SCID patients with ARTEMIS vs RAG deficiencies following HCT: increased risk of late toxicity in ARTEMIS-deficient SCID

Catharina Schuetz, Benedicte Neven, Christopher C Dvorak, Sandrine Leroy, Markus J Ege, Ulrich Pannicke, Klaus Schwarz, Ansgar S Schulz, Manfred Hoenig, Monika Sparber-Sauer, Susanne A Gatz, Christian Denzer, Stephane Blanche, Despina Moshous, Capucine Picard, Biljana N Horn, Jean-Pierre de Villartay, Marina Cavazzana, Klaus-Michael Debatin, Wilhelm FriedrichAlain Fischer, Morton J Cowan

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)


A subgroup of severe combined immunodeficiencies (SCID) is characterized by lack of T and B cells and is caused by defects in genes required for T- and B-cell receptor gene rearrangement. Several of these genes are also involved in nonhomologous end joining of DNA double-strand break repair, the largest subgroup consisting of patients with T(-)B(-)NK(+)SCID due to DCLRE1C/ARTEMIS defects. We postulated that in patients with ARTEMIS deficiency, early and late complications following hematopoietic cell transplantation might be more prominent compared with patients with T(-)B(-)NK(+)SCID caused by recombination activating gene 1/2 (RAG1/2) deficiencies. We analyzed 69 patients with ARTEMIS and 76 patients with RAG1/2 deficiencies who received transplants from either HLA-identical donors without conditioning or from HLA-nonidentical donors without or with conditioning. There was no difference in survival or in the incidence or severity of acute graft-versus-host disease regardless of exposure to alkylating agents. Secondary malignancies were not observed. Immune reconstitution was comparable in both groups, however, ARTEMIS-deficient patients had a significantly higher occurrence of infections in long-term follow-up. There is a highly significant association between poor growth in ARTEMIS deficiency and use of alkylating agents. Furthermore, abnormalities in dental development and endocrine late effects were associated with alkylation therapy in ARTEMIS deficiency.

Original languageEnglish
Pages (from-to)281-289
Number of pages9
Issue number2
Early online date21 Oct 2013
Publication statusPublished - 9 Jan 2014


  • B-Lymphocytes/immunology
  • DNA-Binding Proteins/deficiency
  • Endonucleases
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease/etiology
  • HLA Antigens/immunology
  • Hematopoietic Stem Cell Transplantation
  • Homeodomain Proteins/genetics
  • Humans
  • Lymphocyte Depletion
  • Male
  • Mutation
  • Nuclear Proteins/deficiency
  • Risk Factors
  • Severe Combined Immunodeficiency/complications
  • T-Lymphocytes/immunology
  • Transplantation Conditioning
  • Treatment Outcome


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