PRDM1 expression via human parvovirus B19 infection plays a role in the pathogenesis of Hashimoto thyroiditis

Hum Pathol. 2015 Dec;46(12):1913-21. doi: 10.1016/j.humpath.2015.08.009. Epub 2015 Sep 10.

Abstract

Ectopic lymphoid follicle infiltration is a key event in Hashimoto thyroiditis (HT). Positive regulatory domain zinc finger protein 1 (PRDM1), which is induced by antigen stimulation, can regulate all lymphocyte lineages. Several groups independently demonstrated that human parvovirus B19 (PVB19) is closely associated with HT. Hence, we determined whether PRDM1 is expressed in HT thyroid tissue and whether there is any correlation between PRDM1 expression and PVB19 in the pathogenesis of HT. We detected PRDM1 expression in HT (n = 86), normal thyroid tissue (n = 30), and nontoxic nodular goiter (n = 20) samples using immunohistochemistry. We also detected PVB19 protein in HT samples in a double-blind manner and analyzed the correlation between the 2 proteins using immunofluorescence confocal detection and coimmunoprecipitation. Furthermore, we detected changes of the expression levels of PRDM1 and PVB19 in transfected primary thyroid follicular epithelial cells using real-time quantitative polymerase chain reaction. We found that PRDM1 protein is significantly highly expressed in the injured follicular epithelial cells in HT (83/86 cases) than in normal thyroid cells (0/30 cases) or in nontoxic nodular goiter cells (0/20 cases) (P < .001). In HT, the PRDM1 expression pattern was the same as that of PVB19, whereas PRDM1 and PVB19 were coexistent in the involved epithelial cells. Statistical analysis showed a significant correlation between PRDM1 and PVB19 (P < .001). In addition, primary thyroid epithelial cells also showed PRDM1 up-regulation after PVB19 NS1 transfection. Our findings suggest a previously unrecognized role of PRDM1 and PVB19 in the pathogenesis of HT.

Keywords: Ectopic lymphoid tissue; Hashimoto's thyroiditis; Human parvovirus B19; Pathogenesis; Positive regulatory domain zinc finger protein 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Fluorescent Antibody Technique
  • Hashimoto Disease / immunology*
  • Hashimoto Disease / pathology
  • Hashimoto Disease / virology*
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Microscopy, Confocal
  • Middle Aged
  • Parvoviridae Infections / immunology*
  • Parvoviridae Infections / metabolism
  • Parvovirus B19, Human
  • Positive Regulatory Domain I-Binding Factor 1
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / biosynthesis*
  • Retrospective Studies
  • Tissue Array Analysis
  • Young Adult

Substances

  • Repressor Proteins
  • PRDM1 protein, human
  • Positive Regulatory Domain I-Binding Factor 1