Viruses in Autoimmune Disease

Posted by Elaine Moore Jun 22, 2006

The Human T Cell Leukemia Virus Type I (HTLV-1) is a human retrovirus (virus that replicates through RNA), which causes viral illness or an asymptomatic (causing no symptoms) carrier state. However, in asymptomatic carriers, T-cell lymphoma may develop after 50 years of latency. Worldwide, 15 to 25 million people are infected with HTLV-1. HTLV-I is associated with the development of several different autoimmune disorders, including chronic arthropathy, pulmonary alveolitis, Sjogren's syndrome, uveitis, arthritis, connective tissue disease, and recently, autoimmune thyroid disease.

HTLV-1 is primarily known as the cause of adult T-cell leukemia (ATL) and a condition known as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is an inflammatory disease of the central nervous system. In recent studies, the proviral load or viral titer of HTLV-1 has been found to be significantly higher in HTLV-1 affected patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) than in HTLV-1 carriers without symptoms. In addition, viral DNA proteins p19 and gp21 and also the HTLV-1 antisense protein HBX have been in both thyroid tissue from people with autoimmune thyroid disease and in normal subjects. Based on this associations, researchers speculate that HTLV-1 may be a significant trigger for the development of these autoimmune thyroid disorders. The HTLV-1 virus is transmitted sexually, through breastfeeding, and through transufsions of contaminated blood products. HTLV-1 is a highly endemic disease in southern Japan, intertropical Africa, Latin America, and the Caribbean basin.

The first hints that HTLV-1 might be implicated in autoimmune thyroid disease occurred when reports of Hashimoto's thyroiditis occurring in patients with HTLV-1 infection and HAM/TSP surfaced. In addition, early reports showed the presence of Graves' disease in HTLV-1 carriers. Specifically in certain areas of Japan the incidence of HTLV-I was found to be 6.3 percent in patients with Hashimoto's thyroiditis although in the general population the incidence of HTLV-1 in this area is 2.2 percent. Studies of blood donors also showed a higher incidence of thyroid antibodies in donors who tested positive for HTLV-1. In most countries, including the United States, blood donors are tested for HTLV-1.

CD4+ T lymphocytes are the main target for both HTLV-1 and HIV, the retrovirus that causes AIDS. Japanese researchers have found that higher viral loads of HTLV-1 are associated with the development of autoimmune thyroid disease. To understand the mechanism for diseases development, they set out to find whether HTLV-1 was capable of infecting thyroid cells as well as lymphocytes. Studies showed that HTLV-1 produces Tax protein, which activates transcription of the viral genome, which facilitates viral reproduction. The HTLV-1 infected T cells produce various cytokines and cellular genes that contribute to autoimmune thyroid disease development. However, the ability of HTLV-1 to directly infect thyroid cells was not clearly demonstrated. Several studies have shown that more than 85 percent of patients with Graves' disease have detectable serum antibodies against human intracisternal type A retroviral particle. It's speculated that people with predisposing immune system genes who become infected with retroviruses such as HTLV-1 are susceptible to autoimmune thyroid disease.

In addition, HTLV-1 is suspected of causing a systemic immune-mediated inflammatory disease potently involving various tissues of the body, including those of the central nervous system. And while HTLV-1 has been found to be a significant trigger of autoimmune thyroid disease further studies on the effects of HTLV-1 infection of thyroid tissues are needed to determine the specific mechanism in autoimmune thyroid disease development.

Resources:

Nicot C, Dundt M, Human T-Cell Leukemia/Lymphoma Virus Type 1: Playing Hide and Seek, Nat Med 10: 197-201, 2004.

Takehiro Matsuda, Mariko Tomita, et al, Human T Cell Leukemia virus Type-I-Infected Patients with Hashimoto's Thyroiditis and Graves' Disease, Journal of Clinical Endocrinology and Metabolism Aug 2, 2005, 5704-5710.