Proteomics discovers link between muscle damage and cerebral malaria

Main Point:

Malaria-related complications remain a major cause of death for children in many parts of the world. Why some children develop these complications while others don’t is still not understood.

Published in:

PLOS Pathogens

Study Further:

A multidisciplinary group of scientists and clinicians under the direction of Peter Nilsson (SciLifeLab and KTH, Sweden), Mats Wahlgren (Karolinska Institutet, Sweden), Delmiro Fernandez-Reyes (Brighton & Sussex Medical School, UK) and Olugbemiro Sodeinde (College of Medicine, University of Ibadan, Nigeria), report results of a systematic proteomics approach to the question in PLOS Pathogens. They compared proteins in the blood of uninfected children with those in the blood of infected ones, and also proteins in blood from children with different severe malaria syndromes with proteins in blood from uncomplicated cases.

The researchers analyzed over 1000 proteins in more than 700 children. To make the study more rigorous, the samples were divided into “discovery” and “verification” sets, and only associations that were found in both were reported. There were 41 proteins that could distinguish between malaria patients and uninfected children from the same community. Most of these were components of the inflammatory response.

The researchers also found proteins that were specific to the two most deadly complicated malaria syndromes in children, namely severe malaria anemia and cerebral malaria. For both, combinations of proteins, so-called “signatures”, could identify the specific syndrome with high accuracy.

For cerebral malaria, the researchers found that a group of muscle-specific proteins was present in the children’s blood, suggesting that muscle cells are damaged. At least some of that damage might be associated with coma, which occurs in cerebral malaria but also in other diseases like meningitis.

The researchers conclude that their study could “provide key elements toward the discovery of distinct mechanisms in the human response to malaria infection between the two most fatal syndromes of childhood malaria” and that muscle-specific proteins in plasma might be “potential indicators of cerebral malaria”.

Reference:

Bachmann J, Burté F, Pramana S, Conte I, Brown BJ, et al. (2014) Affinity Proteomics Reveals Elevated Muscle Proteins in Plasma of Children with Cerebral Malaria. PLoS Pathog 10(4): e1004038. doi:10.1371/journal.ppat.1004038, http://dx.plos.org/10.1371/journal.ppat.1004038

Contact:

Peter Nilsson, e-mail: peter.nilsson@scilifelab.se, phone: +46.8524.81418

Delmiro Fernandez-Reyes, e-mail: D.Fernandez-Reyes@bsms.ac.uk, phone: +44.7956.661869

Mats Wahlgren, e-mail: mats.wahlgren@ki.se, phone: +46.7055.61246

Olugbemiro Sodeinde, e-mail: o.sodeinde@doctors.org.uk

Authors and Affiliations:

Julie Bachmann, KTH-Royal Institute of Technology, Sweden

Florence Burte, Medical Research Council National Institute for Medical Research, United Kingdom

Setia Pramana, Karolinska Institutet, Sweden

Ianina Conte, Medical Research Council National Institute for Medical Research, United Kingdom

Biobele J. Brown, University of Ibadan, University College Hospital, Nigeria

Adebola E. Orimadegun, University of Ibadan, University College Hospital, Nigeria

Wasiu A. Ajetunmobi, University of Ibadan, University College Hospital, Nigeria

Nathaniel K. Afolabi, University of Ibadan, University College Hospital, Nigeria

Francis Akinkunmi, University of Ibadan, University College Hospital, Nigeria

Samuel Omokhodion, University of Ibadan, University College Hospital, Nigeria

Felix O. Akinbami, University of Ibadan, University College Hospital, Nigeria

Wuraola A. Shokunbi, University of Ibadan, University College Hospital, Nigeria

Caroline Kampf, Uppsala University, Sweden

Yudi Pawitan, Karolinska Institutet, Sweden

Mathias Uhle, KTH-Royal Institute of Technology, Sweden

Olugbemiro Sodeinde, Medical Research Council National Institute for Medical Research, United Kingdom; University of Ibadan, University College Hospital, Nigeria

Jochen M. Schwenk, KTH-Royal Institute of Technology, Sweden

Mats Wahlgren, Karolinska Institutet, Sweden

Delmiro Fernandez-Reyes, Medical Research Council National Institute for Medical Research, United Kingdom; University of Ibadan, University College Hospital, Nigeria; Brighton & Sussex Medical School, United Kingdom

Peter Nilsson, KTH-Royal Institute of Technology, Sweden

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