@article{fdi:010064845, title = {{I}mmunoglobulin response to {P}lasmodium falciparum {RESA} proteins in uncomplicated and severe malaria}, author = {{B}adaut, {C}. and {G}uyonnet, {L}{\'e}a and {M}ilet, {J}acqueline and {R}enard, {E}. and {D}urand, {R}. and {V}iwami, {F}. and {S}agbo, {G}. and {L}ayla, {F}. and {D}eloron, {P}hilippe and {B}onnefoy, {S}. and {M}igot {N}abias, {F}lorence}, editor = {}, language = {{ENG}}, abstract = {{B}ackground: {T}he three members of the ring-infected erythrocyte surface antigen ({RESA}) proteins family share high sequence homologies, which impair the detection and assignment to one or another protein of some pathogenic processes inherent to {P}lasmodium falciparum malaria. {T}he present study was intended to determine if the antibody and inflammatory responses of children living in a malaria-endemic area varied depending on the {RESA}-1, {RESA}-2 or {RESA}-3 proteins and the severity of the disease, two groups of severe and uncomplicated malaria cases being considered. {M}ethods: {T}wo synthetic peptides representing predicted {B} cell epitopes were designed per {RESA} protein, all located outside of the 3' and 5' repetition blocks, in order to allow an antibody detection specific of each member of the family. {R}ecombinant r{RESA}-1{B} and r{RESA}-3{B} proteins were also engineered. {T}wo groups of {B}eninese children admitted to hospital in 2009 for either uncomplicated or severe malaria were compared for their plasma levels of {I}g{G} specifically recognizing each recombinant {RESA} protein or synthetic peptide, and for their plasma inflammatory cytokine levels ({IFN}-gamma, {TNF}-alpha and {IL}-10), taking into account host and parasite genetic factors. {R}esults: {T}he absence of {I}g{G} cross-reactivity between r{RESA} proteins and their protein carrier as well as between each {RESA} peptide and a non-epitopic {RESA} control peptide validated the use of the engineered recombinant proteins and peptides for the measurement of plasma {I}g{G}. {T}aking into account age, fever duration and parasitaemia, a multiple logistic regression performed on children clustered according to their antibody responses' profiles concluded to an increased risk of severe malaria for {P}2 (representative of {RESA}-1) responders ({P} = 0.007). {I}ncreased {IL}-10 plasma levels were found in children harbouring multiclonal {P}. falciparum infections on the basis of the {T}1526{G} resa2 gene polymorphism ({P} = 0.004). {C}onclusions: {T}his study provided novel tools to dissect the seroreactivity against the three members of the {RESA} protein family and to describe its relation to protection against malaria. {I}t suggested the measurement of plasma antibodies raised against specific peptides to serve as predictive immunologic markers for disease severity. {L}astly, it reinforced previous observations linking the {T}1526{G} resa2 gene mutation to severe malaria.}, keywords = {{P}lasmodium falciparum ; severe malaria ; {R}ing-infected erythrocyte surface ; antigen ; {B} cell epitope ; {B}enin ; {BENIN}}, booktitle = {}, journal = {{M}alaria {J}ournal}, volume = {14}, numero = {}, pages = {art. 278 [13 p.]}, ISSN = {1475-2875}, year = {2015}, DOI = {10.1186/s12936-015-0799-8}, URL = {https://www.documentation.ird.fr/hor/fdi:010064845}, }