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Immunotoxicity Testing pp 39–51Cite as

Risk of Autoimmune Disease: Challenges for Immunotoxicity Testing

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Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 598))

Abstract

Autoimmunity represents a potentially diverse and complex category among the range of adverse outcomes for detection with immunotoxicity testing. For this reason, the risk of autoimmune disease is discussed in this overview chapter with additional mention among the later specific protocol chapters. Improvements in clinical diagnostic capabilities and disease recognition have led to a more accurate picture of the extent of autoimmune diseases across different human populations. While the risk of any single autoimmune disease remains modest when compared with that of lung or heart disease, the cumulative prevalence of autoimmune diseases is both significant and increasing. Autoimmune diseases are usually viewed in the context of the damaged tissue or organ (e.g., as a thyroid, gastrointestinal, cardiovascular or neurological disease). But improved recognition that underlying immune dysfunction can connect the risks for these as well as other diseases is critical for optimizing risk assessment. Since autoimmune diseases are chronic in nature with many first appearing in children or in young adults, these diseases exert a serious impact on both health care costs and quality of life. This chapter provides a discussion of the issues that should be considered with immunotoxicity testing for risk of autoimmunity.

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References

  1. Fairweather D, Frisancho-Kiss S, Rose NR (2008) Sex differences in autoimmune disease from a pathological perspective. Am J Pathol 173:600–609

    Article  CAS  PubMed  Google Scholar 

  2. The Autoimmune Disease Coordinating Committee of the National Institutes of Health (2005) Report to Congress, March. NIH Publication No. 05–5140

    Google Scholar 

  3. Shoenfeld Y, Selmi C, Zimlichman E, Gershwin ME (2008) The autoimmunologist: geoepidemiology, a new center of gravity, and prime time for autoimmunity. J Autoimmun 31:325–330

    Article  PubMed  Google Scholar 

  4. Dietert RD, Piepenbrink MS (2008) The managed immune system: protecting the womb to delay the tomb. Hum Exp Toxicol 27:129–134

    Article  PubMed  Google Scholar 

  5. Dietert RR, Zelikoff JT (2009) Pediatric immune dysfunction and health risks following early-life immune insult. Curr Pediatr Rev 5(1):36–51

    Article  CAS  Google Scholar 

  6. Abedi-Valugerdi M (2009) Mercury and silver induce B cell activation and anti-nucleolar autoantibody production in outbred mouse stocks: are environmental factors more important than the susceptibility genes in connection with autoimmunity? Clin Exp Immunol 155:117–124

    Article  CAS  PubMed  Google Scholar 

  7. Cooper GS, Miller FW (2008) Environmental influences on autoimmunity and autoimmune disease. In: Luebke R, House R, Kimber I (eds) Immunotoxicology and immunopharmacology, 3rd edn. CRC Press, Boca Raton, FL, pp 437–453

    Google Scholar 

  8. Silbergeld EK, Silva IA, Nyland JF (2005) Mercury and autoimmunity: implications for occupational and environmental health. Toxicol Appl Pharmacol 207:282–292

    Article  PubMed  Google Scholar 

  9. Havarinasab S, Bjorn E, Ekstrand J, Hultman P (2007) Dose and Hg species determine the T-helper cell activation in murine autoimmunity. Toxicology 229:23–32

    Article  CAS  PubMed  Google Scholar 

  10. Pilones K, Lai ZW, Gavalchan J (2007) Prenatal HgCl(2) exposure alters fetal cell phenotypes. J Immunotoxicol 4:295–301

    Article  CAS  PubMed  Google Scholar 

  11. Bunn TL, Marsh JA, Dietert RR (2000) Gender differences in developmental immunotoxicity to lead in the chicken: analysis following a single early low-level exposure in ovo. J Toxicol Environ Health A 61:677–693

    Article  CAS  PubMed  Google Scholar 

  12. Hudson CA, Cao L, Kasten-Jolly J, Kirkwood JN, Lawrence DA (2003) Susceptibility of lupus-prone NZM mouse strains to lead exacerbation of systemic lupus erythematosus symptoms. J Toxicol Environ Health A 66:895–918

    Article  CAS  PubMed  Google Scholar 

  13. Havarinasab S, Johansson U, Pollard KM, Hultman P (2007) Gold causes genetically determined autoimmune and immunostimulatory responses in mice. Clin Exp Immunol 150:179–188

    Article  CAS  PubMed  Google Scholar 

  14. Blossom SJ, Doss JC (2007) Trichloroethylene alters central and peripheral immune function in autoimmune-prone MRL(+/+) mice following continuous developmental and early life exposure. J Immunotoxicol 4:129–141

    Article  CAS  PubMed  Google Scholar 

  15. Cripps DH, Peters HA, Gocman A, Dogramici I (1984) Porphyria turcica due to hexachlorobenzene: a 20 to 30 year follow-up study on 204 patients. Br J Dermatol 111:412–422

    Article  Google Scholar 

  16. Michielsen CC, van Loveren H, Vos JG (1999) The role of the immune system in hexachlorobenzene-induced toxicity. Environ Health Perspect 107:783–792

    Article  CAS  PubMed  Google Scholar 

  17. Vidali M, Stewart SF, Rolla R, Daly AK, Chen Y, Mottaran E, Jones DE, Leathart JB, Day CP, Albano E (2003) Genetic and epigenetic factors in autoimmune reactions toward cytochrome P4502E1 in alcoholic liver disease. Hepatology 37:410–419

    Article  CAS  PubMed  Google Scholar 

  18. Brown JM, Pfau JC, Pershouse MA, Holian A (2005) Silica, apoptosis, and autoimmunity. J Immunotoxicol 1:177–187

    Article  PubMed  Google Scholar 

  19. Otsuki T, Maeda M, Murakami S, Hayashi H, Miura Y, Kusaka M, Nakano T, Fukuoka K, Kishimoto T, Hyodoh F, Ueki A, Nishimura Y (2007) Immunological effects of silica and asbestos. Cell Mol Immunol 4:261–268

    CAS  PubMed  Google Scholar 

  20. Mustafa A, Holladay SD, Goff M, Witonsky SG, Kerr R, Reilly CM, Sponenberg DP, Roddick GT, Jr M (2008) An enhanced postnatal autoimmune profile in 24 week-old C57BL/6 mice developmentally exposed to TCDD. Toxicol Appl Pharmacol 232:51–59

    Article  CAS  PubMed  Google Scholar 

  21. Zhou Y, Lu Q (2008) DNA methylation in T cells from idiopathic lupus and drug-induced lupus patients. Autoimmun Rev 7:376–383

    Article  CAS  PubMed  Google Scholar 

  22. Barendrecht MM, Tervaert JW, van Breda Vriesman PJ, Damoiseaux JG (2002) Susceptibility to cyclosporin A-induced autoimmunity: strain differences in relation to autoregulatory T cells. J Autoimmun 18:39–48

    Article  PubMed  Google Scholar 

  23. Brix TH, Hansen PS, Kyvik KO, Hegedus L (2000) Cigarette smoking and risk of clinically overt thyroid disease: a population-based twin case-control study. Arch Intern Med 160:661–666

    Article  CAS  PubMed  Google Scholar 

  24. Guilherme L, Fae KC, Oshiro SE, Tanaka AC, Pomerantzeff PM, Kalil J (2007) T cell response in rheumatic fever: crossreactivity between streptococcal M protein peptides and heart tissue proteins. Curr Protein Pept Sci 8:39–44

    Article  CAS  PubMed  Google Scholar 

  25. Cunha-Neto E, Bilate AM, Hyland KV, Fonseen SG, Kalil J, Museum ED, Galleries A (2006) Induction of cardiac autoimmunity in Chagas heart disease: a case for molecular mimicry. Autoimmunity 39:41–54

    Article  CAS  PubMed  Google Scholar 

  26. Rose NR (2008) The adjuvant effect in infection and autoimmunity. Clin Rev Allergy Immunol 34:279–282

    Article  CAS  PubMed  Google Scholar 

  27. Croker BA, Lawson BR, Berger M, Rutschmann S, Berger M, Eidenschenk C, Blasius AL, Moresco EM, Sovath S, Cengia L, Shultz LD, Theofilopoulos AN, Pettersson S, Beutler BA (2008) Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger. Proc Natl Acad Sci USA 105:15028–15033

    Article  CAS  PubMed  Google Scholar 

  28. Rose NR (2008) Autoimmunity in coxsackievirus infection. Curr Top Microbiol Immunol 323:293–314

    Article  CAS  PubMed  Google Scholar 

  29. Larizza D, Calcaterra V, Martinetti M, Negini R, De Silvestri A, Cisternino M, Iannone AM, Solcia E (2006) Helicobacter pylori infection and autoimmune thyroid disease in young patients: the disadvantage of carrying the human leukocyte antigen-DRB1*0301 allele. Clin J Endocrinol Metab 91:176–179

    Article  CAS  Google Scholar 

  30. Vas J, Mattner J, Richardson S, Ndonye R, Gaughan JP, Howell A, Monestier M (2008) Regulatory roles for NKT cell ligands in environmentally induced autoimmunity. J Immunol 181:6779–6788

    CAS  PubMed  Google Scholar 

  31. Cooke A (2009) Infection and autoimmunity. Blood Cells Mol Dis 42:105–107

    Article  CAS  PubMed  Google Scholar 

  32. Mattner J, Savage PB, Peung P, Oertelt SS, Wang V, Trivedi O, Scanlon ST, Pendem K, Teyton L, Hart J, Ridgway WM, Wicker LS, Gershwin ME, Bendelac A (2008) Liver autoimmunity triggered by microbial activation of natural killer T cells. Cell Host Microbe 3:304–315

    Article  CAS  PubMed  Google Scholar 

  33. Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld JC, Stockinger B (2008) The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453:106–109

    Article  CAS  PubMed  Google Scholar 

  34. Ober C, Loisel DA, Gilad Y (2008) Sex-specific genetic architecture of human disease. Nat Rev Genet 9:911–922

    Article  CAS  PubMed  Google Scholar 

  35. Fairweather D, Rose NR (2004) Women and autoimmune diseases. Emerg Infect Dis 10:2005–2011

    CAS  PubMed  Google Scholar 

  36. Calin A, Brophy S, Blake D (1999) Impact of sex on inheritance of ankylosing spondylitis: a cohort study. Lancet 354:1687–1690

    Article  CAS  PubMed  Google Scholar 

  37. World Health Organization. Environmental Health Criteria 236 (2006) Principles and methods for assessing autoimmunity associated with exposure to chemicals. WHO Publications, Geneva, Switzerland

    Google Scholar 

  38. Gleicher N, Barad DH (2007) Gender as risk factor for autoimmune diseases. J Autoimmun 28:1–6

    Article  CAS  PubMed  Google Scholar 

  39. Zandman-Goddard G, Peeva E, Shoenfeld Y (2007) Gender and autoimmunity. Autoimmun Rev 6:366–372

    Article  CAS  PubMed  Google Scholar 

  40. Gause WC, Jackson JV, Dietert RR, Marsh JA (1985) Autoanti-thyroglobulin production in obese chickens: influence of age and sex as measured by ELISA. Dev Comp Immunol 9:107–118

    Article  CAS  PubMed  Google Scholar 

  41. Sorg H, Lorch B, Jaster R, Fitzner B, Ibrahim S, Holzhueter SA, Nizze H, Vollmar B (2009) Early rise in inflammation and microcirculatory disorder determine the development of autoimmune pancreatitis in the MRL/Mp-mouse. Am J Physiol Gastrointest Liver Physiol 295:G1274–G1280

    Article  Google Scholar 

  42. Gubbels Bupp MR, Jorgensen TN, Kotzin B (2008) Identification of candidate genes that influence sex hormone-dependent disease phenotypes in mouse lupus. Genes Immun 9:47–56

    Article  CAS  PubMed  Google Scholar 

  43. Hughes GC, Clark EA (2007) Regulation of dendritic cells by female sex steroids: relevance to immunity and autoimmunity. Autoimmunity 40:470–481

    Article  CAS  PubMed  Google Scholar 

  44. Stevens AM (2006) Microchimeric cells in systemic lupus erythematosus: targets or innocent bystanders? Lupus 15:820–826

    Article  CAS  PubMed  Google Scholar 

  45. Rak JM, Maestroni L, Balandraud N, Guis S, Boudinet H, Guzian MC, Yan Z, Azzouz D, Auger I, Roudier C, Martin M, Didelot R, Roudier J, Lamber NC (2008) Transfer of the shared epitope through microchimerism in women with rheumatoid arthritis. Arthritis Rheum 60:73–80

    Article  Google Scholar 

  46. Selmi C, Invernizzi P, Gershwin ME (2006) The X chromosome and systemic sclerosis. Curr Opin Rheumatol 18:601–605

    Article  PubMed  Google Scholar 

  47. Smith-Bouvier DL, Divekar AA, Sasidhar M, Du S, Tiwari-Woodruff SK, King JK, Arnold AP, Singh RR, Voskuhl RR (2008) A role for sex chromosome complement in the female bias in autoimmune disease. J Exp Med 205:1099–1108

    Article  CAS  PubMed  Google Scholar 

  48. Invernuizzi P, Miozzo M, Oetelt-Prigione S, Meroni PL, Persani L, Selmi C, Battezzati PM, Zuin M, Lucchi S, Marasini B, Zeni S, Watnik M, Tabano S, Maitz S, Pasini S, Gershwin ME, Podda M (2007) X monosomy in female systemic lupus erythematosus. Ann N Y Acad Sci 1110:84–91

    Article  Google Scholar 

  49. Nandula SR, Armarnath S, Molinolo A, Bandyopadhyay BC, Hall B, Goldsmith CM, Zheng C, Larsson J, Sreenath T, Chen W, Ambudkar IS, Karlsson S, Baum BJ, Kulkarni AB (2007) Female mice are more susceptible to developing inflammatory disorders due to impaired transforming growth factor beta signaling in salivary glands. Arthritis Rheum 56:1798–1805

    Article  CAS  PubMed  Google Scholar 

  50. Jane-wit D, Altuntas CZ, Monti J, Johnson JM, Forsthuber TG, Tuohy VK (2008) Sex-defined T-cell responses to cardiac self determine differential outcomes of murine dilated cardiomyopathy. Am J Pathol 172:11–21

    Article  CAS  PubMed  Google Scholar 

  51. Sinha S, Kaler LT, Procter TM, Teuscher C, Vandenbark AA, Offner H (2008) IL-13-mediated gender difference in susceptibility to autoimmune encephalomyelitis. J Immunol 180:2679–2685

    CAS  PubMed  Google Scholar 

  52. Hastings KL (2006) Risk assessment in drug development: autoimmunity. J Toxicol Environ Health A 69:893–898

    Article  CAS  Google Scholar 

  53. Goldstein NS, Bayati N, Silverman AL, Gordon SG (2000) Minocycline as a cause of drug-induced autoimmune hepatitis: report of four cases and comparison with autoimmune hepatitis. Am J Clin Pathol 114:591–598

    Article  CAS  PubMed  Google Scholar 

  54. Chamberlain MC, Schwartzenberg SJ, Akin EU, Kurth MH (2006) Minocycline-induced autoimmune hepatitis with subsequent cirrhosis. J Pediatr Gastroenterol Nutr 42:232–235

    Article  PubMed  Google Scholar 

  55. Schuurs AH, Dietrich H, Gruber J, Wick G (1992) Effects of sex steroid analogs on spontaneous autoimmune thyroiditis in obese strain chickens. Int Arch Allergy Immunol 97:337–344

    Article  CAS  PubMed  Google Scholar 

  56. Lam-Tse WK, Lernmark A, Drexhage HA (2002) Animal models of endocrine/organ-specific autoimmune diseases: do they really help us to understand human autoimmunity? Springer Semin Immunopathol 24:297–321

    Article  CAS  PubMed  Google Scholar 

  57. Morrel L (2004) Mouse models of human autoimmune diseases: essential tools that require the proper controls. PloS Biol 2:e241

    Article  Google Scholar 

  58. Cooper GS, Gilbert KM, Greidlinger EL, James JA, Pfau JC, Reinlib L, Richardson BC, Rose NR (2008) Recent advances and opportunities in research on lupus: environmental influences and mechanism of disease. Environ Health Perspect 116:695–702

    Article  CAS  PubMed  Google Scholar 

  59. Gerosa M, De Angeslis V, Roboldi P, Meroni PL (2008) Rheumatoid arthritis: a female challenge. Womens Health (Lond) 4:195–201

    CAS  Google Scholar 

  60. Lleo A, Battezzati PM, Selmi C, Selmi C, Gershwin ME, Podda M (2008) Is autoimmunity a matter of sex? Autoimmun Rev 7:626–630

    Article  CAS  PubMed  Google Scholar 

  61. Rose NR (2008) Predictors of autoimmune disease: autoantibodies and beyond. Autoimmunity 41:419–428

    Article  CAS  PubMed  Google Scholar 

  62. Plot L, Amiltal H (2009) Infectious associations of Celiac disease. Autoimmun Rev 8(4):316–319

    Article  CAS  PubMed  Google Scholar 

  63. Ercolini AM, Miller SD (2009) The role of infections in autoimmune disease. Clin Exp Immunol 155:1–15

    Article  CAS  PubMed  Google Scholar 

  64. Tabuenca JM (1981) Toxic-allergic syndrome caused by ingestion of rapeseed oil denatured with aniline. Lancet 2:567–568

    CAS  PubMed  Google Scholar 

  65. Noonan CW, Pfau JC, Larson TC, Spence MR (2006) Nested case-control study of autoimmune disease in an asbestos-exposed population. Environ Health Perspect 114:1243–1247

    Article  CAS  PubMed  Google Scholar 

  66. Yurino H, Ishikawa S, Sato T, Akadegawa K, Ito T, Ueha S, Inadera H, Matsushima K (2004) Endocrine disruptors (environmental estrogens) enhance autoantibody production by B1 cells. Toxicol Sci 81:139–147

    Article  CAS  PubMed  Google Scholar 

  67. Costenbader KH, Kim DJ, Peerzada J, Lockman S, Nobles-Knight D, Petri M, Karlson EW (2004) Cigarette smoking and the risk of systemic lupus erythematosus: a meta-analysis. Arthritis Rheum 50:849–857

    Article  PubMed  Google Scholar 

  68. Burke L, Segall-Blank M, Lorenzo C, Dynesius-Trentham R, Trentham D, Mortola JF (2001) Altered immune response in adult women exposed to diethylstilbestrol in utero. Am J Gynecol 185:78–81

    Article  CAS  Google Scholar 

  69. Fenaux JB, Gogal RM Jr, Lindsay D, Hardy C, Ward DL, Saunders G, Ahmed SA (2005) Altered splenocyte function in aged C57BL/6 mice prenatally exposed to diethylstilbestrol. J Immunotoxicol 2:221–229

    Article  CAS  PubMed  Google Scholar 

  70. Grimaldi CM (2006) Sex and systemic lupus erythematosus: the role of the sex hormones estrogen and prolactin on the regulation of autoreactive B cells. Curr Opin Rhematol 18:456–461

    Article  CAS  Google Scholar 

  71. Poole BD, Templeton AK, Guthridge JM, Brown EJ, Harley JB, James JA (2009) Aberrant Epstein-Barr viral infection in systemic lupus erythematosus. Autoimmun Rev 8:337–342

    Article  CAS  PubMed  Google Scholar 

  72. Lunardi C, Tinazzi E, Bason C, Dolcino M, Corrocher R, Puccetti A (2008) Human parvovirus B19 infection and autoimmunity. Autoimmun Rev 8:116–120

    Article  CAS  PubMed  Google Scholar 

  73. Vas J, Monestier M (2008) Immunology of mercury. Ann N Y Acad Sci 1143:240–267

    Article  CAS  PubMed  Google Scholar 

  74. Wang F, Roberts SM, Butfiloski EJ, Morel L, Sobel ES (2007) Acceleration of autoimmunity by organochlorine pesticides: a comparison of splenic B-cell effects of chlordecone and estradiol in (NZBxNZW)F1 mice. Toxicol Sci 99:141–152

    Article  CAS  PubMed  Google Scholar 

  75. Tsai PC, Ko YC, Huang W, Liu HS, Guo YL (2007) Increased liver and lupus mortalities in 24-year follow-up of the Taiwanese people highly exposed to polychlorinated biphenyls and dibenzofurans. Sci Total Environ 374:216–222

    Article  CAS  PubMed  Google Scholar 

  76. Jara LJ, Benitez G, Medina G (2008) Prolactin, dendritic cells, and systemic lupus erythematosus. Autoimmun Rev 7:251–255

    Article  CAS  PubMed  Google Scholar 

  77. Parks CG, Cooper GS, Nylander-French LA et al (2002) Occupational exposure to crystalline silica and risk of systemic lupus erythematosus: a population-based, case-control study in the southeastern United States. Arthritis Rheum 46:1840–1850

    Article  PubMed  Google Scholar 

  78. Menke J, Hsu MY, Byrne KT, Lucas JA, Rabacal WA, Croker BP, Zong XH, Stanley ER, Kelley VR (2008) Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice. J Immunol 181:7367–7379

    CAS  PubMed  Google Scholar 

  79. Cai P, König R, Boor PJ, Kondraganti S, Kaphalia BS, Khan MF, Ansari GA (2008) Chronic exposure to trichloroethylene causes early onset of SLE-like disease in female MRL +/+ mice. Toxicol Appl Pharmacol 228:68–75

    Article  CAS  PubMed  Google Scholar 

  80. Eidson M, Philen RM, Sewell CM, Voorhees R, Kilbourne EM (1990) L-Tryptophan and eosinophilia-myalgia syndrome in New Mexico. Lancet 335:645–648

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA

    Rodney R. Dietert

  2. Department of Microbiology and Immunology, Performance Plus Consulting, Lansing, NY, USA

    Janice M. Dietert

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  1. Rodney R. Dietert
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  1. College of Veterinary Medicine, Cornell University, Ithaca, 14853, U.S.A.

    Rodney R. Dietert

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Dietert, R.R., Dietert, J.M., Gavalchin, J. (2010). Risk of Autoimmune Disease: Challenges for Immunotoxicity Testing. In: Dietert, R. (eds) Immunotoxicity Testing. Methods in Molecular Biology™, vol 598. Humana Press. https://doi.org/10.1007/978-1-60761-401-2_4

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