Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis

Hashimoto's thyroiditis (ht) is the most common of all thyroid diseases and is characterized by abundant lymphocyte infiltrate and thyroid impairment,caused by various cell- and antibody-mediated immune processes. viral infections have been suggested as possible environmental triggers,but conclusive data are not available. we analyzed the presence and transcriptional state of human herpesvirus 6 (hhv-6) in thyroid fine needle aspirates (fna) and peripheral blood mononuclear cells (pbmcs) from 34 ht patients and 28 controls,showing that hhv-6 dna prevalence (82% vs. 10%,p≤0.001) and viral load were significantly increased in fna from ht patients,and thyrocytes from ht fna displayed a 100-fold higher hhv-6 dna load compared to infiltrating lymphocytes. in addition,while hhv-6 was strictly latent in positive samples from controls,a low grade acute infection was detected in ht samples. hhv-6 variant characterization was carried out in 10 ht fna samples,determining that all specimens harbored hhv-6 variant a. the tropism of hhv-6 for thyroid cells was verified by infection of nthy-ori3-1,a thyroid follicular epithelial cell line,showing that thyrocytes are permissive to hhv-6 replication,which induces de novo expression of hla class ii antigens. furthermore,hhv-6-infected nthy-ori3-1 cells become targets for nk-mediated killing,nk cells from ht patients show a significantly more efficient killing of hhv-6 infected thyroid cells than healthy controls,and ht patients have increased t-cell responses to hhv-6 u94 protein,associated to viral latency. these observations suggest a potential role for hhv-6 (possibly variant a) in the development or triggering of ht. © 2012 caselli et al.