Heat-shock protein 90: a novel autoantigen in human carotid atherosclerosis.
The known role of heat-shock proteins (HSPs) in the pathogenesis of atherosclerosis prompted us to investigate whether HSP90 is a target autoantigen of immune responses in patients with carotid atherosclerosis.


RESULTS
The presence of HSP90 on 26 cryostat and 6 paraffin embedded sections of carotid atherosclerotic plaques was determined by immunohistochemistry and immunofluorescence. Plaque-infiltrating T lymphocytes from 9 patients and circulating PBMC from 26 patients and 21 healthy subjects were tested by cell proliferation assay and by flow cytometry and ELISA for cytokine production in response to HSP90. ELISA was used to detect soluble HSP90 and anti-HSP90 antibodies in serum samples. Strong HSP90 immunoreactivity was detected in the muscle and endothelial cell layer and in the inflammatory infiltrate of carotid plaques. Plaque-derived and circulating T lymphocytes from patients proliferated in response to HSP90 whereas cells from healthy subjects did not. HSP90-specific T lymphocytes expressed IFN-gamma and IL-4 suggesting concomitant Th1 and Th2 activation. ELISA detected soluble HSP90 in 42% and anti-HSP90 antibodies in 46% of patients' sera.


CONCLUSIONS
These new findings, showing that HSP90 is overexpressed in plaque and serum from patients with atherosclerosis and induces an immune response in these patients, implicate HSP90 as a possible target autoantigen in the pathogenesis of carotid atherosclerosis.
Businaro
Rita
R
Department of Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy. rita.businaro@uniroma1.it
Profumo
Elisabetta
E
Tagliani
Angela
A
Buttari
Brigitta
B
Leone
Stefano
S
D'Amati
Giulia
G
Ippoliti
Flora
F
Leopizzi
Martina
M
D'Arcangelo
Daniela
D
Capoano
Raffaele
R
Fumagalli
Lorenzo
L
Salvati
Bruno
B
Riganò
Rachele
R
D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000097:blood / Q000276:immunology*; D002340:Carotid Artery Diseases / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018841:HSP90 Heat-Shock Proteins / Q000097:blood / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D018841:HSP90 Heat-Shock Proteins; C508598:IL4 protein, human; D015847:Interleukin-4; D007371:Interferon-gamma