Hashimoto’s thyroiditis (HT) is the most common of all thyroid diseases, with continuously increasing prevalence, and is characterized by abundant lymphocyte infiltrate and thyroid impairment, caused by various cell- and antibody-mediated immune processes 1. In addition to genetic background, several viruses, including herpesviruses, have been suggested to play a role as possible environmental triggers of disease, but conclusive data are still lacking 2-3. The tentative correlation of Human Herpesvirus 6 (HHV-6) with other autoimmune pathologies and its anecdotal presence in HT specimens 4, prompted us to study a possible association between HHV-6 and HT. Our analysis of fine needle thyroid aspirates and blood from HT patients and controls, showed that HHV-6 prevalence and load are highly increased in HT patients (prevalence 82% vs 10%, p=0.001). Furthermore, HT-derived thyroid samples harbor active virus, whereas HHV-6 is strictly latent in the few virus-positive controls. Also, thyrocytes rather than infiltrating lymphocytes contain and support active virus replication. The tropism of HHV-6 for thyroid cells was confirmed by in vitro infection experiments, showing that thyrocytes are permissive to HHV-6 replication, which induces de novo expression of HLA class II antigens on their surface, allowing them to behave as professional APCs. Interestingly, immune cells from HT patients kill HHV-6-infected thyrocytes more efficiently than cells derived from controls. Also, HT patients, but not controls, have specific CD4+ and CD8+ T-cell responses to HHV-6 U94 protein, and specific antibodies directed against HHV-6 U94 antigen.. Although it is difficult to prove etiologic links between viral infections and diseases, especially in the case of a ubiquitous agent such as HHV-6, our findings argue for a potential role for HHV-6 in the development or triggering of HT, and suggest that the presence of a specific immune background is as important as virus infection itself in determining the evolution of the disease.
HHV-6 e tiroidite autoimmune: indizi di possibili meccanismi immunovirologici
CASELLI, Elisabetta
2012
Abstract
Hashimoto’s thyroiditis (HT) is the most common of all thyroid diseases, with continuously increasing prevalence, and is characterized by abundant lymphocyte infiltrate and thyroid impairment, caused by various cell- and antibody-mediated immune processes 1. In addition to genetic background, several viruses, including herpesviruses, have been suggested to play a role as possible environmental triggers of disease, but conclusive data are still lacking 2-3. The tentative correlation of Human Herpesvirus 6 (HHV-6) with other autoimmune pathologies and its anecdotal presence in HT specimens 4, prompted us to study a possible association between HHV-6 and HT. Our analysis of fine needle thyroid aspirates and blood from HT patients and controls, showed that HHV-6 prevalence and load are highly increased in HT patients (prevalence 82% vs 10%, p=0.001). Furthermore, HT-derived thyroid samples harbor active virus, whereas HHV-6 is strictly latent in the few virus-positive controls. Also, thyrocytes rather than infiltrating lymphocytes contain and support active virus replication. The tropism of HHV-6 for thyroid cells was confirmed by in vitro infection experiments, showing that thyrocytes are permissive to HHV-6 replication, which induces de novo expression of HLA class II antigens on their surface, allowing them to behave as professional APCs. Interestingly, immune cells from HT patients kill HHV-6-infected thyrocytes more efficiently than cells derived from controls. Also, HT patients, but not controls, have specific CD4+ and CD8+ T-cell responses to HHV-6 U94 protein, and specific antibodies directed against HHV-6 U94 antigen.. Although it is difficult to prove etiologic links between viral infections and diseases, especially in the case of a ubiquitous agent such as HHV-6, our findings argue for a potential role for HHV-6 in the development or triggering of HT, and suggest that the presence of a specific immune background is as important as virus infection itself in determining the evolution of the disease.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
