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Journal Articles Blood Year : 2019

Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes

1 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
2 CIC Bordeaux
3 CEREVANCE - Centre de Référence National des Cytopénies Auto-immunes de l'Enfant
4 CHU Trousseau [APHP]
5 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
6 Hôpital Necker - Enfants Malades [AP-HP]
7 Equipe Inserm U1163 - The Clinical Bioinformatics laboratory
8 SFR Necker - UMS 3633 / US24 - Structure Fédérative de Recherche Necker
9 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
10 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
11 Service d'hématologie pédiatrique
12 UMR AGAP - Amélioration génétique et adaptation des plantes méditerranéennes et tropicales
13 HCL - Hospices Civils de Lyon, Departement de Neurologie
14 Service d'Immuno-Hémato-Oncologie Pédiatrique
15 CHU Dijon
16 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
17 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
18 CHU Nantes - Centre Hospitalier Universitaire de Nantes
19 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
20 CHU Clermont-Ferrand
21 IMRB - Institut Mondor de Recherche Biomédicale
22 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
23 Hôpital Arnaud de Villeneuve [CHRU Montpellier]
24 CHU de Poitiers - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
25 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
26 Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris]
27 Collège de France - Chaire Médecine expérimentale (A. Fischer)
Sylvain Hanein
  • Function : Author
  • PersonId : 890853
Vincent Barlogis
Eric Dore
  • Function : Author


Evans syndrome (ES) is a rare severe autoimmune disorder characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. In most cases, the underlying cause is unknown. We sought to identify genetic defects in pediatric ES (pES), based on a hypothesis of strong genetic determinism. In a national, prospective cohort of 203 patients with early-onset ES (median [range] age at last follow-up: 16.3 years ([1.2-41.0 years]) initiated in 2004, 80 nonselected consecutive individuals underwent genetic testing. The clinical data were analyzed as a function of the genetic findings. Fifty-two patients (65%) received a genetic diagnosis (the M+ group): 49 carried germline mutations and 3 carried somatic variants. Thirty-two (40%) had pathogenic mutations in 1 of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS), whereas 20 patients (25%) carried probable pathogenic variants in 16 genes that had not previously been reported in the context of autoimmune disease. Lastly, no genetic abnormalities were found in the remaining 28 patients (35%, the M- group). The M+ group displayed more severe disease than the M- group, with a greater frequency of additional immunopathologic manifestations and a greater median number of lines of treatment. Six patients (all from the M+ group) died during the study. In conclusion, pES was potentially genetically determined in at least 65% of cases. Systematic, wide-ranging genetic screening should be offered in pES; the genetic findings have prognostic significance and may guide the choice of a targeted treatment.
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Dates and versions

inserm-02439240 , version 1 (14-01-2020)



Jérôme Hadjadj, Nathalie Aladjidi, Helder Fernandes, Guy Leverger, Aude Magérus-Chatinet, et al.. Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes. Blood, 2019, 134 (1), pp.9-21. ⟨10.1182/blood-2018-11-887141⟩. ⟨inserm-02439240⟩
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