Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria.

Julie Bachmann,Setia Pramana,Felix O Akinbami,Peter Nilsson,Biobele J Brown,Wasiu A Ajetunmobi,Olugbemiro Sodeinde,Florence Burté,Samuel Omokhodion,Wuraola A Shokunbi,Adebola E Orimadegun,Francis Akinkunmi,Mathias Uhlén,Caroline Kampf,Jochen M Schwenk,Nathaniel K Afolabi,Mats Wahlgren,Ianina Conte,Yudi Pawitan,Delmiro Fernandez‐Reyes

doi:10.1371/journal.ppat.1004038

Abstract

Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.

Highlights

Human malaria is a life-threatening disease causing an estimated 655,000 deaths in 2010 [1]
The mortality rates have decreased during the last decade, deaths in Africa due to childhood malaria are still elevated with Plasmodium falciparum attributable to a third of the childhood deaths accounted in Nigeria [2]
Why do some malaria-infected children develop severe and lethal forms of the disease, while others only have mild forms? In order to try to find potential answers or clues to this question, we have here analyzed more than 1,000 different human proteins in the blood of more than 500 malaria-infected children from Ibadan in Nigeria, a holoendemic malaria region

Summary

Introduction

Human malaria is a life-threatening disease causing an estimated 655,000 deaths in 2010 [1]. The most common severe syndromes, i.e. cerebral malaria, severe malaria anemia or respiratory distress, have been widely investigated, many aspects of their pathogenesis remain elusive. It is yet unknown what predetermines which children are at risk of developing complications. It is known that increased micro-vascular congestion accompanies coma in cerebral malaria and the depth of coma is correlated to the extent of the sequestration of the pRBC [3]. In the case of severe malaria anemia, increased destruction of pRBC and non-pRBC, splenic sequestration of RBC and dyserythropoiesis contribute to anemia and free-heme-

Results

Discussion

Conclusion