AUTOIMMUNE DISEASE—a major health problem

Autoimmunity is a major cause of human disease. In the United States, at least 15 to 22 million people suffer from an autoimmune disease. About two thirds of them are women. In its modern context, the concept of autoimmunity as a cause of disease was introduced in 1956 by Rose and Witebsky when they discovered that the human disease chronic (Hashimoto’s) thyroiditis could be reproduced in experimental animals by immunization with thyroglobulin, a major protein constituent of the thyroid gland. We now know that upwards of 80 human diseases affecting every organ in the body are related to autoimmunity. The primary goal of our laboratory has been to understand the etiology and pathology of autoimmune disease by studying both human patients and experimental animals. From our own studies and those of others we have learned that autoimmune diseases are caused by the interaction of genetic traits and environmental factors. Currently we are investigating two models of autoimmune disease, thyroiditis and myocarditis.

Role of Cytokines in Thyroiditis

We are currently interested in the role of cytokines in the induction and development of autoimmune thyroiditis and are exploring the role of cytokine production in the initiation and progression of disease in genetically susceptible and non-susceptible strains of mice in an adjuvant-induced disease model. We have shown that the endogenous production of key cytokines, such as IFN-gamma and IL-12, may play a dramatic role in autoimmune pathogenesis. In a strain of mice genetically susceptible to autoimmune thyroiditis, we have found that dietary iodine markedly increases the severity of disease by enhancing to antigenic potency of thyroglobnpin.

Cardiac Myosin-Induced Autoimmune Myocarditis

Myocarditis and its sequela, dilated cardiomyopathy, are a major cause of heart failure in young adults. In humans, these diseases usually follow a viral infection.

Cardiac myosin is believed to be a major autoantigen in both human and murine virus-induced myocarditis. In our laboratory, we induce autoimmune myocarditis in genetically predisposed A/J and BALB/c mice by immunization with cardiac myosin. Following the cardiac myosin immunization, mice develop cardiac lesions which, in addition to other infiltrating cells, are composed of abundant eosinophils and scattered giant cells, producing a picture similar to fulminant human myocarditis.

At present, we are investigating the role of these cells as well as the role of antibodies and cytokines, IL-10, IL-4 and IFN-gamma in particular, in regulating the disease process.

AUTOIMMUNE DISEASE; Autoimmunity; Cytokines; Thyroiditis; Myocarditis; Coxsackievirus; Myosin; Thyroglobulin

1990 Doctor "Honoris Causa" in Medicine and Surgery from the University of Calgari, Italy

1992 Doctor "Honoris Causa" in Biological Science, University of Sassari, Italy

1992 Honorary life-time Member of the Ernest Witebsky Center Committee, State University of New York at Buffalo

1993 Abbot Award, The American Society for Microbiology ASM

1994 Distinguished Medical Alumnus Award, Medical Alumni Association, University at Buffalo School of Medicine

1997 Universidad Central de Venezuela Honorary Medal, Instituto de Inmunologia, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela

1994 Awarded Honorary Membership in the Oesterreichische Gesellschaft für Allergologie und Immunologie

1999 Elected Fellow, American Association for the Advancement of Sciences

1999 Elected Honorary Member, American Society for Microbiology

2003 ASM Professional Recognition Award

2004 AESKU Lifetime Achievement Award

2005 ASM Founders Metal

Afanasyeva M, Georgakopoulos D, Belardi DF, Bedja D, Fairweather D, Wang Y, Kaya Z, Gabrielson KL, Rodriguez ER, Caturegli P, Kass DA, ROSE NR. 2005. Impaired up-regulation of CD25 on CD4+ T cells in IFN-? knockout mice associated with progression of myocarditis to heart failure. Proc. Nat. Acad Sciences USA; Jan 4: 102, 1; 180-185.

Fairweather D, Frisancho-Kiss S, ROSE NR. 2005. Viruses as adjuvants for autoimmunity: evidence from Coxsackievirus-induced myocarditis.

Rev. Med. Virol. 15: 17-27.

Afanasyeva M, Georgakopoulos D, ROSE NR. 2004. Autoimmune myocarditis:

cellular mediators of cardiac dysfunction. Autoimmunity Reviews 3; 476-486.

Fairweather D, Frisancho-Kiss S, Yusung SA, Barrett MA, Davis SE, Gatewood SJL,

Njoku DB, ROSE NR. 2004. Interferon-? Protects against Chronic Viral Myocarditis by

Reducing Mast Cell Degranulation,fibrosis,and the Profibrotic Cytokines Transforming

Growth Factor-ß ,? Interleukin-1ß, and Interleukin-4 in the Heart; Am J Pathology; 165:6:

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