Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome

Autoimmune Cytopenia: Genetics and Pathophysiological Mechanism in Pediatric Evans Syndrome

Characterization of the genetic causes, and of the immunopathological clinical and biological manifestations in children with pediatric Evans syndrome included in a prospective national observational cohort of rare diseases.

Pediatric Evans syndrome (pES) is a rare and severe disease combining immunologic thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). French patients from the 30 hematologic pediatric centers are from 2004 included in a prospective national OBS'CEREVANCE cohort.

A first pilot study revealed a monogenic cause in 7/18 patients (40%) with mutations in the CTLA-4, LRBA, STAT3 GOF, and KRAS. TNGS or exome studies were performed between 2015 and 2018 inn 80 patients with pSE from the OBS'CEREVANCE cohort. This approach, combined with by immunophenotyping lymphocyte, identified a genetic cause of the disease in 26 patients (32%) (TNFRSF6, CTLA4, LRBA, STAT3 GOF, PIK3CD, RAG1, KRAS) and potential causal mutations in 18 other patients (22%), bringing the proportion of potential single gene cause to 76%.

The central hypothesis of this study is that most, if not all, cases of pSE are related to a monogenic or digenic cause, possibly with the intervention of genetic modifiers such as somatic mutations.

Inclusion Criteria:

• Patient registered in the French national prospective OBS'CEREVANCE cohort
• Diagnosis of pediatric Evans syndrome (PTI+AHAI)
• Age strictly under 18 years at the initial onset
• Child residing in metropolitan France and affiliated to a french health insurance system
• Free, informed, written and signed consent

Exclusion Criteria:

• Evans syndrome secondary to chemotherapy, bone marrow transplantation or organ transplantation.
• Refusal to participate from parents/patients