Affinity Proteomics Reveals Elevated Muscle Proteins in Plasma of Children with Cerebral Malaria

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.

The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations

“…All participating children from Ibadan were recruited under the direction of the Childhood Malaria Research Group (CMRG) at the Department of Pediatrics of the University College Hospital (UCH), Ibadan, Nigeria, as previously described (8)(9)(10)(11). Briefly, children were 6 months to 13 years of age.…”

Proteomic analysis of Plasmodium falciparum induced alterations in humans from different endemic regions of India to decipher malaria pathogenesis and identify surrogate markers of severity

“…Moreover, the intent of this study was to identify potential predictive and disease monitoring markers for severity in falciparum malaria. Comparative proteomic profiling of serum from healthy community controls and non-severe and severe falciparum malaria patients from different malaria endemic regions from India provided a plethora of information to complement the earlier similar proteomics studies reported on the African populations [10][11][12]20], and provided some novel mechanistic insights into the pathogenic mechanism for disease severity in P. falciparum infection (Fig. 3).…”

“…A series of studies over the past decade has provided valuable information regarding the proteomic alterations in human host in falciparum and vivax malaria [10][11][12]20,21]. In previously reported studies, differential abundance of multiple serum proteins including haptoglobin, serum amyloid A, serum albumin, apolipoprotein A-1, apolipoprotein E, alpha-2-macroglobulin, and vitronectin has been described in adults suffering from non-severe falciparum malaria [13,20] (Table 2).…”

“…Indepth analysis of the differential abundances of serum/plasma proteins during the febrile stage of the infection may help in identification of surrogate markers of infection and disease severity and can provide valuable information regarding disease pathogenesis and host immune responses [8,9]. A few previous studies have investigated the alterations in plasma proteome profiles in cerebral falciparum malaria in children from different endemic and holoendemic regions of Africa [10][11][12]. However, there is a dearth of similar proteomic analysis of severe falciparum malaria in Indian populations.…”

Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients

“…Decreased levels of AMFR found in plasma from osteoporosis patients may reflect a lower level of physical activity in osteoporotic patients, when considering that transcripts were abundant in skeletal muscle and mirroring a reduced turnaround in muscle proteins. In other recent studies on neuromuscular dystrophy 31 and childhood malaria 32, other muscle proteins have been detected in plasma as indicators of disease.…”