CE44 - Biochimie du Vivant

Immunoglobulin G characterization for diagnosis of congenital diseases – IgName

Submission summary

Postnatal diagnosis of congenital toxoplamosis infection, caused by the parasite Toxoplasma gondii is imperative to ensure optimal medical care. Thus, the early identification of specific antibodies developed by the newborn is of crucial importance. This is a challenge because of the joint presence with maternal immunoglobulin G (IgG) in the serum of the newborn. The present proposal aims to identify newborn IgG that are specific for the pathogen. To achieve this goal, we will explore the individual signatures carried by the heavy chain of IgG and resulting from polymorphisms of several amino acids. We will use affinity purification to select specific IgG, adapted device to miniaturize these protocols and middle-down mass spectrometry for the proteogenomic characterization of these IgGs . Mapping of glycosylation of IgG will also be performed. Many scientific challenges will be overcome: (1) we will propose a workflow for the purification of pathogen-specific IgGs; (2) we will develop a proteolytic system to release the shortest discriminant sequences to identify peptide variants; (3) we will integrate the most recent updates of genomic information available in the public repository with dedicated proteomics and intermediary approaches in a proteogenomic strategy; (4) we will analyze the glycosylation profile in order to study a potential correlation with the specificity of IgG and their maternal or infant origin. We will use key samples that are already well characterized to validate our approach, and then apply it to paired samples of mothers (peripheral blood) and newborns (cord blood) derived from two existing cohorts in France and Benin focused on toxoplasmosis. The samples of interest are those taken in cases where the mother had a toxoplasmosis primary infection inducing seroconversion during pregnancy and where the newborn is suspected of having contracted the infection in utero. To be successful, the strategy will be optimized to achieve the sensitivity required to be directly compatible with the small amount of peripheral blood that can be collected from a neonate (maximum total serum volume 100 µL). This project will benefit from the expertise of complementary teams in immunological studies of congenital diseases and middle-down proteomics. It will be accompanied by three particularly adapted structures: the IRD, which coordinates the establishment of cohorts of interest, the ESPCI proteomics platform and in particular a high-resolution UVPD MS/MS mass spectrometer with a regional funding obtained in 2018, and the IPGG Labex for microfluidics. The two partners have been working together since 2011, which has been formalized by a collaborative research program between IRD and ESPCI. In the long term, this technological breakthrough will pave the way for many applications such as the diagnosis and monitoring of other congenital parasitic diseases (mainly Chagas disease), or more generally other infections of bacterial or viral origin, as well as other pathologies associated with autoimmune disorders such as insulin-dependent type 1 diabetes.

Project coordination

Joelle Vinh (Spectrométrie de Masse Biologique et Protéomique)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

SMBP Spectrométrie de Masse Biologique et Protéomique
MERIT MÈRE ET ENFANT EN MILIEU TROPICAL

Help of the ANR 307,600 euros
Beginning and duration of the scientific project: December 2019 - 42 Months

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