title: Molecular markers of systemic autoimmune disorders: the expression of MHC-located HSP70 genes is significantly associated with autoimmunity development.
abstract: OBJECTIVE
  To analyse the expression regulation of two inducible HSP70 genes - HSPA1A and HSPA1B - located within the major histocompatibility complex (MHC) in patients with various systemic autoimmune diseases and to prove the reliability of MHC-located HSP70 genes as molecular markers reflecting the autoimmune process.
  
  
  METHODS
  94 adult patients with idiopathic inflammatory myopathy (IIM, n=31), systemic lupus erythematosus (SLE, n=31) or systemic sclerosis (SSc, n=32) and 37 healthy individuals were analysed. The mRNA expression level was determined using quantitative real-time PCR method. The expression of intracellular HSP70 was established by flow cytometry, the extracellular HSP70 protein was measured in plasma samples using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  The expression of HSPA1A gene was significantly up-regulated in patients with autoimmune diseases (SLE: p<0.01; SSc: p<0.01; IIM: p<0.0001) compared to healthy controls. The expression of HSPA1B gene was increased only in patients with myositis (p<0.05). Furthermore, the HSPA1B gene expression is associated with the HLA-DRB1*03 risk allele in patients with IIM. In addition, we have found a relation between HSPA1A gene expression regulation and the presence of disease specific autoantibodies in patients with SLE and myositis. The level of intracellular HSP70 was not increased; however, the level of extracellular HSP70 protein was increased in patients suffering from SSc and IIM as compared to controls.
  
  
  CONCLUSIONS
  The results suggest an involvement of the MHC-linked HSP70 genes in the pathology of studied autoimmune disorders. Therefore, the HSPA1A and HSPA1B genes might serve as an interesting candidate molecule for development of distinct types of autoimmunities.
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic. remakova@revma.cz.
authors.forename: Martina
authors.initials: M
authors.lastname: Mišunová
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Tana
authors.initials: T
authors.lastname: Svitálková
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Pleštilová
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Olga
authors.initials: O
authors.lastname: Kryštufková
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Tegzová
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Radka
authors.initials: R
authors.lastname: Svobodová
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Hušáková
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Tomčík
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Bečvář
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Závada
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Herman
authors.initials: H
authors.lastname: Mann
authors.affiliation: Institute of Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Libor
authors.initials: L
authors.lastname: Kolesár
authors.affiliation: Institute of Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Antonij
authors.initials: A
authors.lastname: Slavčev
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Vencovský
authors.affiliation: Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Novota
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001323:Autoantibodies; D015551:Autoimmunity / Q000235:genetics*; D015415:Biomarkers; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000235:genetics* / Q000276:immunology; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; C490786:HSPA1A protein, human; C525621:HSPA1B protein, human