5 and IL-4 after PMA/ionomycin stimulations (Th2-like), but some CD4+ and all CD8+ clones had a Th1-like phenotype (high INF-gamma and TNF-alpha). The data clearly demonstrate the existence of drug-specific alphabeta+ T cells in the circulation of drug-allergic individuals and reveal a great heterogeneity of T-cell-mediated responses. Further studies are needed to correlate the type of T cell response to the clinical picture, which can be quite heterogeneous.
The Journal of Allergy and Clinical Immunology | 2008
Ulrich R. Müller; Marek Jutel; Andrea Reimers; Judith Zumkehr; Clarissa Huber; Carola Kriegel; Urs C. Steiner; Gabrielle Haeberli; Mübeccel Akdis; Arthur Helbling; Benno Schnyder; Kurt Blaser; Cezmi A. Akdis
BACKGROUND H1 antihistamines increase safety during allergen-specific immunotherapy and might influence the outcome because of immunoregulatory effects. OBJECTIVE We sought to analyze the influence of 5 mg of levocetirizine (LC) on the safety, efficacy, and immunologic effects of ultrarush honeybee venom immunotherapy (BVIT). METHOD In a double-blind, placebo-controlled study 54 patients with honeybee venom allergy received LC or placebo from 2 days before BVIT to day 21. Side effects during dose increase and systemic allergic reactions (SARs) to a sting challenge after 120 days were analyzed. Allergen-specific immune response was investigated in skin, serum, and allergen-stimulated T-cell cultures. RESULTS Side effects were significantly more frequent in patients receiving placebo. Four patients receiving placebo dropped out because of side effects. SARs to the sting challenge occurred in 8 patients (6 in the LC group and 2 in the placebo group). Seven SARs were only cutaneous, and 1 in the placebo group was also respiratory. Difference of SARs caused by the sting challenge was insignificant. Specific IgG levels increased significantly in both groups. Major allergen phospholipase A(2)-stimulated T cells from both groups showed a slightly decreased proliferation. The decrease in IFN-gamma and IL-13 levels with placebo was not prominent with LC, whereas IL-10 levels showed a significant increase in the LC group only. Decreased histamine receptor (HR)1/HR2 ratio in allergen-specific T cells on day 21 in the placebo group was prevented by LC. CONCLUSIONS LC reduces side effects during dose increase without influencing the efficacy of BVIT. LC modulates the natural course of allergen-specific immune response and affects the expression of HRs and cytokine production by allergen-specific T cells.
European Journal of Immunology | 2012
Jacqueline Adam; Klara Eriksson; Benno Schnyder; Stefano Fontana; Werner J. Pichler; Daniel Yerly
The antiretroviral drug abacavir (abc) elicits severe drug hypersensitivity reactions in HLA‐B*5701+ individuals. To understand the abc‐specific activation of CD8+ T cells, we generated abc‐specific T‐cell clones (abc‐TCCs). Abc reactivity could not be linked to the metabolism and/or processing of the drug, since abc metabolizing enzymes were not expressed in immune cells and inhibition of the proteasome in APCs did not affect TCC reactivity. Ca2+ influx assays revealed different reactivity patterns of abc‐TCCs. While all TCCs reacted to abc presented on HLA‐B*5701 molecules, a minority also reacted immediately to abc in solution. Titration experiments showed that the ability to react immediately to abc correlated significantly with the TCR avidity of the T cells. Modifications of soluble abc concentrations revealed that the reactivity patterns of abc‐TCCs were not fixed but dynamic. When TCCs with an intermediate TCR avidity were stimulated with increasing abc concentrations, they showed an accelerated activation kinetic. Thus, they reacted immediately to the drug, similar to the reaction of TCCs of high avidity. The observed immediate activation and the noninvolvement of the proteasome suggest that, in contrast to haptens, abc‐specific T‐cell stimulation does not require the formation of covalent bonds to produce a neo‐antigenic determinant.
Allergy | 2012
P. Kopac; M. Rudin; Thomas Gentinetta; R. Gerber; Ch. Pichler; Oliver Hausmann; Benno Schnyder; Werner J. Pichler
To cite this article: Kopac P, Rudin M, Gentinetta T, Gerber R, Pichler C, Hausmann O, Schnyder B, Pichler WJ. Continuous apple consumption induces oral tolerance in birch‐pollen‐associated apple allergy. Allergy 2012; 67: 280–285.