Protein characterization of the IgM triplet involved in the diagnosis of congenital toxoplasmosis

Congenital toxoplasmosis is a fetal infection resulting from the transplacental transmission of Toxoplasma gondii in mothers who seroconvert during pregnancy. Neonatal diagnosis has recently been improved through the identification by L’Ollivier et al. (2012) and Peyclit et al. (2023) of a pathognomonic marker for congenital toxoplasmosis: the IgM triplet, corresponding to three high molecular weight bands of 75, 90, and 100 kDa, respectively found on the mother-child immunoblot pair profile. This is a new concept, as these three IgM bands reflect an immune response targeting proteins involved in vertical transmission of T. gondii. These proteins may be T. gondii secreted or non-secreted effectors implicated in host cell invasion, immune modulation, and parasite virulence. In this study, immunoproteomic techniques allowed us to identify thirty-two relevant protein spots on immunoblot, including four specifically associated with the IgM triplet. Protein identification by LC-MS/MS revealed several T. gondii proteins as strong candidates for the IgM triplet. Each of these proteins is, directly or indirectly, involved in cellular invasion and may also play a role in transplacental transmission of T. gondii. Identifying these proteins opens several avenues of therapeutic research that could improve the management of congenital toxoplasmosis.