Proteomic Analysis of Eccrine Sweat: Implications for the Discovery of Schizophrenia Biomarker Proteins

Abstract

Liquid chromatography tandem mass spectrometry (LC-MS/MS) and multiple reaction monitoring mass spectrometry (MRM-MS) proteomics analyses were performed on eccrine sweat of healthy controls, and the results were compared with those from individuals diagnosed with schizophrenia (SZ). This is the first large scale study of the sweat proteome. First, we performed LC-MS/MS on pooled SZ samples and pooled control samples for global proteomics analysis. Results revealed a high abundance of diverse proteins and peptides in eccrine sweat. Most of the proteins identified from sweat samples were found to be different than the most abundant proteins from serum, which indicates that eccrine sweat is not simply a plasma transudate, and may thereby be a source of unique disease-associated biomolecules. A second independent set of patient and control sweat samples were analyzed by LC-MS/MS and spectral counting to determine qualitative protein differential abundances between the control and disease groups. Differential abundances of selected proteins, initially determined by spectral counting, were verified by MRM-MS analyses. Seventeen proteins showed a differential abundance of approximately two-fold or greater between the SZ pooled sample and the control pooled sample. This study demonstrates the utility of LC-MS/MS and MRM-MS as a viable strategy for the discovery and verification of potential sweat protein disease biomarkers.

The detection and measurement of interleukin-6 in venous and capillary blood samples, and in sweat collected at rest and during exercise

“…In addition, we have shown that IL-6 does not appear in sweat in concentrations similar to, or even above that of plasma, counter to previous reports (Cizza et al 2008;Marques-Deak et al 2006). Therefore, in agreement with previous proteomic analysis of sweat (Raiszadeh et al 2012), it is unlikely that sweat acts as a plasma transudate, at least in the case of IL-6.…”

“…Finally, sweat is known to contain a number of protease enzymes (Baechle et al 2006;Horie et al 1986) and protease inhibitors (Park et al 2011;Raiszadeh et al 2012). It is possible that during the 40 minute main collection period, these enzymes may be responsible for degrading IL-6, rendering it undetectable by ELISA.…”

“…However, in agreement with Raiszadeh et al, the present data do not support the notion that IL-6 is present in sweat in detectable levels and we suggest that measurement of IL-6 in sweat is not a valid or reliable measurement of systemic IL-6. Moreover, of 180 proteins identified in sweat, only albumin, zinc α2 glycoprotein, gelsolin, apolipoprotein D and clusterin 1 were present in both sweat and plasma (Raiszadeh et al 2012), indicating that future work aimed at using sweat as a potential vehicle for biomarkers or disease should focus on these proteins, as they have already been linked to a number of diseases and pathological conditions (Ceperuelo-Mallafré et al 2009;Dubois et al 2010;Hassan et al 2008;Mracek et al 2011;Rydén et al 2012;Yang et al 2013). …”

Sweat lipid mediator profiling: a noninvasive approach for cutaneous research

“…While several proteomic analyses of sweat have been reported (7,8), only five attempts at metabolomic analyses of sweat have been described. High-resolution nuclear magnetic resonance spectroscopy of sweat suggested the presence of several amino acids and lipid-associated groups (5,9).…”

Circulating biomarkers in schizophrenia: a proteomics perspective

“…Using such methods total populations of peripheral blood mononuclear cells (PBMC), specific lymphocytes subpopulations as T-cells (both stimulated or unstimulated), or red blood cells (RBC) obtained from the blood stream of SCZ patients have already been studied. [41,85,86] One study using saliva [87] and another using sweat [88] have already been performed in the context of SCZ proteomics.…”