Analysis of serum heat shock protein 70 (HSPA1A) concentrations for diagnosis and disease activity monitoring in patients with rheumatoid arthritis

Abstract

Heat shock proteins (HSPs) have been repeatedly implicated in the pathogenesis of rheumatoid arthritis (RA). The authors aimed to study applicability of heat shock protein 70 (HSPA1A) serum levels as a diagnostic factor and a severity indicator in patients with RA and to quantify cut-off point that predicts status of RA with highest specificity. A total of 76 patients with RA and 36 healthy adults were studied in this case-control analysis. Patients had a higher HSPA1A level than the control group (0.78 ± 0.13 vs. 0.12 ± 0.02 ng/mL, p = 0.006), irrespective of presence of absence of rheumatoid factor or anti-citrullinated cyclic peptide. Next, diagnostic accuracy of the HSPA1A in diagnosis of RA was evaluated (area under curve 0.71; p < 0.05). HSPA1A predicted status of having RA in levels above 0.42 ng/mL with more than 90 % specificity. In addition to diagnostic value, HSPA1A can distinguish between high disease activity (1.66 ± 0.75 ng/mL) and low (0.49 ± 0.1 ng/mL), moderate (0.52 ± 0.12 ng/mL), or remission phase (0.48 ± 0.11 ng/mL). Moreover, patients in remission still had a higher HSPA1A level compared to normal subject (0.48 ± 0.11 vs. 0.12 ± 0.02 ng/mL, p < 0.05). Our results showed that serum HSPA1A could be implemented as a specific tool to facilitate diagnosis and monitoring disease activity in patients with rheumatoid arthritis.

A comparison of two commercially available ELISA methods for the quantification of human plasma heat shock protein 70 during rest and exercise stress

“…eHSP70 stimulates neutrophil microbiocidal activity (Ortega et al 2006), chemotaxis (Ortega et al 2009) and induces cytokine production via a CD14-mediated pathway (Asea 2006), thereby promoting innate immune activation (Krause et al 2015). Elevated resting concentrations of eHSP70 has been positively correlated with insulin resistance (Krause et al 2015) and disease progression in auto-immune (Luo et al 2008) and inflammatory diseases (Schick et al 2004;Najafizadeh et al 2015). Therefore, eHSP70 may be a useful biomarker when monitoring the progression of diseases in which low-grade inflammation plays a role (Rodrigues- Krause et al 2012), such as sarcopenia (Ogawa et al 2012), rheumatoid arthritis (Najafizadeh et al 2015), diabetes (Krause et al 2015) and obesity (Chung et al 2008).…”

“…Elevated resting concentrations of eHSP70 has been positively correlated with insulin resistance (Krause et al 2015) and disease progression in auto-immune (Luo et al 2008) and inflammatory diseases (Schick et al 2004;Najafizadeh et al 2015). Therefore, eHSP70 may be a useful biomarker when monitoring the progression of diseases in which low-grade inflammation plays a role (Rodrigues- Krause et al 2012), such as sarcopenia (Ogawa et al 2012), rheumatoid arthritis (Najafizadeh et al 2015), diabetes (Krause et al 2015) and obesity (Chung et al 2008). The balance between the anti-inflammatory action of iHSP70 and pro-inflammatory action eHSP70 may determine the outcome (induction or attenuation of inflammation) during disease progression, in response to a treatment, or following an exercise bout (Krause et al 2015).…”

“…In many studies, the determination of basal eHSP70 has proven to be problematic (Ogawa et al 2012;Lee et al 2014a, b;Najafizadeh et al 2015) with no consensus normative data for resting eHSP70 reported to date. Sample handling considerations (e.g.…”

“…Additionally, EDTA is recommended for use over heparin as higher resting concentrations are derived (Whitham and Fortes 2006). Despite the recommendation to use EDTA plasma for eHSP70 determination (Whitham and Fortes 2006), multiple studies have attempted to quantify eHSP70 in serum for a range of conditions, with varied results (Dulin et al 2010;Najafizadeh et al 2015).…”

The lost correlation between heat shock protein 70 (HSPA1A) and plasminogen activator inhibitor-1 in patients with type 2 diabetes and albuminuria

“…Inducible HSPs are highly upregulated by heat shock factors (HSF) under stressful conditions to serve their protective roles. Extracellular levels of HSPs are increased in several diseases (Abe et al 2004;Najafizadeh et al 2015;Son et al 2015). including diabetic nephropathy (Morteza et al 2013b).…”