MSACL 2016 US Abstract

Longitudinal Measurement of Protein Biomarkers in Healthy Individuals and Elite Athletes

Leigh Anderson (Presenter)
SISCAPA Assay Technologies

Authorship: N. Leigh Anderson, Morteza Razavi, Terry W. Pearson
SISCAPA Assay Technologies, Inc., Box 53309, Washington DC 20009, USA

Short Abstract Precise, longitudinal measurement of protein biomarkers in dried-blood-spots (DBS) is an attractive option for providing preventative, personalized medicine at reasonable cost. Here we present the results of longitudinal measurement of 22 proteins in DBS samples collected from ‘healthy’ individuals and elite athletes. Unique ‘protein-fingerprints’ were defined for each individual to monitor various body functions. Of particular interest were a panel of proteins used to measure the extent of muscle damage in athletes as a result of training/competition. We are currently assessing the effectiveness of such personalized protein measurements in preventing severe muscle damage as a result of ‘over-training’.

Long Abstract

Longitudinal sample collection for establishing personal baselines can be achieved using dried blood spots (DBS). However, measuring proteins in DBS samples is difficult due to spot-to-spot volume and hematocrit variations. To address the latter problem, we previously presented an automated SISCAPA workflow that corrects for volume and hematocrit variations by normalizing the peak area ratio measurements based on a set of high abundance plasma proteins that are used to calculate the exact plasma volume in each DBS sample. Using this workflow, we were able to track physiological changes in acute phase proteins (e.g. CRP) caused by such events as a common cold. The high precision of the workflow also allowed us to detect more subtle day-to-day changes caused by changes in diet or exercise.

Here we report the results of a study in which we longitudinally monitored 22 proteins whose abundance spans 8 orders of magnitude both in ‘healthy’ individuals and in elite athletes representing the Brazilian national teams during the 2015 Pan American games. To analyze the data, we first established personal baselines by calculating the normal standard deviation for a given protein in each person. We then were able to analyze deviations from that baseline for each protein and correlate the changes with the contextual information we had for each sample (e.g. time of sample collection, exercise, diet, etc.). For instance, we observed that levels of anti-thrombin III and fibrinogen, two important coagulation factors in blood, fluctuate ‘seasonally’ and in an anti-correlated fashion.

The results indicate that the average levels of the proteins under study vary significantly from one individual to another. The highest degree of variation was observed in manose binding lectin (MBL) and immunoglobulin M (IgM). Moreover, we observed that the scale of the ‘normal’ biological variation for a given protein within an individual differs between subjects. Therefore, a unique ‘protein-fingerprint’ can be defined for each individual representing the normal range for different protein ‘panels’. Using this concept, we monitored various body functions in elite athletes during their training regimen and in some cases pre and post competition. Of particular interest were a panel of proteins used to measure the extent of muscle damage as a result of training/competition. We are currently assessing the effectiveness of such personalized protein measurements in preventing severe muscle damage as a result of ‘over-training’ in elite athletes.

Using ‘model systems’ such as the one explained for elite athletes, we strive to identify the best approach by which longitudinal measurement of proteins in DBS samples can be translated into actionable information.

References & Acknowledgements:

We thank Dr. L.C. Cameron and Dr. Adriana Bassini for providing us with DBS samples collected from Brazilian athletes during the 2015 Pan American games.

Financial Disclosure

IP Royalty: yes

IP Desc:Inventor of the SISCAPA technology

Planning to mention or discuss specific products or technology of the company(ies) listed above:

yes