PDIA3, HSPA5 and vimentin, proteins identified by 2-DE in the valvular tissue, are the target antigens of peripheral and heart infiltrating T cells from chronic rheumatic heart disease patients.
Rheumatic fever (RF) is a post-infectious autoimmune disease due to sequel of group A streptococcus (GAS) pharyngitis. Rheumatic heart disease (RHD), the major manifestation of RF, is characterized by inflammation of heart valves and myocardium. Molecular mimicry between GAS antigens and host proteins has been shown at B and T cell level. However the identification of the autoantigens recognized by B and T cells within the inflammatory microenvironment of heart tissue in patients with RHD is still incompletely elucidated. In the present study, we used two-dimensional gel electrophoresis (2-DE) and mass spectrometry to identify valvular tissue proteins target of T cells from chronic RHD patients. We could identify three proteins recognized by heart infiltrating and peripheral T cells as protein disulfide isomerase ER-60 precursor (PDIA3), 78kD glucose-regulated protein precursor (HSPA5) and vimentin, with coverage of 45%, 43 and 34%, respectively. These proteins were recognized in a proliferation assay by peripheral and heart infiltrating T cells from RHD patients suggesting that they may be involved in the autoimmune reactions that leads to valve damage. We also observed that several other proteins isolated by 2-DE but not identified by mass spectrometry were also recognized by T cells. The identified cardiac proteins are likely relevant antigens involved in T cell-mediated autoimmune responses in RF/RHD that may contribute to the development of RHD.
Heart Institute (InCor), University of São Paulo, São Paulo, Brazil.
Kellen C
KC
Faé
Danielle
D
Diefenbach da Silva
Angelina M B
AM
Bilate
Ana C
AC
Tanaka
Pablo M A
PM
Pomerantzeff
Maria Helena
MH
Kiss
Clovis A A
CA
Silva
Edecio
E
Cunha-Neto
Jorge
J
Kalil
Luiza
L
Guilherme
D015153:Blotting, Western; D002908:Chronic Disease; D015180:Electrophoresis, Gel, Two-Dimensional; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D013058:Mass Spectrometry; D008943:Mitral Valve / Q000737:chemistry / Q000276:immunology*; D018832:Molecular Chaperones / Q000097:blood / Q000235:genetics / Q000276:immunology*; D019704:Protein Disulfide-Isomerases / Q000097:blood / Q000235:genetics / Q000276:immunology*; D040901:Proteomics; D012214:Rheumatic Heart Disease / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014746:Vimentin / Q000097:blood / Q000235:genetics / Q000276:immunology*
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D014746:Vimentin; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human