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Molecular markers of systemic autoimmune disorders: the expression of MHC-located HSP70 genes is significantly associated with autoimmunity development
M. Mišunová1, T. Svitálková2, L. Pleštilová3, O. Kryštufková4, D. Tegzová5, R. Svobodová6, M. Hušáková7, M. Tomčík8, R. Bečvář9, J. Závada10, H. Mann11, L. Kolesár12, A. Slavčev13, J. Vencovský14, P. Novota15
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic. remakova@revma.cz
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
- Institute of Clinical and Experimental Medicine, Prague, Czech Republic.
- Institute of Clinical and Experimental Medicine, Prague, Czech Republic.
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
- Department of Rheumatology, First Faculty of Medicine, Charles University in Prague and Rheumatology Institute, Prague, Czech Republic.
CER9125
2017 Vol.35, N°1
PI 0033, PF 0042
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PMID: 28032847 [PubMed]
Received: 16/11/2015
Accepted : 04/04/2016
In Press: 28/12/2016
Published: 26/01/2017
Abstract
OBJECTIVES:
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.
