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Pathological Analysis of Metal Allergy to Metallic Materials

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Advances in Metallic Biomaterials

Part of the book series: Springer Series in Biomaterials Science and Engineering ((SSBSE,volume 3))

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Abstract

Metal allergy is thought to be caused by the release of ions from metallic materials. Extensive use of metal in jewelry, coins, surgical instruments, and dental restorations may be responsible for recent increases in allergy incidence. Metal allergic disease is categorized as a delayed-type hypersensitivity, which is developed more than 24 h after exposure to the causal metal. The hallmark of delayed-type hypersensitivity is the recruitment of lymphocytes and inflammatory cells, including T cells and granulocytes, to the site of allergic inflammation. During the development of metal allergy, T cells are known to play a role, and since metal ions are thought to function as haptens, T cell-mediated responses likely contribute to allergic disease. While the involvement of pathogenic T cells in the development of metal allergy has not been explored using animal models, studies utilizing human patient samples have been conducted. T cell clones, both CD4+ and CD8+, have been established from peripheral blood mononuclear cells of patients with metal allergy, and their responsiveness to the causal metal has been analyzed. It was found that metal ions induced proliferation of these T cells in vitro and some of the T cell clones produced IFN-γ or IL-4 after metal stimulation, while others produced both T helper 1- and 2-type cytokines. However, the subset of pathogenic T cells involved in the development of metal allergy and their cytokine profiles remain controversial. Recently, a novel animal model that reproduces human metal allergy has been established. Here we show the pathogenesis of metal allergy in the view of immunological responses using this animal model.

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References

  1. Bendiner E (1981) Baron von Pirquet: the aristocrat who discovered and defined allergy. Hosp Pract (Off Ed) 16:137, 141, 144 passim

    Google Scholar 

  2. Rajan TV (2003) The Gell-Coombs classification of hypersensitivity reactions: a re-interpretation. Trends Immunol 24:376–379

    Article  Google Scholar 

  3. Gell PGH, Coombs RRA (1963) The classification of allergic reactions underlying disease. In: Coombs RRA, Gells PGH (eds) Clinical aspects of immunology. Blackwell, Oxford

    Google Scholar 

  4. Saint-Mezard P, Rosieres A, Krasteva M, Berard F, Dubois B et al (2004) Allergic contact dermatitis. Eur J Dermatol 14:284–295

    Google Scholar 

  5. Krasteva M, Kehren J, Sayag M, Ducluzeau MT, Dupuis M et al (1999) Contact dermatitis II. Clinical aspects and diagnosis. Eur J Dermatol 9:144–159

    Google Scholar 

  6. Nosbaum A, Vocanson M, Rozieres A, Hennino A, Nicolas JF (2009) Allergic and irritant contact dermatitis. Eur J Dermatol 19:325–332

    Google Scholar 

  7. Mortz CG, Andersen KE (1999) Allergic contact dermatitis in children and adolescents. Contact Dermatitis 41:121–130

    Article  Google Scholar 

  8. Onder M, Adisen E (2008) Patch test results in a Turkish paediatric population. Contact Dermatitis 58:63–65

    Article  Google Scholar 

  9. Brandão MH, Gontijo B (2012) Contact sensitivity to metals (chromium, cobalt and nickel) in childhood. An Bras Dermatol 87:269–276

    Google Scholar 

  10. Schäfer T, Böhler E, Ruhdorfer S, Weigl L, Wessner D et al (2001) Epidemiology of contact allergy in adults. Allergy 56:1192–1196

    Article  Google Scholar 

  11. Rietschel RL, Fowler JFJ (2008) Metals. BC Decker Inc., Hamilton

    Google Scholar 

  12. Ostendrop P (2001) Nickel: hidden in plain sight. Dartmouth.edu [Internet].

    Google Scholar 

  13. Kornik R, Zug KA (2008) Nickel. Dermatitis 19:3–8

    Google Scholar 

  14. Thyssen JP, Johansen JD, Menné T (2007) Contact allergy epidemics and their controls. Contact Dermatitis 56:185–195

    Article  Google Scholar 

  15. Vozmediano JM, Hita JCA (2005) Allergic contact dermatitis in children. J Eur Acad Dermatol Venerol 19(1):42–46

    Article  Google Scholar 

  16. Thyssen JP, Menné T (2010) Metal allergy – a review on exposures, penetration, genetics, prevalence, and clinical implications. Chem Res Toxicol 23:309–318

    Article  Google Scholar 

  17. Ekqvist S, Svedman C, Möller H, Kehler M, Pripp CM et al (2007) High frequency of contact allergy to gold in patients with endovascular coronary stents. Br J Dermatol 157:730–738

    Article  Google Scholar 

  18. Hostynek JJ (2003) Factors determining percutaneous metal absorption. Food Chem Toxicol 41:327–345

    Article  Google Scholar 

  19. Larese F, Gianpietro A, Venier M, Maina G, Renzi N (2007) In vitro percutaneous absorption of metal compounds. Toxicol Lett 170:49–56

    Article  Google Scholar 

  20. Cavani A, De Pità O, Girolomoni G (2007) New aspects of the molecular basis of contact allergy. Curr Opin Allergy Clin Immunol 7:404–408

    Article  Google Scholar 

  21. Gamerdinger K, Moulon C, Karp DR, Van Bergen J, Koning F et al (2003) A new type of metal recognition by human T cells: contact residues for peptide-independent bridging of T cell receptor and major histocompatibility complex by nickel. J Exp Med 197:1345–1353

    Article  Google Scholar 

  22. Nielsen NH, Linneberg A, Menné T, Madsen F, Frølund L et al (2001) Persistence of contact allergy among Danish adults: an 8-year follow-up study. Contact Dermatitis 45:350–353

    Article  Google Scholar 

  23. Andersen KE, Johansen JD, Bruze M, Frosch PJ, Goossens A et al (2001) The time-dose-response relationship for elicitation of contact dermatitis in isoeugenol allergic individuals. Toxicol Appl Pharmacol 170:166–171

    Article  Google Scholar 

  24. Hextall JM, Alagaratnam NJ, Glendinning AK, Holloway DB, Blaikie L et al (2002) Dose-time relationships for elicitation of contact allergy to para-phenylenediamine. Contact Dermatitis 47:96–99

    Article  Google Scholar 

  25. Agner T, Johansen JD, Overgaard L, Vølund A, Basketter D et al (2002) Combined effects of irritants and allergens. Synergistic effects of nickel and sodium lauryl sulfate in nickel-sensitized individuals. Contact Dermatitis 47:21–26

    Article  Google Scholar 

  26. Kaplan DH, Igyártó BZ, Gaspari AA (2012) Early immune events in the induction of allergic contact dermatitis. Nat Rev Immunol 12:114–124

    Google Scholar 

  27. Förster R, Schubel A, Breitfeld D, Kremmer E, Renner-Müller I et al (1999) CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99:23–33

    Article  Google Scholar 

  28. Itano AA, McSorley SJ, Reinhardt RL, Ehst BD, Ingulli E et al (2003) Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. Immunity 19:47–57

    Article  Google Scholar 

  29. Allenspach EJ, Lemos MP, Porrett PM, Turka LA, Laufer TM (2008) Migratory and lymphoid-resident dendritic cells cooperate to efficiently prime naive CD4 T cells. Immunity 29:795–806

    Article  Google Scholar 

  30. Ohl L, Mohaupt M, Czeloth N, Hintzen G, Kiafard Z et al (2004) CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 21:279–288

    Article  Google Scholar 

  31. Balato A, Balato N, Di Costanzo L, Ayala F (2011) Contact sensitization in the elderly. Clin Dermatol 29:24–30

    Article  Google Scholar 

  32. Saint-Mezard P, Krasteva M, Chavagnac C, Bosset S, Akiba H et al (2003) Afferent and efferent phases of allergic contact dermatitis (ACD) can be induced after a single skin contact with haptens: evidence using a mouse model of primary ACD. J Invest Dermatol 120:641–647

    Article  Google Scholar 

  33. Lidén C, Norberg K (2005) Nickel on the Swedish market. Follow-up after implementation of the Nickel Directive. Contact Dermatitis 52:29–35

    Article  Google Scholar 

  34. Kaaber K, Veien NK, Tjell JC (1978) Low nickel diet in the treatment of patients with chronic nickel dermatitis. Br J Dermatol 98:197–201

    Article  Google Scholar 

  35. Veien NK (2011) Systemic contact dermatitis. Int J Dermatol 50:1445–1456

    Article  Google Scholar 

  36. Hsu JW, Matiz C, Jacob SE (2011) Nickel allergy: localized, id, and systemic manifestations in children. Pediatr Dermatol 28:276–280

    Article  Google Scholar 

  37. Veien NK, Hattel T, Laurberg G (1995) Placebo-controlled oral challenge with cobalt in patients with positive patch tests to cobalt. Contact Dermatitis 33:54–55

    Article  Google Scholar 

  38. Asano Y, Makino T, Norisugi O, Shimizu T (2009) Occupational cobalt induced systemic contact dermatitis. Eur J Dermatol 19:166–167

    Google Scholar 

  39. Stuckert J, Nedorost S (2008) Low-cobalt diet for dyshidrotic eczema patients. Contact Dermatitis 59:361–365

    Article  Google Scholar 

  40. Romero-Brufau S, Best PJ, Holmes DR, Mathew V, Davis MD et al (2012) Outcomes after coronary stent implantation in patients with metal allergy. Circ Cardiovasc Interv 5:220–226

    Article  Google Scholar 

  41. Hansen MB, Johansen JD, Menné T (2003) Chromium allergy: significance of both Cr(III) and Cr(VI). Contact Dermatitis 49:206–212

    Article  Google Scholar 

  42. Yoshihisa Y, Shimizu T (2012) Metal allergy and systemic contact dermatitis: an overview. Dermatol Res Pract 2012:749561

    Google Scholar 

  43. Kaaber K, Veien NK (1977) The significance of chromate ingestion in patients allergic to chromate. Acta Derm Venereol 57:321–323

    Google Scholar 

  44. Veien NK, Hattel T, Laurberg G (1994) Chromate-allergic patients challenged orally with potassium dichromate. Contact Dermatitis 31:137–139

    Article  Google Scholar 

  45. Gao X, He RX, Yan SG, Wu LD (2011) Dermatitis associated with chromium following total knee arthroplasty. J Arthroplasty 26:665.e613–666

    Article  Google Scholar 

  46. Merad M, Manz MG, Karsunky H, Wagers A, Peters W et al (2002) Langerhans cells renew in the skin throughout life under steady-state conditions. Nat Immunol 3:1135–1141

    Article  Google Scholar 

  47. Faurschou A, Menné T, Johansen JD, Thyssen JP (2011) Metal allergen of the 21st century – a review on exposure, epidemiology and clinical manifestations of palladium allergy. Contact Dermatitis 64:185–195

    Article  Google Scholar 

  48. Larese Filon F, Uderzo D, Bagnato E (2003) Sensitization to palladium chloride: a 10-year evaluation. Am J Contact Dermat 14:78–81

    Article  Google Scholar 

  49. Hindsén M, Spirén A, Bruze M (2005) Cross-reactivity between nickel and palladium demonstrated by systemic administration of nickel. Contact Dermatitis 53:2–8

    Article  Google Scholar 

  50. Goodacre CJ (1989) Palladium-silver alloys: a review of the literature. J Prosthet Dent 62:34–37

    Article  Google Scholar 

  51. Rebandel P, Rudzki E (1990) Allergy to palladium. Contact Dermatitis 23:121–122

    Article  Google Scholar 

  52. Hackel H, Miller K, Elsner P, Burg G (1991) Unusual combined sensitization to palladium and other metals. Contact Dermatitis 24:131–132

    Article  Google Scholar 

  53. Möller H, Ohlsson K, Linder C, Björkner B, Bruze M (1999) The flare-up reactions after systemic provocation in contact allergy to nickel and gold. Contact Dermatitis 40:200–204

    Article  Google Scholar 

  54. Möller H, Björkner B, Bruze M, Lundqvist K, Wollmer P (1999) Laser Doppler perfusion imaging for the documentation of flare-up in contact allergy to gold. Contact Dermatitis 41:131–135

    Article  Google Scholar 

  55. Summer B, Paul C, Mazoochian F, Rau C, Thomsen M et al (2010) Nickel (Ni) allergic patients with complications to Ni containing joint replacement show preferential IL-17 type reactivity to Ni. Contact Dermatitis 63:15–22

    Article  Google Scholar 

  56. Hashizume H, Seo N, Ito T, Takigawa M, Yagi H (2008) Promiscuous interaction between gold-specific T cells and APCs in gold allergy. J Immunol 181:8096–8102

    Article  Google Scholar 

  57. de Vos G, Abotaga S, Liao Z, Jerschow E, Rosenstreich D (2007) Selective effect of mercury on Th2-type cytokine production in humans. Immunopharmacol Immunotoxicol 29:537–548

    Article  Google Scholar 

  58. Pennino D, Eyerich K, Scarponi C, Carbone T, Eyerich S et al (2010) IL-17 amplifies human contact hypersensitivity by licensing hapten nonspecific Th1 cells to kill autologous keratinocytes. J Immunol 184:4880–4888

    Article  Google Scholar 

  59. Minang JT, Areström I, Troye-Blomberg M, Lundeberg L, Ahlborg N (2006) Nickel, cobalt, chromium, palladium and gold induce a mixed Th1- and Th2-type cytokine response in vitro in subjects with contact allergy to the respective metals. Clin Exp Immunol 146:417–426

    Article  Google Scholar 

  60. Budinger L, Neuser N, Totzke U, Merk HF, Hertl M (2001) Preferential usage of TCR-Vbeta17 by peripheral and cutaneous T cells in nickel-induced contact dermatitis. J Immunol 167:6038–6044

    Article  Google Scholar 

  61. Silvennoinen-Kassinen S, Karvonen J, Ikaheimo I (1998) Restricted and individual usage of T-cell receptor beta-gene variables in nickel-induced CD4+ and CD8+ cells. Scand J Immunol 48:99–102

    Article  Google Scholar 

  62. Peiser M, Tralau T, Heidler J, Api AM, Arts JH et al (2012) Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects. Current knowledge assembled at an international workshop at BfR, Germany. Cell Mol Life Sci 69:763–781

    Article  Google Scholar 

  63. Honda T, Egawa G, Grabbe S, Kabashima K (2013) Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis. J Invest Dermatol 133:303–315

    Article  Google Scholar 

  64. Lepoittevin JP, Karlberg AT (1994) Interactions of allergenic hydroperoxides with proteins: a radical mechanism? Chem Res Toxicol 7:130–133

    Article  Google Scholar 

  65. Lepoittevin JP (2006) Metabolism versus chemical transformation or pro-versus prehaptens? Contact Dermatitis 54:73–74

    Article  Google Scholar 

  66. Martin SF, Esser PR, Weber FC, Jakob T, Freudenberg MA et al (2011) Mechanisms of chemical-induced innate immunity in allergic contact dermatitis. Allergy 66:1152–1163

    Article  Google Scholar 

  67. Schmidt M, Raghavan B, Müller V, Vogl T, Fejer G et al (2010) Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. Nat Immunol 11:814–819

    Article  Google Scholar 

  68. Kawano M, Nakayama M, Aoshima Y, Nakamura K, Ono M et al (2014) NKG2D+ IFN-gamma+ CD8+ T cells are responsible for palladium allergy. PLoS One 9(2):e86810

    Article  Google Scholar 

  69. Eguchi T, Kumagai K, Kobayashi H, Shigematsu H, Kitaura K et al (2013) Accumulation of invariant NKT cells into inflamed skin in a novel murine model of nickel allergy. Cell Immunol 284:163–171

    Article  Google Scholar 

  70. Kobayashi H, Kumagai K, Eguchi T, Shigematsu H, Kitaura K et al (2013) Characterization of T cell receptors of Th1 cells infiltrating inflamed skin of a novel murine model of palladium-induced metal allergy. PLoS One 8:e76385

    Article  Google Scholar 

  71. Bour H, Peyron E, Gaucherand M, Garrigue JL, Desvignes C et al (1995) Major histocompatibility complex class I-restricted CD8+ T cells and class II-restricted CD4+ T cells, respectively, mediate and regulate contact sensitivity to dinitrofluorobenzene. Eur J Immunol 25:3006–3010

    Article  Google Scholar 

  72. Wong SC, Tan AH, Lam KP (2009) Functional hierarchy and relative contribution of the CD28/B7 and ICOS/B7-H2 costimulatory pathways to T cell-mediated delayed-type hypersensitivity. Cell Immunol 256:64–71

    Article  Google Scholar 

  73. Warnecke G, Chapman SJ, Bushell A, Hernandez-Fuentes M, Wood KJ (2007) Dependency of the trans vivo delayed type hypersensitivity response on the action of regulatory T cells: implications for monitoring transplant tolerance. Transplantation 84:392–399

    Article  Google Scholar 

  74. Friedmann-Morvinski D, Bendavid A, Waks T, Schindler D, Eshhar Z (2005) Redirected primary T cells harboring a chimeric receptor require costimulation for their antigen-specific activation. Blood 105:3087–3093

    Article  Google Scholar 

  75. Hazlett LD, McClellan S, Barrett R, Rudner X (2001) B7/CD28 costimulation is critical in susceptibility to Pseudomonas aeruginosa corneal infection: a comparative study using monoclonal antibody blockade and CD28-deficient mice. J Immunol 166:1292–1299

    Article  Google Scholar 

  76. Cerwenka A, Lanier LL (2001) Ligands for natural killer cell receptors: redundancy or specificity. Immunol Rev 181:158–169

    Article  Google Scholar 

  77. Diefenbach A, Tomasello E, Lucas M, Jamieson AM, Hsia JK et al (2002) Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D. Nat Immunol 3:1142–1149

    Article  Google Scholar 

  78. Wu J, Song Y, Bakker AB, Bauer S, Spies T et al (1999) An activating immunoreceptor complex formed by NKG2D and DAP10. Science 285:730–732

    Article  Google Scholar 

  79. Thierse HJ, Gamerdinger K, Junkes C, Guerreiro N, Weltzien HU (2005) T cell receptor (TCR) interaction with haptens: metal ions as non-classical haptens. Toxicology 209:101–107

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan

    Mitsuko Kawano, Yuri Takeda & Kouetsu Ogasawara

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  1. Mitsuko Kawano
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  2. Yuri Takeda
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  3. Kouetsu Ogasawara
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Correspondence to Kouetsu Ogasawara .

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Editors and Affiliations

  1. Institute for Materials Research, Tohoku University, Sendai, Japan

    Mitsuo Niinomi

  2. Department of Materials Processing, Tohoku University, Sendai, Japan

    Takayuki Narushima

  3. Institute for Materials Research, Tohoku University, Sendai, Japan

    Masaaki Nakai

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Kawano, M., Takeda, Y., Ogasawara, K. (2015). Pathological Analysis of Metal Allergy to Metallic Materials. In: Niinomi, M., Narushima, T., Nakai, M. (eds) Advances in Metallic Biomaterials. Springer Series in Biomaterials Science and Engineering, vol 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46836-4_13

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