Plasmodium falciparum and Schistosoma mansoni are often found in human coinfections, and cross-reactive antibodies to different components of the two parasites have been detected. In this work, we identified a cross-reactive S. mansoni gene product, referred to as SmLRR, that seems to belong to the leucine-rich repeat protein family. Comparative analysis of SmLRR revealed 57% similarity with a putative gene product encoded in the P. falciparum genome. Antibodies to SmLRR were found in experimental infections and in both S. mansoni-and P. falciparum-infected individuals. Correlative analysis of human anti-SmLRR responses in Kenya and Uganda suggested that malaria and schistosomiasis drive the immunoglobulin G3 (IgG3) and IgG4 isotypes, respectively, against SmLRR, suggesting that there is differential regulation of cross-reactive isotypes depending on the infection. In addition, the levels of anti-SmLRR IgG4, but not the levels of IgG3, correlated positively with the intensity of S. mansoni infection.
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