The role of Epstein-Barr virus infection in the development of autoimmune thyroid diseases.
BACKGROUND
Autoimmune thyroid diseases, including Graves' and Hashimoto's thyroiditis, are the most frequent autoimmune disorders. Viral infection, including Epstein-Barr virus (EBV), is one of the most frequently considered environmental factors involved in autoimmunity. Its role in the development of AITD has not been confirmed so far.


METHODS
Surgical specimens of Graves' and Hashimoto's diseases and nodular goitres were included in the study. The expression of EBV latent membrane protein 1 (LMP1) was analysed by immunohistochemistry, with the parallel detection of virus-encoded small nuclear non-polyadenylated RNAs (EBER) by in situ hybridisation.


RESULTS
In none of the Graves' disease specimens but in 34.5% of Hashimoto's thyroiditis cases the cytoplasmic expression of LMP1 was detected in follicular epithelial cells and in infiltrating lymphocytes. EBER nuclear expression was detected in 80.7% of Hashimoto's thyroiditis cases and 62.5% of Graves' disease cases, with positive correlation between LMP1 and EBER positivity in all Hashimoto's thyroiditis LMP1-positive cases.


CONCLUSIONS
We assume that high prevalence of EBV infection in cases of Hashimoto's and Graves' diseases imply a potential aetiological role of EBV in autoimmune thyroiditis. The initiation of autoimmune thyroiditis could start with EBV latency type III infection of follicular epithelium characterised by LMP1 expression involving the production of inflammatory mediators leading to recruitment of lymphocytes. The EBV positivity of the infiltrating lymphocytes could be only the presentation of a carrier state, but in cases with EBER+/ LMP1+ lymphocytes (transforming latent infection) it could represent a negative prognostic marker pointing to a higher risk of primary thyroid lymphoma development.
Andrea
A
Janegova
Department of Pathology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic; Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic. pavol.janega@fmed.uniba.sk.
Pavol
P
Janega
Boris
B
Rychly
Kristina
K
Kuracinova
Pavel
P
Babal
D020031:Epstein-Barr Virus Infections / Q000150:complications*; D015870:Gene Expression; D006111:Graves Disease / Q000209:etiology* / Q000821:virology; D050031:Hashimoto Disease / Q000209:etiology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000821:virology; D000072637:Thyroid Epithelial Cells / Q000821:virology; D014763:Viral Matrix Proteins / Q000235:genetics*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins