Article

Antibodies against the human heat shock protein hsp70 in patients with severe coronary artery disease.

3rd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Immunological investigations (impact factor: 1.16). 31(3-4):219-31.
Source: PubMed

ABSTRACT Heat shock proteins (hsps) play complex role in the function of the immune system, they can activate both humoral and cellular immune response, as well the complement system. Although autoimmunity to hsp70 was implicated in certain autoimmune diseases and other conditions, the exact role of anti-hsp70 antibodies is not known. It was demonstrated by our previous work and other's findings that antibodies against the 60 kDa hsps are strongly associated with coronary atherosclerosis and carotis disease. It is also known that there is increased hsp70 expression at different sites of atherosclerosis. Therefore our aim was to study whether level of anti-hsp70 antibodies correlate with the presence of severe coronary artery disease (CAD). We measured and compared anti-hsp70 IgG antibody levels in CAD patients (n = 99) and healthy subjects (n = 99) with ELISA. The frequency of these antibodies was high in both groups and there was no significant difference in the median level of anti-hsp70 antibodies between patients with severe CAD and controls (653 (400-1141) vs. 630 (326-1152) AU/mL, P = 0.337). Adjustment for age, sex, BMI and lipid parameters did not change this result. Furthermore we did not find a correlation between anti-hsp70 antibody levels and certain risk factors of CAD (age, lipid parameters, body mass index, C-reactive protein, gender, smoking, diabetes and anti-hsp60 antibodies). By contrast, in accordance with our previous findings, anti-hsp60 and anti-hsp65 antibody levels were significantly higher in CAD patients, compared to this control group (p < 0.0001 for both variables). We did not find any correlation between the levels of anti-hsp70 and anti-hsp60 or anti-hsp65 antibodies either in the patients or the controls. The exact role of hsp70 in atherosclerosis is controversial, but we suggest that humoral immunity against human hsp70 does not contribute to coronary atherosclerosis in contrast to antibodies against 60kDa hsps.

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    Article: Mutant HSP70 Reverses Autoimmune Depigmentation in Vitiligo.
    Jeffrey A Mosenson, Andrew Zloza, John D Nieland, Elizabeth Garrett-Mayer, Jonathan M Eby, Erica J Huelsmann, Previn Kumar, Cecele J Denman, Andrew T Lacek, Frederick J Kohlhapp, Ahmad Alamiri, Tasha Hughes, Steven D Bines, Howard L Kaufman, Andreas Overbeck, Shikhar Mehrotra, Claudia Hernandez, Michael I Nishimura, Jose A Guevara-Patino, I Caroline Le Poole
    [show abstract] [hide abstract]
    ABSTRACT: Vitiligo is an autoimmune disease characterized by destruction of melanocytes, leaving 0.5% of the population with progressive depigmentation. Current treatments offer limited efficacy. We report that modified inducible heat shock protein 70 (HSP70i) prevents T cell-mediated depigmentation. HSP70i is the molecular link between stress and the resultant immune response. We previously showed that HSP70i induces an inflammatory dendritic cell (DC) phenotype and is necessary for depigmentation in vitiligo mouse models. Here, we observed a similar DC inflammatory phenotype in vitiligo patients. In a mouse model of depigmentation, DNA vaccination with a melanocyte antigen and the carboxyl terminus of HSP70i was sufficient to drive autoimmunity. Mutational analysis of the HSP70i substrate-binding domain established the peptide QPGVLIQVYEG as invaluable for DC activation, and mutant HSP70i could not induce depigmentation. Moreover, mutant HSP70i bound human DCs and reduced their activation, as well as induced a shift from inflammatory to tolerogenic DCs in mice. HSP70i-encoding DNA applied months before spontaneous depigmentation prevented vitiligo in mice expressing a transgenic, melanocyte-reactive T cell receptor. Furthermore, use of HSP70i therapeutically in a different, rapidly depigmenting model after loss of differentiated melanocytes resulted in 76% recovery of pigmentation. Treatment also prevented relevant T cells from populating mouse skin. In addition, ex vivo treatment of human skin averted the disease-related shift from quiescent to effector T cell phenotype. Thus, HSP70i DNA delivery may offer potent treatment opportunities for vitiligo.
    Science translational medicine 02/2013; 5(174):174ra28. · 7.80 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

anti-hsp65 antibody levels
 
anti-hsp70 antibodies correlate
 
anti-hsp70 antibody levels
 
anti-hsp70 IgG antibody levels
 
body mass index
 
C-reactive protein
 
CAD patients
 
carotis disease
 
cellular immune response
 
certain autoimmune diseases
 
certain risk factors
 
complement system
 
coronary atherosclerosis
 
healthy subjects
 
Heat shock proteins
 
human hsp70
 
immune system
 
lipid parameters
 
median level
 
severe coronary artery disease