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.
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.
Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy.
Antonella
A
Marino Gammazza
Manfredi
M
Rizzo
Roberto
R
Citarrella
Francesca
F
Rappa
Claudia
C
Campanella
Fabio
F
Bucchieri
Angelo
A
Patti
Dragana
D
Nikolic
Daniela
D
Cabibi
Giandomenico
G
Amico
Pier Giulio
PG
Conaldi
Pier Luigi
PL
San Biagio
Giuseppe
G
Montalto
Felicia
F
Farina
Giovanni
G
Zummo
Everly
E
Conway de Macario
Alberto J L
AJ
Macario
Francesco
F
Cappello
D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood; D002462:Cell Membrane / Q000378:metabolism*; D018834:Chaperonin 60 / Q000097:blood* / Q000737:chemistry*; D019295:Computational Biology; D003429:Cross Reactions / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006042:Goiter / Q000097:blood / Q000276:immunology / Q000473:pathology; D050031:Hashimoto Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism; D007453:Iodide Peroxidase / Q000737:chemistry* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000097:blood* / Q000737:chemistry*; D008969:Molecular Sequence Data; D024862:Oxyphil Cells / Q000378:metabolism* / Q000473:pathology; D040681:Structural Homology, Protein; D013954:Thyroglobulin / Q000737:chemistry* / Q000276:immunology; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D001323:Autoantibodies; D018834:Chaperonin 60; C060293:HSPD1 protein, human; D016023:Integrins; D024101:Mitochondrial Proteins; C006606:anti-thyroglobulin; D013954:Thyroglobulin; D007453:Iodide Peroxidase