Actually, a previous research demonstrated a higher degree of cross-inhibition between antibodies generated against the D and the F allelic forms of MSP-1 [39]. IgG subclass analysis showed that IgG1 and IgG3 were the predominant subclasses for most of the antigens studied, consistent with previous studies [34,51,61]. in CM patients compared to healthy controls. Significantly lower levels of total IgG antibodies to the MSP-1f38, IgG1 levels to MSP-1d83, MSP-119 and MSP-636 and IgG3 levels to MSP-1f42 and MSP-722 were observed in CM patients as compared to MM patients. Conclusion These results suggest that there may be some dysregulation in the generation of antibody responses to some MSP antigens in CM patients and it is Telotristat worth investigating further whether perturbations of antibody responses in CM patients contribute to pathogenesis. Background One life-threatening complication of Plasmodium falciparum contamination is usually cerebral malaria (CM). This complex syndrome affects mainly young children (two to Telotristat six years old) in sub-Saharan Africa with an estimated incidence of 1 1.12 cases per 1,000 children per year and an estimated mortality of 18.6% [1]. In addition, a subset of CM survivors have an increased risk of developing persistent neurocognitive sequelae post-recovery [2-4] and reviewed in [5]. In Asia and South America, where the intensity of P. falciparum is usually much lower than in Africa, all age groups are at risk for CM [1,6-9]. The pathogenesis of CM is usually complex and it is still poorly understood as to why only a subset of patients develop CM. Various factors, such as sequestration of infected erythrocytes, and inflammatory cytokines and chemokines, have been postulated to play major functions in CM pathogenesis [10-17]. The role of antibodies in CM pathogenesis or protection Telotristat is not well comprehended. The merozoite surface protein (MSP)-1, a large multiprotein complex uncovered on the surface of merozoites, is one of the well characterized antigens of P. falciparum. During late schizogony, MSP-1 is usually proteolytically processed from its ~190 kDa precursor into four major cleavage products: p83, p30, p38, and p42 [18] designated as MSP-183, MSP-130, MSP-138 and MSP-142 respectively. During erythrocyte invasion, the MSP-142 fragment is usually further Telotristat cleaved into MSP-133 and MSP-119 which is essential for invasion (Physique ?(Figure1A)1A) [19]. The proteolytically processed MSP-1 appears to exist in association with the processed products of MSP-6 and MSP-7 (Physique ?(Figure1B)1B) [20-22]. Major biochemical and immunological parameters of this multipartite have been described recently [23]. Open in a separate window Physique 1 Schematic representation of the MSP-1 and MSP-1/MSP-6/MSP-7 complex antigens used in the study. The schematic representation of the MSP-1 protein is shown (A). The MSP-1 precursor protein (i) undergoes proteolytic cleavage into four subunits as shown (ii). The MSP-142 molecule is usually further cleaved to MSP-133 and MSP-119 (iii). A proposed model (adapted from [23]) demonstrating the interactions of MSP-1 protein with the MSP-636 and MSP-722 EDA molecules (B). The two allelic forms of MSP-183, MSP-130, MSP-138 and MSP-142 (D and F), in addition to MSP-636, MSP-722 and MSP-119, were expressed in E. coli and purified [49,50]. The purity of these Telotristat recombinant proteins was examined by using 12% SDS-PAGE followed by Coomassie staining (C). Molecular weight (MW) is shown in kDa. Humoral immune responses to MSP-1 protein subunits, especially, MSP-142 and MSP-119 fragments, are known to be protective against P. falciparum contamination and clinical malaria [24-33]. Antibodies specific for these antigens have been shown to inhibit both erythrocyte invasion and parasite growth in vitro [26,27]. In some studies, antibody responses to MSP-119 were correlated with clinical immunity to P. falciparum [29,30,34] and with reduced parasitaemia and fever [31]. In addition, presence of several T-cell epitopes within the MSP-142 fragment were identified [35] and these epitopes may provide T- helper function needed for the production of anti-MSP-1 antibodies. Studies of the msp-1 gene sequence obtained from different P. falciparum isolates demonstrate significant antigenic diversity comprising highly conserved, dimorphic and variable regions. There are two major allelic forms of MSP-1 belonging to either the K1, (as in the FCB-1 strain, here referred to as F allelic form) or the MAD20 (as in the 3D7 strain, here referred to as D allelic form) allelic families [36,37]. Therefore, one would postulate that naturally exposed individuals would mount immune responses to different fragments and allelic forms of MSP-1. However, only a few field studies have investigated humoral responses to both of these allelic forms of the four major subunits of MSP-1 and their associated proteins,.