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Pharmacology of Immunotherapeutic Drugs pp 207–249Cite as

Mechanisms of Autoimmunity and Pharmacologic Treatments

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Abstract

Autoimmune disease is thought to affect more than 5% of the world’s population, and thus represents a significant healthcare burden. Autoimmunity results from an inappropriate immune response to self-antigens (also called autoantigens), which results in inflammation and subsequent tissue damage. Depending on the autoantigen targeted, tissue damage from this destructive attack by the immune system can be organ-specific or systemic in nature. Causative mechanisms tipping the scales toward immune attack against self include a combination of genetic and environmental factors, as well as a failure of immune regulation. The mechanisms of several autoimmune disorders, including rheumatoid arthritis and systemic lupus erythematosus are discussed here. Additionally, immune system drug targets are also described as treatments for these autoimmune disorders in which immunosuppression is warranted. Many of these drugs are immunomodulatory in nature, suppress one or several pro-inflammatory cytokines, or suppress specific T or B cell activation mechanisms.

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Suggested Reading

  • Amano Y, Lee SW, Allison AC. Inhibition by glucocorticoids of the formation of interleukin-1 alpha, interleukin-1 beta, and interleukin 6: mediation by decreased mRNA stability. Mol Pharmacol. 1993;43:176–82.

    CAS  PubMed  Google Scholar 

  • Barnes PJ, Adock IM. Glucocorticoid resistance in inflammatory diseases. Lancet. 2009;373:1905–17.

    Article  CAS  PubMed  Google Scholar 

  • Berrebi D, Bruscoli S, Cohen N, Foussat A, Migliorati G, Bouchet-Delbos L, Maillot MC, Portier A, Couderc J, Galanaud P, Peuchmaur M, Riccardi C, Emilie D. Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10. Blood. 2003;101:729–38.

    Article  CAS  PubMed  Google Scholar 

  • Boyapati R, Satsangi J, Ho GT. Pathogenesis of Crohn’s disease. F1000 Prime Rep. 2015;7:44.

    Article  CAS  Google Scholar 

  • Bresson D, von Herrath M. Mechanisms underlying type 1 diabetes. Drug Discovery Today Dis Mech. 2004;1(4):321–7.

    Article  CAS  Google Scholar 

  • Brian J. From cancer to rheumatoid arthritis treatment: the story of methotrexate. Pharm J. 2012.

    Google Scholar 

  • Cheung TT, McInnes IB. Future therapeutic targets in rheumatoid arthritis? Semin Immunopathol. 2017;39(4):487–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi J, Kim ST, Craft J. The pathogenesis of systemic lupus erythematosus-an update. Curr Opin Immunol. 2012;24(6):651–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corthay A. How do regulatory T cells work? Scan J Immunol. 2009;70(4):326–36.

    Article  CAS  Google Scholar 

  • Couser WG. Pathogenesis and treatment of glomerulonephritis—an update. J Bras Nefrol. 2016;38(1):107–22.

    Article  PubMed  Google Scholar 

  • Cruz da Silva J, Mariz HA, da Rocha LF, de Oliveira PS, Dantas AT, Duarte AL, et al. Hydroxychloroquine decreased Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients. Clinics (Sao Paulo). 2013;68(6):766–71.

    Article  Google Scholar 

  • Dierickx D, Kentos A, Delannoy A. The role of rituximab in adults with warm antibody autoimmune hemolytic anemia. Blood. 2015;15:3223–9.

    Article  CAS  Google Scholar 

  • Dong C. Targeting Th17 cells in immune disease. Cell Res. 2014;24:901–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farrell RJ, Kelleher D. Glucocorticoid resistance in inflammatory bowel disease. J Endocrinol. 2003;178:339–46.

    Article  CAS  PubMed  Google Scholar 

  • Fasching P, Stradner M, Graninger W, Dejaco C, Fessler J. Therapeutic potential of targeting the Th17/Treg axis in autoimmune disorders. Molecules. 2017;22(1):E134.

    Article  PubMed  CAS  Google Scholar 

  • Fox R. Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum. 1993;2(1):82–91.

    Article  Google Scholar 

  • Ge WS, Fan JG. Integrin antagonists are effective and safe for Crohn’s disease: a meta-analysis. World J Gastroenterol. 2015;21(15):4744–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gracia-Tello B, Ezeonyeji A, Isenberg D. The use of rituximab in newly-diagnosed patients with systemic lupus erythematosus: long-term steroid-saving capacity and clinical effectiveness. Lupus Sci Med. 2017;4(1):e000182.

    Article  PubMed  PubMed Central  Google Scholar 

  • Haanstra KG, Hofman SO, Lopes Estêvão DM, Blezer EL, Bauer J, Yang LL, et al. Antagonizing the α4β1 integrin, but not α4β7, inhibits leukocytic infiltration of the central nervous system in rhesus monkey experimental autoimmune encephalomyelitis. J Immunol. 2013;190(5):1961–73.

    Article  CAS  PubMed  Google Scholar 

  • Howard JF. Myasthenia gravis: a manual for the health care provider. St. Paul, MN: Myasthenia Gravis Foundation of America; 2008.

    Google Scholar 

  • Huennekens FM. The methotrexate story: a paradigm for development of chemotherapeutic agents. Adv Enzym Regul. 1994;34:397–419.

    Article  CAS  Google Scholar 

  • Kuhn A, Bonsmann G, Anders HJ, Herzer P, Tenbrock K, Schneider M. The diagnosis and treatment of systemic lupus erythematosus. Dtsch Arztebl Int. 2015;112:423–32.

    PubMed  PubMed Central  Google Scholar 

  • Ledford H. Drug companies flock to supercharged T-cells in fight against autoimmune disease. Nature. 2017.

    Google Scholar 

  • Mclean LP, Shea-Donohue T, Cross RK. Vedolizumab for the treatment of ulcerative colitis and Crohn’s disease. Immunotherapy. 2012;4(9):883–98.

    Article  CAS  PubMed  Google Scholar 

  • Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 2012;122(4):143–59.

    Article  CAS  Google Scholar 

  • Mittelstadt PR, Ashwell JF. Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ. J Biol Chem. 2001;276:29603–10.

    Article  CAS  PubMed  Google Scholar 

  • Montalban X, Gold R, Thompson AJ, Otero-Romero S, Amato MP, Chandraratna D, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler. 2018;24(2):96–120.

    Article  PubMed  Google Scholar 

  • Neurath M. Thiopurines in IBD. Gastroenterol Hepatol (NY). 2010;6(7):435–6.

    Google Scholar 

  • Packman CH. The clinical pictures of autoimmune hemolytic anemia. Transfus Med Hemother. 2015;42:317–24.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pedersen J, Coskun M, Soendergaard C, Salem M, Nielsen OH. Inflammatory pathways of importance for management of inflammatory bowel disease. World J Gastroenterol. 2014;20(1):64–77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Phillips WD, Vincent A. Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms. F1000Res. 2016;5:F1000 Faculty Rev-1513.

    Article  CAS  Google Scholar 

  • Ray S, Santhalia N, Kundu S, Ganguly S. Autoimmune disorders: an overview of molecular and cellular basis in today’s perspective. J Clin Cell Immunol. 2012;S10:003.

    Google Scholar 

  • Sanders DB, Wolfe GI, Narayanaswami P. Author response: international consensus guidance for management of myasthenia gravis: executive summary. Neurology. 2017;88(5):505–6.

    Article  PubMed  Google Scholar 

  • Singh N, Rieder MJ, Tucker MJ. Mechanisms of glucocorticoid-mediated anti-inflammatory and immunosuppressive action. Pediatr Perinat Drug Therapy. 2004;6:107–15.

    CAS  Google Scholar 

  • Singh JA, Saag KG, Bridges SL, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthr Rheumatol. 2015;68(1):1–26.

    Google Scholar 

  • Song YW, Kang EH. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. QJM. 2010;103(3):139–46.

    Article  CAS  PubMed  Google Scholar 

  • Srivastava A. Belimumab in SLE. Indian J Dermatol. 2016;61(5):550–3.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sussman J, Farrugia ME, Maddison P, Hill M, Leite MI, Hilton-Jones D. Myasthenia gravis: Association of British Neurologists’ management guidelines. Pract Neurol. 2015;15(3):199–206.

    Article  PubMed  Google Scholar 

  • Szollosi DE, Manzoor MK, Aquilato A, Jackson PB, Ghoneim O, Edafiogho IO. Current and novel anti-inflammatory drug targets for inhibition of cytokines and leucocyte recruitment in rheumatic diseases. J Pharm Pharmacol. 2018;70(1):18–26.

    Article  CAS  PubMed  Google Scholar 

  • Taylor PC, Keystone EC, van der Heijde D, Weinblatt ME, del Carmen Morales L, Gonzaga JR, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376:652–62.

    Article  CAS  PubMed  Google Scholar 

  • Tobler A, Meier R, Seitz M, Dewald B, Baggiolini M, Fey M. Glucocorticoids downregulate gene expression of GM-CSF NAP1/IL-8, and IL-6, but no M-CSF in human fibroblasts. Blood. 1992;79:45–51.

    Article  CAS  PubMed  Google Scholar 

  • Tullman MJ. Overview of the epidemiology, diagnosis, and disease progression associated with multiple sclerosis. Am J Manag Care. 2013;19(2 Suppl):S15–20.

    PubMed  Google Scholar 

  • Wahl K, Schuna A. Chapter 91. Rheumatoid arthritis. In: Pharmacotherapy: a pathophysiologic approach. 10th ed. New York: McGraw Hill Education; 2017.

    Google Scholar 

  • Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ. 2003;10(1):45–65.

    Article  CAS  PubMed  Google Scholar 

  • Weinblatt ME. Methotrexate in rheumatoid arthritis: a quarter century of development. Trans Am Clin Climatol Assoc. 2013;124:16–25.

    PubMed  PubMed Central  Google Scholar 

  • Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology. 2004;43(3):267–71.

    Article  CAS  PubMed  Google Scholar 

  • Wu GF, Alvarez E. The immuno-pathophysiology of multiple sclerosis. Neurol Clin. 2011;29(2):257–78.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zenella A, Barcellini W. Treatment of autoimmune hemolytic anemias. Haematologica. 2014;99(10):1547–54.

    Article  CAS  Google Scholar 

  • Zhang J-M, An J. Cytokines, inflammation and pain. Int Anesthesiol Clin. 2007;45(2):27–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zufferey A, Kapur R, Semple JW. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med. 2017;6(2):E16.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy and Physician Assistant Studies, University of Saint Joseph, Hartford, CT, USA

    Doreen E. Szollosi

  2. School of Pharmacy and Physician Assistant Studies, University of Saint Joseph, Hartford, CT, USA

    Mohammed K. Manzoor

  3. Bryant University, Smithfield, RI, USA

    Kirsten Hokeness

Authors
  1. Doreen E. Szollosi
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  2. Kirsten Hokeness
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  3. Mohammed K. Manzoor
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Corresponding author

Correspondence to Doreen E. Szollosi .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutical and Administrative Sciences College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, USA

    Clinton B. Mathias

  2. Pharmaceutical Science and Research School of Pharmacy, Marshall University, Huntington, WV, USA

    Jeremy P. McAleer

  3. Department of Pharmaceutical Sciences School of Pharmacy and Physician Assistant Studies, University of Saint Joseph, Hartford, CT, USA

    Doreen E. Szollosi

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Szollosi, D.E., Hokeness, K., Manzoor, M.K. (2020). Mechanisms of Autoimmunity and Pharmacologic Treatments. In: Mathias, C., McAleer, J., Szollosi, D. (eds) Pharmacology of Immunotherapeutic Drugs. Springer, Cham. https://doi.org/10.1007/978-3-030-19922-7_7

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