| Title: |
Quantification of human plasma metalloproteins in multiple sclerosis, ischemic stroke and healthy controls reveals an association of haptoglobin-hemoglobin complexes with age |
| Authors: |
Sarpong-Kumankomah, Sophia; Knox, Katherine B.; Kelly, Michael E.; Hunter, Gary; Popescu, Bogdan; Nichol, Helen; Kopciuk, Karen; Ntanda, Henry; Gailer, Jürgen |
| Contributors: |
Xu, Jian; Royal University Hospital Foundation |
| Source: |
PLOS ONE ; volume 17, issue 1, page e0262160 ; ISSN 1932-6203 |
| Publisher Information: |
Public Library of Science (PLoS) |
| Publication Year: |
2022 |
| Collection: |
PLOS Publications (via CrossRef) |
| Description: |
Advanced analytical methods play an important role in quantifying serum disease biomarkers. The problem of separating thousands of proteins can be reduced by analyzing for a ‘sub-proteome’, such as the ‘metalloproteome’, defined as all proteins that contain bound metals. We employed size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES) to analyze plasma from multiple sclerosis (MS) participants (n = 21), acute ischemic stroke (AIS) participants (n = 17) and healthy controls (n = 21) for Fe, Cu and Zn-metalloproteins. Using ANOVA analysis to compare the mean peak areas among the groups revealed no statistically significant differences for ceruloplasmin (p = 0.31), α 2 macroglobulin (p = 0.51) and transferrin (p = 0.31). However, a statistically significant difference was observed for the haptoglobin-hemoglobin (Hp-Hb) complex (p = 0.04), being driven by the difference between the control group and AIS (p = 0.012), but not with the MS group (p = 0.13), based on Dunnes test. A linear regression model for Hp-Hb complex with the groups now adjusted for age found no statistically significant differences between the groups (p = 0.95), but was suggestive for age (p = 0.057). To measure the strength of association between the Hp-Hb complex and age without possible modifications due to disease, we calculated the Spearman rank correlation in the healthy controls. The latter revealed a positive association (r = 0.39, 95% Confidence Interval = (-0.05, 0.83), which suggests that either the removal of Hp-Hb complexes from the blood circulation slows with age or that the release of Hb from red blood cells increases with age. We also observed that the Fe-peak corresponding to the Hp-Hb complex eluted ~100 s later in ~14% of all study samples, which was not correlated with age or disease diagnosis, but is consistent with the presence of the smaller Hp (1–1) isoform in 15% of the population. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1371/journal.pone.0262160 |
| Availability: |
https://doi.org/10.1371/journal.pone.0262160; https://dx.plos.org/10.1371/journal.pone.0262160 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.7D0146B5 |
| Database: |
BASE |