Ricerca in clinica e in laboratorio

, Volume 17, Issue 4, pp 279–297 | Cite as

Pathogenetic aspects of organ-specific autoimmunity

  • Mario Ricci


In the last few years a great deal of information on the etiopathogenetic aspects of organ-specific autoimmune diseases (OSADS) has been obtained. It has been shown that genetic factors play an etiologic fundamental role. They are responsible for the dysregulation of the immune system and for the target organ susceptibility which favour the onset of the diseases. Putative environmental factors, such as viral infections, can act as initiating or precipitating events only in genetically predisposed individuals. Immunological mechanisms capable of triggering autoimmune responses have been demonstrated. Data obtained from experimental models and from humans suggest that the ongoing expansion of autoreactive T cells with specificity for autoantigens (AAgs) can be considered as the main immunological event capable of inducing and maintaining the target organ damage. These cells can activate different effector systems, i.e., autoantibody (AAb)-producing B cells, cells with cytotoxic activity, etc., by releasing different combinations of lymphokines. In overt diseases AAbs are directly involved in the pathogenesis of lesions due to autoimmune responses against functional molecules and cellular receptors. The pathogenesis of the common inflammatory destructive lesions of the target organs is more complex and not yet clarified. A large proportion of T cells present in the inflammatory infiltrates are apparently not directed to the AAgs. Most cells display cytolytic activity and may contribute to tissue damage by releasing lymphokines which activate other cells and cascade the process. Vicious cycles, i.e., upregulation of class II and I molecules, alterations of the cytokine network, etc., are supposed to be involved in the maintenance of target organ lesions.


Autoantibodies Autoantigens Autoimmune diseases Autoimmunity B cells Genetics Idiotypes Inflammation T cells Thyroiditis 


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  1. 1.
    Alper C. A., Awdeh Z. L., Raum D. D., Yunis E. J.: Extended major histocompatibility complex haplotypes in man: role of alleles analogous to murine t mutants — Clin. Immunol. Immunopathol.24, 276, 1982.PubMedCrossRefGoogle Scholar
  2. 2.
    Batchelor J. R.: Genetic role in autoimmunity. In:Schindler R. (Ed.): Cyclosporin in autoimmune diseases. 1st Int. Symp., Basel, March 18–20, 1985; p. 16.Google Scholar
  3. 3.
    Böhme J., Carlsson B., Wallin J., Möller E., Persson B., Peterson P. A., Rask L.: Only one DQ-β restriction fragment pattern of each DR specificity is associated with insulin-dependent diabetes — J. Immunol.137, 941, 1986.PubMedGoogle Scholar
  4. 4.
    Boitard C., Bach J. F.: Cell-mediated versus humoral immunity in autoimmune diseases and their pharmacologic control, with particular reference to type I diabetes mellitus. In:Cruse J. M., Lewis R. E. Jr. (Eds): Immunoregulation and autoimmunity. Karger, Basel, 1986; vol. 3, p. 183.Google Scholar
  5. 5.
    Bottazzo G. F., Pujol-Borrel R., Hanafusa T.: Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity — Lancetii, 1115, 1983.CrossRefGoogle Scholar
  6. 6.
    Bottazzo G. F., Todd I., Mirakian R., Belfiore A., Pujol-Borrel R.: Organ-specific autoimmunity: a 1986 overview — Immunol. Rev.94, 137, 1986.PubMedCrossRefGoogle Scholar
  7. 7.
    Canonica G. W., Bagnasco M., Moretta L., Cocco R., Ferrini O., Giordana G.: Human T lymphocyte subpopulations in Hashimoto’s disease — J. clin. Endocrinol.52, 553, 1981.Google Scholar
  8. 8.
    Cohen I. R.: Regulation of autoimmune disease. Physiological and therapeutic — Immunol. Rev.94, 5, 1986.PubMedCrossRefGoogle Scholar
  9. 9.
    Del Prete G. F., Maggi E., Mariotti S., Tiri A., Vercelli D., Parronchi P., Macchia D., Pinchera A., Ricci M., Romagnani S.: Cytolytic T lymphocytes with natural killer activity in thyroid infiltrate of patients with Hashimoto’s thyroiditis — J. clin. Endocrinol.62, 52, 1986.Google Scholar
  10. 10.
    Del Prete G. F., Mariotti S., Tiri A., Ricci M., Pinchera A., Romagnani S.: Characterization of thyroid-infiltrating lymphocytes in Hashimoto’s thyroiditis. Detection of B and T cells specific for thyroid antigens — Acta endocrinol. (Kbh.)281, 111, 1987.Google Scholar
  11. 11.
    Del Prete G. F., Tiri A., Mariotti S., Pinchera A., Ricci M., Romagnani S.: Enhanced production of gamma interferon by thyroid-derived T cell clones from patients with Hashimoto’s thyroiditis — Clin. exp. Immunol. 1987. (In press).Google Scholar
  12. 12.
    Del Prete G. F., Tiri A., Mariotti S., Romagnani S., Ricci M.: Functional analysis of thyroid-infiltrating T lymphocytes in Hashimoto’s thyroiditis. In:Pinchera A. (Ed.): Thyroid autoimmunity. Plenum Press, New York, 1987. (In press).Google Scholar
  13. 13.
    Del Prete G. F., Vercelli D., Tiri A., Maggi E., Mariotti S., Pinchera A., Ricci M., Romagnani S.:In vivo activated cytotoxic T cells in the thyroid infiltrate of patients with Hashimoto’s thyroiditis — Clin. exp. Immunol.65, 140, 1986.PubMedGoogle Scholar
  14. 14.
    Doniach D., Bottazzo G. F.: Autoimmune endocrine disorders — Hosp. Update, October 1983, p. 1145.Google Scholar
  15. 15.
    Dwyer D. S., Bradley R. J., Urquhart C. K., Kearney J. F.: Naturally occurring anti-idiotypic antibodies in myasthenia gravis patients — Nature (Lond.)301, 611, 1983.CrossRefGoogle Scholar
  16. 16.
    Dwyer D. S., Vakil M., Kearney J. F.: Idiotypic network connectivity and a possible cause of myasthenia gravis — J. exp. Med.164, 1310, 1986.PubMedCrossRefGoogle Scholar
  17. 17.
    Ebner S. A., Stein M. E., Minami M., Dorf M. E., Stadecker M. J.: Murine thyroid follicular epithelial cells can be induced to express class II (Ia) gene products but fail to present antigenin vitro — Cell. Immunol.104, 154, 1987.PubMedCrossRefGoogle Scholar
  18. 18.
    Eisenbarth G. S.: Type I diabetes mellitus. A chronic autoimmune disease — New Engl. J. Med.314, 1360, 1986.PubMedGoogle Scholar
  19. 19.
    Eisenbarth G. S.: Genes, generator of diversity, glycoconjugates, and acetylcholine receptor insufficiency in type I diabetes — Diabetes36, 355, 1987.PubMedGoogle Scholar
  20. 20.
    Garlepp M. J., Dawkins R. L., Christansen F. T.: HLA antigens and acetylcholine receptor antibodies in penicillamine-induced myasthenia gravis — Brit. med. J.286, 338, 1983.CrossRefGoogle Scholar
  21. 21.
    Greenstein J. I., McFarland H. F., Richter J. R.: Characterization of antigen-specific T cells in multiple sclerosis twins with elevated proliferative responses to measles virus — J. Immunol.137, 546, 1986.PubMedGoogle Scholar
  22. 22.
    Hanafusa T., Pujol-Borrel R., Chiovato L., Russel R. C. G., Doniach D., Bottazzo G. F.: Aberrant expression of HLA-DR antigen on thyrocytes in Graves’ disease: relevance for autoimmunity — Lancetii, 1111, 1983.CrossRefGoogle Scholar
  23. 23.
    Iwatani Y., Gerstein H., Iitaka M., Row V. V., Volpè R.: Thyrocyte DR expression induced by autologous Graves’ lymphocytes and supernatants from mitogen-stimulated lymphocytes. In: Proc. 9th Int. Thyroid Congr., São Paulo, September 1–6, 1985. Plenum Press, New York. (In press).Google Scholar
  24. 24.
    Kantor F. S.: Autoimmunity-regulation disorders. In: The American Academy of Allergy and Immunology. 43rd Annual Meeting, February 1987. Postgraduate Course Syllabus, Washington, 1987; p. 73.Google Scholar
  25. 25.
    Karlsson F. A., Totterman T. H., Jansson R.: Subacute thyroiditis: activated HLA-DR and interferon-γ expressing T cytotoxic/suppressor cells in thyroid tissue and peripheral blood — Clin. Endocrinol.25, 487, 1986.CrossRefGoogle Scholar
  26. 26.
    Lefvert A. K.: Auto-anti-idiotypic immunity and acetylcholine receptors. In:Cruse J. M., Lewis R. E. Jr. (Eds): Immunoregulation and autoimmunity. Karger, Basel, 1986; vol. 3, p. 285.Google Scholar
  27. 27.
    Londei M., Bottazzo G. F., Feldmann M.: Human T-cell clones from autoimmune thyroid glands; specific recognition of autologous thyroid cells — Science228, 85, 1985.PubMedCrossRefGoogle Scholar
  28. 28.
    Mackenzie W. A., Davies T. F.: An intrathyroidal T-cell clone specifically cytotoxic for human thyroid cells — Immunology61, 101, 1987.PubMedGoogle Scholar
  29. 29.
    Margolik J. B., Su-Ming H., Volkman D. J., Burman K. D., Fauci A. S.: Immunohistochemical characterization of intrathyroid lymphocytes in Graves’ disease. Interstitial and intraepithelial populations — Amer. J. Med.76, 815, 1984.CrossRefGoogle Scholar
  30. 30.
    Mariotti S., Chiovato L., Vitti P., Anelli S., Bechi R., Lopez G., Lombardi A., Tiri A., Pinchera A.: The thyroid microsomial/microvillar autoantigen — Folia allergol. immunol. clin.1, 1, 1987.Google Scholar
  31. 31.
    Mariotti S., Del Prete G. F., Maggi E., Pisani S., Russova A., Almerigogna F., Pinchera A., Romagnani S., Ricci M.: Surface markers and function of circulating thyroid autoantibody-producing cells — J. clin. Endocrinol.58, 18, 1983.CrossRefGoogle Scholar
  32. 32.
    Masala C., Smurra G., Di Prima M. A., Amendolea M. A., Celestino D., Salsano F.: Gastric parietal cell antibodies: demonstration by immunofluorescence of their reactivity with the surface of the gastric parietal cells — Clin. exp. Immunol.41, 271, 1980.PubMedGoogle Scholar
  33. 33.
    Masuda A., Tsushima T., Shizume K., Shibata K., Kinoshita A., Omori M., Sato Y., Demura H., Ohashi H., Odagiri R., Hirata Y.: Insulin autoimmune syndrome with insulin-resistant diabetes at the incipient stage prior to hypoglycemic attacks — J. endocrinol. Invest.9, 507, 1986.PubMedGoogle Scholar
  34. 34.
    Nakamura M., Davies T. F., Ginsberg-Fellner F., Notkins A. L., Casali P.: Anti-self human B cell repertoire in normal and autoimmune conditions — Fed. Proc.46, 1382, 1987.Google Scholar
  35. 35.
    Noma T., Yata J.: Establishment of a human T cell hybridoma cell line producing suppressor factor specific for anti-thyroglobulin antibody production — J. Immunol.9, 2929, 1987.Google Scholar
  36. 36.
    Preud’Homme G. J., Fuks A., Colle E., Guttman R. D.: Isolation of T-lymphocyte lines with specificity for islet cell antigens from spontaneously diabetic (insulin-dependent) rats — Diabetes33, 801, 1984.CrossRefGoogle Scholar
  37. 37.
    Rabinowe S. L., Larsen P. R., Antman E. M., George K. L., Friedman P. L., Jackson R. A., Eisenbarth G. S.: Amiodarone therapy and autoimmune thyroid disease. Increase in a new monoclonal antibody-defined T cell subset — Amer. J. Med.81, 53, 1986.PubMedCrossRefGoogle Scholar
  38. 38.
    Rayner D. C., Delves P. J., Warren D., Roitt I. M., Champion B. R.: T-cell hybridomas specific for self and foreign thyroglobulins — Immunology60, 231, 1987.PubMedGoogle Scholar
  39. 39.
    Ricci M., Passaleva A., Romagnani S.: Recenti acquisizioni sulla tolleranza immunologica e sulle modalità di autoimmunizzazione — Rec. Progr. Med.61, 584, 1976.Google Scholar
  40. 40.
    Ricci M., Romagnani S., Passaleva A., Biliotti G.:In vivo andin vitro immunological responses to heterologous and homologous thyroglobulin in guinea pigs immunized with heterologous thyroid extracts in Freund’s complete adjuvants — Int. Arch. Allergy41, 138, 1971.PubMedGoogle Scholar
  41. 41.
    Roitt I. M.: Prevailing theories in autoimmune disorders. In:Schindler R. (Ed.): Cyclosporin in autoimmune diseases. 1st Int. Symp., Basel., March 18–20, 1985; p. 5.Google Scholar
  42. 42.
    Romagnani S., Ricci M., Passaleva A., Biliotti G.: Cell-mediated immune responses to heterologous and homologous thyroglobulin in guinea pigs immunized with heterologous thyroid extracts — Immunology19, 599, 1970.PubMedGoogle Scholar
  43. 43.
    Rose N. R.: The thyroid gland as source and target of autoimmunity — Lab. Invest.52, 117, 1985.PubMedGoogle Scholar
  44. 44.
    Rose N. R., Kong Y. M., Okayasu I., Giraldo A. A., Beisel K., Sundick R. S.: T-cell regulation in autoimmune thyroiditis — Immunol. Rev.55, 299, 1981.PubMedCrossRefGoogle Scholar
  45. 45.
    Ruff J., Carayon P., Lissitzsky S.: Various expressions of a unique anti-human thyroglobulin antibody repertoire in normal state and autoimmune disease — Europ. J. Immunol.15, 268, 1985.CrossRefGoogle Scholar
  46. 46.
    Sakaguchi S., Fukuma K., Kuribayashi K., Masuda T.: Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as possible cause of autoimmune disease — J. exp. Med.161, 72, 1985.PubMedCrossRefGoogle Scholar
  47. 47.
    Schoenfeld Y., Schwartz R. S.: Immunologic and genetic factors in autoimmune diseases — New Engl. J. Med.311, 1019, 1984.Google Scholar
  48. 48.
    Schwartz R. S.: Autoantibodies and normal antibodies. In:Cinader B., Miller R. G. (Eds): Progress in immunology. Proc. 6th Int. Congr. of Immunology, Toronto, 1986. Academic Press, London, 1986; p. 478.Google Scholar
  49. 49.
    Serafini U., Masala C., Costanzi-Langer M., Pala A. M.: Autoimmune diathesis and thyroid diseases. In: Proc. I Europ. Congr. of Pathology, Varsavia, June 1–3, 1966; p. 111 — Folia allergol. (Roma)13, 328, 1966.Google Scholar
  50. 50.
    Serafini U., Masala C., Ricci M.: Aspetti clinici dell’autoimmunità organo-specifica. In: 78° Congr. Soc. ital. Med. int., Firenze, October 19–22, 1977. Pozzi L. ed., Roma, 1977.Google Scholar
  51. 51.
    Sriram S., Ranges G. E.: Immunotherapy of autoimmune disease with T cell subset-specific antibodies. In:Cruse J. M., Lewis R. E. Jr. (Eds): Autoimmunoregulation and autoimmune disease. Karger, Basel, 1987; vol. 4, p. 275.Google Scholar
  52. 52.
    Tami J. A., Urso O. E., Krolick K.: T cell hybridomas reactive with the acetylcholine receptor and its subunits — J. Immunol.138, 732, 1985.Google Scholar
  53. 53.
    Uchigata Y., Spitalnick S. L., Tachiwaki O., Salatak F., Notkins A. L.: Pancreatic islet cell surface glycoproteins containing Galβ1-4G1cNAc-R identified by a cytotoxic monoclonal autoantibody — J. exp. Med.165, 124, 1987.PubMedCrossRefGoogle Scholar
  54. 54.
    van Eden W., Holoshitz J., Cohen I.: Antigen mimicry between mycobacteria and cartilage proteoglycans. In:Cruse J. M., Lewis R. E. Jr. (Eds): Autoimmunoregulation and autoimmune disease. Karger, Basel, 1987; vol. 4, p. 144.Google Scholar
  55. 55.
    Wick G., Hala K., Wolf H., Ziemiecki A., Sundick R. S., Stöffler-Meilicke M., de Baets M.: The role of genetically-determined primary alterations of the target organ in the development of spontaneous autoimmune thyroiditis in obese strain (OS) chickens — Immunol. Rev.94, 113, 1986.PubMedCrossRefGoogle Scholar
  56. 56.
    Zanetti M.: Idiotype network and its relevance to autoimmune diseases. Functional considerations. In:Cruse J. M., Lewis R. E. Jr. (Eds): Immunoregulation and autoimmunity. Karger, Basel, 1986; vol. 3, p. 253.Google Scholar

Copyright information

© Casa Editrice «Il Ponte» 1987

Authors and Affiliations

  • Mario Ricci
    • 1
  1. 1.Cattedra di Allergologia e Immunologia Clinica Clinica Medica IIIUniversità degli Studi di Firenze Policlinico di CareggiFirenzeItalia

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