Publikationsserver der Universitätsbibliothek Marburg
Titel:Immunologische Pathomechanismen bei Spättypallergie auf Betalactamantibiotika
Autor:Schäfer, Carolin
Weitere Beteiligte: Pfützner, W. (Prof. Dr. med.)
Veröffentlicht:2016
URI:https://archiv.ub.uni-marburg.de/diss/z2016/0303
URN: urn:nbn:de:hebis:04-z2016-03036
DOI: https://doi.org/10.17192/z2016.0303
DDC:610 Medizin
Titel (trans.):immunological pathomechanism in case of delayed type hypersensitivity of betalacatam antibiotics
Publikationsdatum:2016-04-20
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Hypersensibilität, allergy, Elispot assay, Allergologie, Penicilline, Betalactamantibiotika, Allergie, delayed type, Spättypallergie, Pathomechanismus, Elispot, betalactam antibiotics

Zusammenfassung:
Die Entwicklung von Allergien ist auf das komplexe Zusammenspiel zwischen genetischen Faktoren und bestimmten Umwelteinflüssen zurückzuführen. Bei etwa 25% der Menschen entwickeln sich überschießende Immunantworten, die durch harmlose Umweltstoffe wie Pollen oder Nahrungsmittel aber auch Arzneimittel ausgelöst werden können. Die Arzneimittelallergie hat in den letzten Jahren stetig an Bedeutung zugenommen. Hierbei kommt es zu einer immunologisch vermittelten Überempfindlichkeit auf ein Medikament, die sich nach den zugrunde liegenden Pathomechanismen als allergische Soforttypreaktion oder als Spättypreaktion nach Coombs und Gell äußern kann. Die Betalactmantibiotika gehören zu den häufigsten Auslösern allergischer Medikamentenreaktionen. Der Pathomechanismus einer Soforttypreaktion auf Penicilline entspricht einer klassischen IgE-vermittelten Reaktion. Demgegenüber steht die Spättypreaktion, bei der es zur Aktivierung spezifischer T-Lymphozyten und zur Sekretion proinflammatorischer Zytokine kommt, durch die schließlich die entsprechenden Hautreaktion in Form eines Exanthems hervorgerufen wird. Die vorliegende Studie wurde mit vier unterschiedlichen Probandengruppen durchgeführt, bei denen Untersuchungen mit verschiedenen Betalactamantibiotika (Penicillin G, Amoxicillin, Ampicillin und Cefuroxim) durchgeführt wurden. Im Fokus der Studie standen dabei Allergiker vom Spättyp. Diese wurden klinisch und immunologisch mit Kollektiven von Soforttypallergikern sowie von nicht-allergischen Individuen mit und ohne Betalactamexposition als Kontrollgruppen verglichen. Zu diesem Zweck wurden allergologische In-vivo-Testverfahren wie Hauttests (Prick-, Intrakutan-, Epikutantest) und die orale Provokationstestung durchgeführt. Auf Basis der hierbei gewonnenen Ergebnisse erfolgte neben der Anamnese die klinische Charakterisierung und Einteilung in die vorab festgelegten Probandengruppen. Durch die anschließenden Verfahren der In-vitro-Diagnostik wurden sowohl allergenspezifische Antikörper im Serum als auch die Frequenzen allergenspezifischer T-Zellpopulationen im peripheren Blut anhand Zell-spezifischer Markerzytokine (IFN-γ, IL-5 und IL-10) bestimmt. Zusätzlich wurde die Frequenz regulatorischer T(reg)-Zellen anhand des Oberflächenmarkerprofils CD4+CD25+CD127low untersucht. Die hierbei ermittelten immunologischen Parameter der Spättypallergiker wurden mit denen der anderen Studienkollektive verglichen. Die Studienergebnisse zeigten eine unauffällige humorale Antwort im Vergleich der vier verschiedenen Probandengruppen. Auf zellulärer Ebene konnte das Kollektiv der Spättypallergiker nicht über die häufig postulierte vermehrte IFN-γ-Sekretion von den anderen drei Patientengruppen abgegrenzt werden, jedoch fand sich eine gesteigerte Th2-Zellantwort bei den Soforttypallergikern. Es ließen sich keine Unterschiede der Anzahl IL-10-sezernierender Tr1-Zellen nach In-vitro-Betalactamstimulation in allen vier Gruppen detektieren, allerdings zeigte sich in der mit Betalactamantibiotika behandelten Kontrollgruppe ein tendenzieller Anstieg von IFN-γ+ und IL-10+ T-Zellen. Dies könnte ein Hinweis für die Induktion eines protektiven Mechanismus bei gesunden Probanden nach Antibiotikastimulation sein. Andererseits fand sich eine tendenzielle Abnahme der CD4+CD25+CD127low Treg-Population in dieser Kontrollgruppe während der dreitägigen systemischen Betalactamtherapie, was die Komplexität möglicher immunologischer Reaktionsmechanismen auf Betalaktamantibiotika unterstreicht. Insofern liefern die Ergebnisse der vorliegenden Arbeit einige interessante Ansatzpunkte für weitere wissenschaftliche Untersuchungen zu dem insgesamt noch sehr wenig erforschten Gebiet der Arzneimittelallergie.

Bibliographie / References

  1. Möbs, C. (2010). "Zelluläre Mechanismen der Toleranzinduktion unter spezifischer Immun- therapie mit inhalativen Allergenen. Marburg, Philipps-Universität Marburg."
  2. Mockenhaupt, M., C. Viboud, et al. (2008). "Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study." J Invest Dermatol 128(1): 35-44.
  3. Beeler, A., O. Engler, et al. (2006). "Long-lasting reactivity and high frequency of drug- specific T cells after severe systemic drug hypersensitivity reactions." J Allergy Clin Immunol 117(2): 455-62.
  4. Beeler, A. and W. J. Pichler (2006). "In vitro tests of T cell-mediated drug hypersensitivity." Expert Rev Clin Immunol 2(6): 887-900.
  5. Pichler, W. J., B. Daubner, et al. "Drug hypersensitivity: flare-up reactions, cross-reactivity and multiple drug hypersensitivity." J Dermatol 38(3): 216-21.
  6. Torres, M. J., C. Mayorga, et al. (2009). "Nonimmediate allergic reactions induced by drugs: pathogenesis and diagnostic tests." J Investig Allergol Clin Immunol 19(2): 80-90.
  7. Bottema, R. W., M. Kerkhof, et al. "X-chromosome Forkhead Box P3 polymorphisms associ- ate with atopy in girls in three Dutch birth cohorts." Allergy 65(7): 865-74.
  8. Meiler, F., S. Klunker, et al. (2008). "Distinct regulation of IgE, IgG4 and IgA by T regulato- ry cells and toll-like receptors." Allergy 63(11): 1455-63.
  9. Akdis, C. A. and M. Akdis (2009). "Mechanisms and treatment of allergic disease in the big picture of regulatory T cells." J Allergy Clin Immunol 123(4): 735-46; quiz 747-8.
  10. Johansson, S. G., T. Bieber, et al. (2004). "Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003." J Allergy Clin Immunol 113(5): 832-6.
  11. Sidoroff, A., S. Halevy, et al. (2001). "Acute generalized exanthematous pustulosis (AGEP)-- a clinical reaction pattern." J Cutan Pathol 28(3): 113-9.
  12. Halken, S. (2004). "Prevention of allergic disease in childhood: clinical and epidemiological aspects of primary and secondary allergy prevention." Pediatr Allergy Immunol 15 Suppl 16: 4-5, 9-32.
  13. Goldmann, O., S. Lehne, et al. "Age-related susceptibility to Streptococcus pyogenes infec- tion in mice: underlying immune dysfunction and strategy to enhance immunity." J Pathol 220(5): 521-9.
  14. Radulovic, S., M. R. Jacobson, et al. (2008). "Grass pollen immunotherapy induces Foxp3- expressing CD4+ CD25+ cells in the nasal mucosa." J Allergy Clin Immunol 121(6): 1467-72, 1472 e1.
  15. Gomes, E., M. F. Cardoso, et al. (2004). "Self-reported drug allergy in a general adult Portu- guese population." Clin Exp Allergy 34(10): 1597-601.
  16. Pereira-Santos, M. C., A. P. Baptista, et al. (2008). "Expansion of circulating Foxp3+)D25bright CD4+ T cells during specific venom immunotherapy." Clin Exp Allergy 38(2): 291-7.
  17. Aberer, W., A. Bircher, et al. (2003). "Drug provocation testing in the diagnosis of drug hy- persensitivity reactions: general considerations." Allergy 58(9): 854-63.
  18. Robinson, D. S., Q. Hamid, et al. (1992). "Predominant TH2-like bronchoalveolar T- lymphocyte population in atopic asthma." N Engl J Med 326(5): 298-304.
  19. Huber, B. (2006). "[100 years of allergy: Clemens von Pirquet--his concept of allergy and his basic understanding of the disease: 2: The Pirquet concept of allergy]." Wien Klin Wochenschr 118(23-24): 718-27.
  20. Thornton, A. M., C. A. Piccirillo, et al. (2004). "Activation requirements for the induction of CD4+CD25+ T cell suppressor function." Eur J Immunol 34(2): 366-76.
  21. Juan, W. H., L. C. Yang, et al. (2004). "Acute generalized exanthematous pustulosis induced by topical lindane." Dermatology 209(3): 239-40.
  22. Kidon, M. I. and Y. See (2004). "Adverse drug reactions in Singaporean children." Singapore Med J 45(12): 574-7.
  23. Riedl, M. A. and A. M. Casillas (2003). "Adverse drug reactions: types and treatment op- tions." Am Fam Physician 68(9): 1781-90.
  24. Jin, C., B. Hantusch, et al. (2008). "Affinity of IgE and IgG against cross-reactive carbohy- drate determinants on plant and insect glycoproteins." J Allergy Clin Immunol 121(1): 185-190 e2.
  25. von Mutius, E. (2007). "Allergies, infections and the hygiene hypothesis--the epidemiological evidence." Immunobiology 212(6): 433-9.
  26. Kay, A. B. (2001). "Allergy and allergic diseases. First of two parts." N Engl J Med 344(1): 30-7.
  27. Ponvert, C., L. Le Clainche, et al. (1999). "Allergy to beta-lactam antibiotics in children." Pediatrics 104(4): e45.
  28. Chaabane, A., K. Aouam, et al. (2009). "[Allergy to betalactams: myth and realities]." Med Mal Infect 39(5): 278-87.
  29. Khattri, R., T. Cox, et al. (2003). "An essential role for Scurfin in CD4+CD25+ T regulatory cells." Nat Immunol 4(4): 337-42.
  30. Lewis, S. A. (2000). "Animals and allergy." Clin Exp Allergy 30(2): 153-7.
  31. Szabo, S. J., S. T. Kim, et al. (2000). "A novel transcription factor, T-bet, directs Th1 lineage commitment." Cell 100(6): 655-69.
  32. Trautmann, A., K. Kruger, et al. (2005). "Apoptosis and loss of adhesion of bronchial epithe- lial cells in asthma." Int Arch Allergy Immunol 138(2): 142-50.
  33. Czerkinsky, C. C., L. A. Nilsson, et al. (1983). "A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells." J Immunol Methods 65(1-2): 109-21.
  34. Padilla, A., R. Ferriols, et al. (2007). "[A time series analysis of the cost of the most common drug treatment groups in an intensive care unit]." Farm Hosp 31(5): 307-10.
  35. Haddi, E., D. Charpin, et al. (1990). "Atopy and systemic reactions to drugs." Allergy 45(3): 236-9.
  36. Riedler, J., W. Eder, et al. (2000). "Austrian children living on a farm have less hay fever, asthma and allergic sensitization." Clin Exp Allergy 30(2): 194-200.
  37. Taylor, A. I., H. J. Gould, et al. (2008). "Avian IgY binds to a monocyte receptor with IgG- like kinetics despite an IgE-like structure." J Biol Chem 283(24): 16384-90.
  38. Shevach, E. M. (2002). "CD4+ CD25+ suppressor T cells: more questions than answers." Nat Rev Immunol 2(6): 389-400.
  39. Carr, T. F. and C. A. Saltoun "Chapter 2: Skin testing in allergy." Allergy Asthma Proc 33 Suppl 1: S6-8.
  40. Schaerli, P., M. Britschgi, et al. (2004). "Characterization of human T cells that regulate neutrophilic skin inflammation." J Immunol 173(3): 2151-8.
  41. Bastuji-Garin, S., B. Rzany, et al. (1993). "Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme." Arch Dermatol 129(1): 92-6.
  42. Nonaka, M., N. Ogihara, et al. (2008). "Combined stimulation of nasal polyp fibroblasts with poly IC, interleukin 4, and tumor necrosis factor alpha potently induces production of thymus-and activation-regulated chemokine." Arch Otolaryngol Head Neck Surg 134(6): 630-5.
  43. Hori, S., T. Takahashi, et al. (2003). "Control of autoimmunity by naturally arising regulatory CD4+ T cells." Adv Immunol 81: 331-71.
  44. Shevach, E. M., R. S. McHugh, et al. (2001). "Control of T-cell activation by CD4+ CD25+ suppressor T cells." Immunol Rev 182: 58-67.
  45. Wing, K., Y. Onishi, et al. (2008). "CTLA-4 control over Foxp3+ regulatory T cell function." Science 322(5899): 271-5.
  46. Mayorga, C., M. J. Torres, et al. (2009). "Cutaneous symptoms in drug allergy: what have we learnt?" Curr Opin Allergy Clin Immunol 9(5): 431-6.
  47. Enzmann, H. (1980). "[Delayed allergic nasal reactions. (Synonyms: Coombs and Gell's type IV, delayed hypersensitivity, allergy of the tuberculin and eczema type). Studies on the morphology and pathogenesis]." Fortschr Med 98(19): 745-51.
  48. Pichler, W. J. (2003). "Delayed drug hypersensitivity reactions." Ann Intern Med 139(8): 683- 93.
  49. Moll, I. (2010). "Dermatologie, Thieme Verlag."
  50. Rozieres, A., A. Hennino, et al. (2009). "Detection and quantification of drug-specific T cells in penicillin allergy." Allergy 64(4): 534-42.
  51. Asero, R. (1998). "Detection of patients with multiple drug allergy syndrome by elective tol- erance tests." Ann Allergy Asthma Immunol 80(2): 185-8.
  52. Finotto, S., M. F. Neurath, et al. (2002). "Development of spontaneous airway changes con- sistent with human asthma in mice lacking T-bet." Science 295(5553): 336-8.
  53. Seitz, C. S., E. B. Brocker, et al. "Diagnosis of drug hypersensitivity in children and adoles- cents: discrepancy between physician-based assessment and results of testing." Pediatr Allergy Immunol 22(4): 405-10.
  54. Pichichero, M. E. and D. M. Pichichero (1998). "Diagnosis of penicillin, amoxicillin, and cephalosporin allergy: reliability of examination assessed by skin testing and oral challenge." J Pediatr 132(1): 137-43.
  55. Brunkow, M. E., E. W. Jeffery, et al. (2001). "Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse." Nat Genet 27(1): 68-73.
  56. Demoly, P. (2007). "[Drug allergies and drug hypersensitivities]." Rev Prat 57(12): 1326-30.
  57. Thong, B. Y., K. P. Leong, et al. (2003). "Drug allergy in a general hospital: Results of a nov- el prospective inpatient reporting system." Ann Allergy Asthma Immunol 90(3): 342- 7.
  58. Pichler, W. J., J. Adam, et al. (2011). "Drug hypersensitivity reactions: pathomechanism and clinical symptoms." Med Clin North Am 94(4): 645-64, xv.
  59. Shiohara, T., M. Inaoka, et al. (2006). "Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpesviruses and antiviral and anti- drug immune responses." Allergol Int 55(1): 1-8.
  60. Barbaud, A. (2005). "Drug patch testing in systemic cutaneous drug allergy." Toxicology 209(2): 209-16.
  61. Messaad, D., H. Sahla, et al. (2004). "Drug provocation tests in patients with a history sug- gesting an immediate drug hypersensitivity reaction." Ann Intern Med 140(12): 1001- 6.
  62. Ajduk, J., I. Marinic, et al. (2008). "Effect of house dust mite immunotherapy on transforming growth factor beta1-producing T cells in asthmatic children." Ann Allergy Asthma Immunol 100(4): 314-22.
  63. Leonard, J. P., M. L. Sherman, et al. (1997). "Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production." Blood 90(7): 2541-8.
  64. Lindemann, M., J. Bohmer, et al. (2003). "ELISpot: a new tool for the detection of nickel sen- sitization." Clin Exp Allergy 33(7): 992-8.
  65. Ando, D. G., J. Clayton, et al. (1989). "Encephalitogenic T cells in the B10.PL model of ex- perimental allergic encephalomyelitis (EAE) are of the Th-1 lymphokine subtype." Cell Immunol 124(1): 132-43.
  66. Garn, H. and H. Renz (2007). "Epidemiological and immunological evidence for the hygiene hypothesis." Immunobiology 212(6): 441-52.
  67. Gomes, E. R. and P. Demoly (2005). "Epidemiology of hypersensitivity drug reactions." Curr Opin Allergy Clin Immunol 5(4): 309-16.
  68. Campbell, I. L., T. W. Kay, et al. (1991). "Essential role for interferon-gamma and interleu- kin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice." J Clin Invest 87(2): 739-42.
  69. Mittmann, N., S. R. Knowles, et al. (2004). "Evaluation of the extent of under-reporting of serious adverse drug reactions: the case of toxic epidermal necrolysis." Drug Saf 27(7): 477-87.
  70. Seddiki, N., B. Santner-Nanan, et al. (2006). "Expression of interleukin (IL)-2 and IL-7 recep- tors discriminates between human regulatory and activated T cells." J Exp Med 203(7): 1693-700.
  71. Kjellman, N. I. (1987). "Food allergy--treatment and prevention." Ann Allergy 59(5 Pt 2): 168-74.
  72. Zheng, Y. and A. Y. Rudensky (2007). "Foxp3 in control of the regulatory T cell lineage." Nat Immunol 8(5): 457-62.
  73. Abbas, A. K., K. M. Murphy, et al. (1996). "Functional diversity of helper T lymphocytes." Nature 383(6603): 787-93.
  74. Barranco, P. and M. C. Lopez-Serrano (1998). "General and epidemiological aspects of aller- gic drug reactions." Clin Exp Allergy 28 Suppl 4: 61-2.
  75. Brockow, K., A. Romano, et al. (2002). "General considerations for skin test procedures in the diagnosis of drug hypersensitivity." Allergy 57(1): 45-51.
  76. Mullen, A. C., A. S. Hutchins, et al. (2002). "Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction." Nat Immunol 3(7): 652-8.
  77. Ng, W. F., P. J. Duggan, et al. (2001). "Human CD4(+)CD25(+) cells: a naturally occurring population of regulatory T cells." Blood 98(9): 2736-44.
  78. Dieckmann, D., C. H. Bruett, et al. (2002). "Human CD4(+)CD25(+) regulatory, contact- dependent T cells induce interleukin 10-producing, contact-independent type 1-like regulatory T cells [corrected]." J Exp Med 196(2): 247-53.
  79. Del Prete, G., M. De Carli, et al. (1993). "Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific prolifer- ation and cytokine production." J Immunol 150(2): 353-60.
  80. Romagnani, S. (1994). "Human TH1 and TH2 subsets: "eppur si muove"!" Eur Cytokine Netw 5(1): 7-12.
  81. Comte, D., S. Petitpierre, et al. "[Hymenoptera venom allergy: new diagnostic tools and man- agement]." Rev Med Suisse 7(291): 844-9.
  82. Niggemann, B. "IgE-mediated latex allergy--an exciting and instructive piece of allergy histo- ry." Pediatr Allergy Immunol 21(7): 997-1001.
  83. Jutel, M., M. Akdis, et al. (2003). "IL-10 and TGF-beta cooperate in the regulatory T cell re- sponse to mucosal allergens in normal immunity and specific immunotherapy." Eur J Immunol 33(5): 1205-14.
  84. Wills-Karp, M. (2001). "IL-12/IL-13 axis in allergic asthma." J Allergy Clin Immunol 107(1): 9-18.
  85. Blease, K., C. Jakubzick, et al. (2001). "IL-13 fusion cytotoxin ameliorates chronic fungal- induced allergic airway disease in mice." J Immunol 167(11): 6583-92.
  86. Korn, T., E. Bettelli, et al. (2009). "IL-17 and Th17 Cells." Annu Rev Immunol 27: 485-517.
  87. Dabbagh, K., K. Takeyama, et al. (1999). "IL-4 induces mucin gene expression and goblet cell metaplasia in vitro and in vivo." J Immunol 162(10): 6233-7.
  88. Gomez, M. B., M. J. Torres, et al. (2004). "Immediate allergic reactions to betalactams: facts and controversies." Curr Opin Allergy Clin Immunol 4(4): 261-6.
  89. Torgerson, T. R. and H. D. Ochs (2007). "Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: forkhead box protein 3 mutations and lack of regulatory T cells." J Allergy Clin Immunol 120(4): 744-50; quiz 751-2.
  90. Gomez, E., M. J. Torres, et al. "Immunologic evaluation of drug allergy." Allergy Asthma Immunol Res 4(5): 251-63.
  91. Sakaguchi, S., N. Sakaguchi, et al. (1995). "Immunologic self-tolerance maintained by acti- vated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases." J Immunol 155(3): 1151-64.
  92. Huang, H. and W. E. Paul (1998). "Impaired interleukin 4 signaling in T helper type 1 cells." J Exp Med 187(8): 1305-13.
  93. Romagnani, S., E. Maggi, et al. (1991). "Increased numbers of Th2-like CD4+ T cells in tar- get organs and in the allergen-specific repertoire of allergic patients. Possible role of IL-4 produced by non-T cells." Int Arch Allergy Appl Immunol 94(1-4): 133-6.
  94. Smart, J. M. and A. S. Kemp (2002). "Increased Th1 and Th2 allergen-induced cytokine re- sponses in children with atopic disease." Clin Exp Allergy 32(5): 796-802.
  95. Bettelli, E., T. Korn, et al. (2008). "Induction and effector functions of T(H)17 cells." Nature 453(7198): 1051-7.
  96. Gabrielsson, S., A. Soderlund, et al. (2001). "Influence of atopic heredity on IL-4-, IL-12-and IFN-gamma-producing cells in in vitro activated cord blood mononuclear cells." Clin Exp Immunol 126(3): 390-6.
  97. Meves, A. (2006). "Intensivkurs Dermatolgie.Elsevier / Urban & Fischer Verlag."
  98. Roncarolo, M. G., S. Gregori, et al. (2006). "Interleukin-10-secreting type 1 regulatory T cells in rodents and humans." Immunol Rev 212: 28-50.
  99. Wills-Karp, M., J. Luyimbazi, et al. (1998). "Interleukin-13: central mediator of allergic asthma." Science 282(5397): 2258-61.
  100. Pochard, P., P. Gosset, et al. (2002). "Lactic acid bacteria inhibit TH2 cytokine production by mononuclear cells from allergic patients." J Allergy Clin Immunol 110(4): 617-23.
  101. Howard, T. D., D. A. Meyers, et al. (2000). "Mapping susceptibility genes for asthma and allergy." J Allergy Clin Immunol 105(2 Pt 2): S477-81.
  102. von Boehmer, H. (2005). "Mechanisms of suppression by suppressor T cells." Nat Immunol 6(4): 338-44.
  103. Mayorga, C., R. R. Pena, et al. (2006). "Monitoring the acute phase response in non- immediate allergic drug reactions." Curr Opin Allergy Clin Immunol 6(4): 249-57.
  104. Jäger, L. W., B.;Ballmer-Weber,B.;Vieths,S. (2000). "Nahrungsmittelallergien und - intoleranzen: Immunologie -Diagnostik -Therapie -Prophylaxe. Urban & Fischer Verlag, Stuttgart."
  105. Curotto de Lafaille, M. A. and J. J. Lafaille (2009). "Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor?" Immunity 30(5): 626-35.
  106. Sakaguchi, S. (2004). "Naturally arising CD4+ regulatory t cells for immunologic self- tolerance and negative control of immune responses." Annu Rev Immunol 22: 531-62.
  107. Sakaguchi, S. (2005). "Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self." Nat Immunol 6(4): 345-52.
  108. Terrados, S., M. Blanca, et al. (1995). "Nonimmediate reactions to betalactams: prevalence and role of the different penicillins." Allergy 50(7): 563-7.
  109. WHO (1966). "Organisation W H International drug monitoring."
  110. Wantke, F. and S. Wöhrl (2008). "Penicillinallergie." 10-13.
  111. Cetinkaya, F. and Y. Cag (2004). "Penicillin sensitivity among children without a positive history for penicillin allergy." Pediatr Allergy Immunol 15(3): 278-80.
  112. Ruby, P., F. Collette, et al. (2009). "Perspective taking to assess self-personality: what's modi- fied in Alzheimer's disease?" Neurobiol Aging 30(10): 1637-51.
  113. Majkowska-Wojciechowska, B., J. Pelka, et al. (2007). "Prevalence of allergy, patterns of allergic sensitization and allergy risk factors in rural and urban children." Allergy 62(9): 1044-50.
  114. Bettelli, E., Y. Carrier, et al. (2006). "Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells." Nature 441(7090): 235-8.
  115. Renzi, P. M., J. P. Turgeon, et al. (1999). "Reduced interferon-gamma production in infants with bronchiolitis and asthma." Am J Respir Crit Care Med 159(5 Pt 1): 1417-22.
  116. Bonnefoy, J. Y., J. F. Gauchat, et al. (1996). "Regulation of human IgE synthesis." Ann N Y Acad Sci 796: 59-71.
  117. Chen, Y., V. K. Kuchroo, et al. (1994). "Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis." Science 265(5176): 1237-40.
  118. Beissert, S., A. Schwarz, et al. (2006). "Regulatory T cells." J Invest Dermatol 126(1): 15-24.
  119. Ziegler, S. F. (2008). "Regulatory T cells and inflammation: better late than never." Immunity 29(1): 5-7.
  120. Peterson, R. A. "Regulatory T-cells: diverse phenotypes integral to immune homeostasis and suppression." Toxicol Pathol 40(2): 186-204.
  121. Humrich, J. and G. Riemekasten (2006). "[Regulatory T cells in rheumatic diseases]." Dtsch Med Wochenschr 131(41): 2288-91.
  122. Romagnani, S. (2006). "Regulatory T cells: which role in the pathogenesis and treatment of allergic disorders?" Allergy 61(1): 3-14.
  123. Aktories, K. F., U;Hofmann,F.B.;Starke,K. (2009). "Repititorium Allgemeine und spezielle Pharmakologie und Toxikologie, Urban & Fischer Verlag, München."
  124. Pamphilon, D. H. and M. L. Scott (2007). "Robin Coombs: his life and contribution to haema- tology and transfusion medicine." Br J Haematol 137(5): 401-8.
  125. Hazlett, L. D., X. L. Rudner, et al. (2002). "Role of IL-12 and IFN-gamma in Pseudomonas aeruginosa corneal infection." Invest Ophthalmol Vis Sci 43(2): 419-24.
  126. Rozieres, A., M. Vocanson, et al. (2009). "Role of T cells in nonimmediate allergic drug reac- tions." Curr Opin Allergy Clin Immunol 9(4): 305-10.
  127. Palomares, O., G. Yaman, et al. (2010). "Role of Treg in immune regulation of allergic dis- eases." Eur J Immunol 40(5): 1232-40.
  128. Schulz, E. G., L. Mariani, et al. (2009). "Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12." Immunity 30(5): 673- 83.
  129. Carr, T. F. and C. A. Saltoun (2012). "Chapter 2: Skin testing in allergy." Allergy Asthma Proc 33 Suppl 1: S6-8.
  130. Grindebacke, H., P. Larsson, et al. (2009). "Specific immunotherapy to birch allergen does not enhance suppression of Th2 cells by CD4(+)CD25(+) regulatory T cells during pollen season." J Clin Immunol 29(6): 752-60.
  131. Bircher, A. (2007). " Stellenwert des Lymphozytentransformationstests in der Diagnostik der Arzneimittelallergie." Allergo Journal 2007.
  132. Borchers, A. T., J. L. Lee, et al. (2008). "Stevens-Johnson syndrome and toxic epidermal necrolysis." Autoimmun Rev 7(8): 598-605.
  133. Bohle, B., T. Kinaciyan, et al. (2007). "Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation." J Allergy Clin Immunol 120(3): 707-13.
  134. Neumann-Haefelin, C., H. C. Spangenberg, et al. (2004). "[Suppressor T-cells: immunologic regulator cells and clinical perspectives]." Dtsch Med Wochenschr 129(30): 1627-30.
  135. Dow, S. W., J. Schwarze, et al. (1999). "Systemic and local interferon gamma gene delivery to the lungs for treatment of allergen-induced airway hyperresponsiveness in mice." Hum Gene Ther 10(12): 1905-14.
  136. Afkarian, M., J. R. Sedy, et al. (2002). "T-bet is a STAT1-induced regulator of IL-12R ex- pression in naive CD4+ T cells." Nat Immunol 3(6): 549-57.
  137. Munthe-Kaas, M. C., K. H. Carlsen, et al. (2008). "T cell-specific T-box transcription factor haplotype is associated with allergic asthma in children." J Allergy Clin Immunol 121(1): 51-6.
  138. Klimek, L. and I. Bottcher (2008). "[T-cells regulate the immune-response in allergic rhini- tis]." Laryngorhinootologie 87(10): 733-43.
  139. Mosmann, T. R. and R. L. Coffman (1989). "TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties." Annu Rev Immunol 7: 145-73.
  140. Mashishi, T. and C. M. Gray (2002). "The ELISPOT assay: an easily transferable method for measuring cellular responses and identifying T cell epitopes." Clin Chem Lab Med 40(9): 903-10.
  141. Uter, W., J. Hegewald, et al. (2005). "The European standard series in 9 European countries, 2002/2003 --first results of the European Surveillance System on Contact Allergies." Contact Dermatitis 53(3): 136-45.
  142. Fujio, K., T. Okamura, et al. "The Family of IL-10-secreting CD4+ T cells." Adv Immunol 105: 99-130.
  143. Rajan, T. V. (2003). "The Gell-Coombs classification of hypersensitivity reactions: a re- interpretation." Trends Immunol 24(7): 376-9.
  144. Nelms, K., A. D. Keegan, et al. (1999). "The IL-4 receptor: signaling mechanisms and biolog- ic functions." Annu Rev Immunol 17: 701-38.
  145. Collison, L. W., C. J. Workman, et al. (2007). "The inhibitory cytokine IL-35 contributes to regulatory T-cell function." Nature 450(7169): 566-9.
  146. Murphy, K. M. and S. L. Reiner (2002). "The lineage decisions of helper T cells." Nat Rev Immunol 2(12): 933-44.
  147. Cohn, L., R. J. Homer, et al. (1999). "T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus production." J Exp Med 190(9): 1309-18.
  148. Pichler, W. J. and J. Tilch (2004). "The lymphocyte transformation test in the diagnosis of drug hypersensitivity." Allergy 59(8): 809-20.
  149. Viinanen, A., S. Munhbayarlah, et al. (2007). "The protective effect of rural living against atopy in Mongolia." Allergy 62(3): 272-80.
  150. Saint-Mezard, P., F. Berard, et al. (2004). "The role of CD4+ and CD8+ T cells in contact hypersensitivity and allergic contact dermatitis." Eur J Dermatol 14(3): 131-8.
  151. Oppenheim, J. and H. Fujiwara (1996). "The role of cytokines in cancer." Cytokine Growth Factor Rev 7(3): 279-88.
  152. Girolomoni, G. and S. Pastore (2001). "The role of keratinocytes in the pathogenesis of atopic dermatitis." J Am Acad Dermatol 45(1 Suppl): S25-8.
  153. Iwakura, Y., S. Nakae, et al. (2008). "The roles of IL-17A in inflammatory immune responses and host defense against pathogens." Immunol Rev 226: 57-79.
  154. Kirchner, D. B. (2002). "The spectrum of allergic disease in the chemical industry." Int Arch Occup Environ Health 75 Suppl: S107-12.
  155. Lammintausta, K. and O. Kortekangas-Savolainen (2005). "The usefulness of skin tests to prove drug hypersensitivity." Br J Dermatol 152(5): 968-74.
  156. Polansky, J. K. and J. Huehn (2007). "[To be or not to be a Treg: epigenetic regulation of Foxp3 expression in regulatory T cells]." Z Rheumatol 66(5): 417-20.
  157. French, L. E. (2006). "Toxic epidermal necrolysis and Stevens Johnson syndrome: our current understanding." Allergol Int 55(1): 9-16.
  158. Mangan, P. R., L. E. Harrington, et al. (2006). "Transforming growth factor-beta induces de- velopment of the T(H)17 lineage." Nature 441(7090): 231-4.
  159. Mosmann, T. R., H. Cherwinski, et al. (2005). "Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. 1986." J Immunol 175(1): 5-14.
  160. Romagnani, S. (1991). "Type 1 T helper and type 2 T helper cells: functions, regulation and role in protection and disease." Int J Clin Lab Res 21(2): 152-8.
  161. Backstrom, M., T. Mjorndal, et al. (2004). "Under-reporting of serious adverse drug reactions in Sweden." Pharmacoepidemiol Drug Saf 13(7): 483-7.
  162. Halevy, S. (2009). "Acute generalized exanthematous pustulosis." Curr Opin Allergy Clin Immunol 9(4): 322-8.
  163. Kramer, U., J. Heinrich, et al. (1999). "Age of entry to day nursery and allergy in later child- hood." Lancet 353(9151): 450-4.
  164. Forster, R., A. Schubel, et al. (1999). "CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs." Cell 99(1): 23-33.
  165. Pichler, W. J., N. Yawalkar, et al. (2002). "Cellular and molecular pathophysiology of cuta- neous drug reactions." Am J Clin Dermatol 3(4): 229-38.
  166. Daubner, B., M. Groux-Keller, et al. (2012). "Multiple drug hypersensitivity: normal Treg cell function but enhanced in vivo activation of drug-specific T cells." Allergy 67(1): 58- 66.
  167. Strachan, D. P. (1989). "Hay fever, hygiene, and household size." Bmj 299(6710): 1259-60.
  168. Hebenstreit, D., P. Luft, et al. (2003). "IL-4 and IL-13 induce SOCS-1 gene expression in A549 cells by three functional STAT6-binding motifs located upstream of the tran- scription initiation site." J Immunol 171(11): 5901-7.
  169. Wolfgang Pfützner, Carolin Intrup, Christian Möbs Predominance of IL-5-secreting drug-specific T cells in subgroups of patients with drug-induced delayed-type hypersensitivity reaction. 2014; -Drug Hypersensitivity Meeting (DHM), Bern Switzerland
  170. Black, C. A. (1999). "Delayed type hypersensitivity: current theories with an historic perspec- tive." Dermatol Online J 5(1): 7.
  171. Pekkarinen, P. T., L. von Hertzen, et al. (2007). "A disparity in the association of asthma, rhinitis, and eczema with allergen-specific IgE between Finnish and Russian Karelia." Allergy 62(3): 281-7.
  172. Basketter, D. A., G. F. Gerberick, et al. (1998). "Strategies for identifying false positive re- sponses in predictive skin sensitization tests." Food Chem Toxicol 36(4): 327-33.
  173. Davies, D. M., C. H. Ashton, et al. (1977). "Comprehensive clinical drug information service: first year's experience." Br Med J 1(6053): 89-90.
  174. Platts-Mills, T. A., J. W. Vaughan, et al. (2001). "Decreased prevalence of asthma among children with high exposure to cat allergen: relevance of the modified Th2 response." Mediators Inflamm 10(6): 288-91.
  175. Wong, C. K., C. Y. Ho, et al. (2001). "Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL- 12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma." Clin Exp Immunol 125(2): 177-83.
  176. Ilona J. Frieden, M. D. a. L. F. E., M.D. (2011). "Pediatric dermatology." ISI Journal Citation Reports © Ranking: 2011: 40/58 (Dermatology); 76/115 (Pediatrics)
  177. Liu, W., A. L. Putnam, et al. (2006). "CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells." J Exp Med 203(7): 1701-11.
  178. Hirai, K., M. Yamaguchi, et al. (1990). "Enhancement of human basophil histamine release by interleukin 5." J Exp Med 172(5): 1525-8.
  179. Iwamoto, I., H. Nakajima, et al. (1993). "Interferon gamma regulates antigen-induced eosino- phil recruitment into the mouse airways by inhibiting the infiltration of CD4+ T cells." J Exp Med 177(2): 573-6.
  180. Akdis, M., J. Verhagen, et al. (2004). "Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells." J Exp Med 199(11): 1567-75.
  181. Sakaguchi, S. (2003). "The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery." J Clin Invest 112(9): 1310-2.
  182. Gri, G., S. Piconese, et al. (2008). "CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction." Immunity 29(5): 771-81.
  183. Korn, T., M. Oukka, et al. (2007). "Th17 cells: effector T cells with inflammatory properties." Semin Immunol 19(6): 362-71.
  184. Nikolich-Zugich, J. and B. D. Rudd "Immune memory and aging: an infinite or finite re- source?" Curr Opin Immunol 22(4): 535-40.
  185. Gundel, R. H., L. G. Letts, et al. (1991). "Human eosinophil major basic protein induces air- way constriction and airway hyperresponsiveness in primates." J Clin Invest 87(4): 1470-3.
  186. Buckner, J. H. "Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases." Nat Rev Immunol 10(12): 849-59.
  187. Ding, Y., J. Xu, et al. (2012). "Regulatory T cell migration during an immune response." Trends Immunol 33(4): 174-80.
  188. Yoshihisa, Y. and T. Shimizu "Metal allergy and systemic contact dermatitis: an overview." Dermatol Res Pract 2012: 749561.
  189. Smith, R. J. and G. Aston-Jones (2008). "Noradrenergic transmission in the extended amyg- dala: role in increased drug-seeking and relapse during protracted drug abstinence." Brain Struct Funct 213(1-2): 43-61.
  190. Trautmann, A., M. Akdis, et al. (2000). "T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis." J Clin Invest 106(1): 25-35.
  191. Akkoc, T., P. J. de Koning, et al. (2008). "Increased activation-induced cell death of high IFN-gamma-producing T(H)1 cells as a mechanism of T(H)2 predominance in atopic diseases." J Allergy Clin Immunol 121(3): 652-658 e1.
  192. Altmeyer, M., M. Barthel, et al. "Absence of poly(ADP-ribose) polymerase 1 delays the onset of Salmonella enterica serovar Typhimurium-induced gut inflammation." Infect Immun 78(8): 3420-31.
  193. Akkoc, T., M. Akdis, et al. "Update in the mechanisms of allergen-specific immunotheraphy." Allergy Asthma Immunol Res 3(1): 11-20.
  194. Stock, P., C. Rolinck-Werninghaus, et al. (2007). "The role of anti-IgE therapy in combina- tion with allergen specific immunotherapy for seasonal allergic rhinitis." BioDrugs 21(6): 403-10.
  195. Cruse, H., C. Bartling, et al. (1995). "A modular artificial neural net for controlling a six- legged walking system." Biol Cybern 72(5): 421-30.

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