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Cell Stress and Chaperones

, Volume 19, Issue 3, pp 343–353 | Cite as

Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis

  • Antonella Marino Gammazza
  • Manfredi Rizzo
  • Roberto Citarrella
  • Francesca Rappa
  • Claudia Campanella
  • Fabio Bucchieri
  • Angelo Patti
  • Dragana Nikolic
  • Daniela Cabibi
  • Giandomenico Amico
  • Pier Giulio Conaldi
  • Pier Luigi San Biagio
  • Giuseppe Montalto
  • Felicia Farina
  • Giovanni Zummo
  • Everly Conway de Macario
  • Alberto J. L. Macario
  • Francesco CappelloEmail author
Original Paper

Abstract

The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto’s thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on fine needle aspiration cytology. By bioinformatics, we found regions in the Hsp60 molecule with remarkable structural similarity with the thyroglobulin (TG) and thyroid peroxidase (TPO) molecules, which supports the notion that autoantibodies against TG and TPO are likely to recognize Hsp60 on the plasma membrane of oncocytes. This was also supported by data obtained by ELISA, showing that anti-TG and anti-TPO antibodies cross-react with human recombinant Hsp60. Antibody-antigen (Hsp60) reaction on the cell surface could very well mediate thyroid cell damage and destruction, perpetuating inflammation. Experiments with recombinant Hsp60 did not show stimulation of cytokine production by peripheral blood mononuclear cells from HT patients. All together, these results led us to hypothesize that Hsp60 may be an active player in HT pathogenesis via an antibody-mediated immune mechanism.

Keywords

Hsp60 Hashimoto's thyroiditis (HT) Thyroglobulin (TG) Thyroid peroxidase (TPO) Autoantibodies Oncocytes Hurthle cells Thyrocytes Chaperonin Autoimmunity 

Notes

Acknowledgements

This work was partly supported by IEMEST (FC, AJLM) and was carried out under the umbrella of the agreement between IEMEST and IMET signed March 26, 2012.

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Copyright information

© Cell Stress Society International 2013

Authors and Affiliations

  • Antonella Marino Gammazza
    • 1
    • 2
  • Manfredi Rizzo
    • 2
    • 3
  • Roberto Citarrella
    • 3
  • Francesca Rappa
    • 1
    • 2
  • Claudia Campanella
    • 1
    • 2
  • Fabio Bucchieri
    • 1
    • 2
  • Angelo Patti
    • 2
    • 3
  • Dragana Nikolic
    • 1
    • 3
  • Daniela Cabibi
    • 4
  • Giandomenico Amico
    • 5
  • Pier Giulio Conaldi
    • 5
  • Pier Luigi San Biagio
    • 6
  • Giuseppe Montalto
    • 3
  • Felicia Farina
    • 1
  • Giovanni Zummo
    • 1
  • Everly Conway de Macario
    • 7
  • Alberto J. L. Macario
    • 2
    • 7
  • Francesco Cappello
    • 1
    • 2
    • 6
    Email author
  1. 1.Department of Experimental Biomedicine and Clinical NeurosciencesUniversity of PalermoPalermoItaly
  2. 2.Euro-Mediterranean Institute of Science and TechnologyPalermoItaly
  3. 3.Department of Internal Medicine and Medical SpecialtiesUniversity of PalermoPalermoItaly
  4. 4.Department of Human PathologyUniversity of PalermoPalermoItaly
  5. 5.Istituto Mediterraneo per i Trapianti e Terapie (ISMETT) ad Alta Specializzazione and RIMED FoundationPalermoItaly
  6. 6.Institute of Biophysics (IBF)National Research Council of Italy (CNR)PalermoItaly
  7. 7.Department of Microbiology and Immunology, School of MedicineUniversity of Maryland at Baltimore, and IMET, Columbus CenterBaltimoreUSA

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