Study on primary immunodeficiencies & EBV- induced HL

Content Since more than a century, numerous observations have confirmed the key role of the immune system in the defense against cancers. The Epstein Barr virus (EBV) is associated with the development of lymphoproliferative disorders including B-cell lymphomas such as Hodgkin’s lymphoma (HL). Several pediatric forms of mendelian susceptibility to EBV infection leading to B-cell lymphomas have been recently identified. Studies of these primary immunodeficiencies allowed the discovery of factors and pathways involved the immune response against EBV, and more generally in the immune-surveillance of lymphomas. Our current hypothesis is that germinal mutations affecting the immune response could be responsible of pediatric forms of lymphoma. Until now 56 pediatric patients with B-cell lymphoproliferative disorders including 30 cases of HL have been recruited from pediatric clinical departments from French Hospitals. Patients and their relative were analyzed by whole exome sequencing (WES) to identify the genetic variations possibly contributing in the appearance of lymphoma in these patients. For patients diagnosed with Hodgkin lymphoma (HL), all were below 10 years old. Preliminary analyses of WES data identified relevant germinal genetic variations in 20% of cases. These mutations will be studied to understand their effect on the immune response and the lymphomagenesis. It is expected that this work will provide new insights into the pathophysiology of pediatric B lymphomas in particular Hodgkin’s lymphoma, including tools for the molecular and genetic diagnosis of these conditions.

• References

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