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Inborn Errors of Immunity caused by defects of the DNA damage response pathways
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  • Benjamin Fournier,
  • Nizar Mahlaoui,
  • Despina Moshous,
  • Jean-Pierre DE VILLARTAY
Benjamin Fournier

Corresponding Author:[email protected]

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Nizar Mahlaoui
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Despina Moshous
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Several inborn errors of immunity are caused by defects in the general DNA repair machinery as exemplified by the T-B- RS-SCID condition owing to impaired resolution of programmed DNA double strands breaks introduced by RAG1/2 during V(D)J recombination. The genome instability generally associated with these conditions results in an increased propensity to develop malignancies requiring genotoxic based anti-cancer treatments. Moreover, the extent of immune deficiency often calls for hematopoietic stem cell transplantation as a definitive treatment, thus also demanding genotoxic based conditioning regimen prior to transplantation. In both cases, the underlying general DNA repair defects may result in catastrophic iatrogenic consequences. It is therefore of paramount importance to assess the functionality of the DNA repair apparatus prior to any genotoxic treatment when the exact molecular cause of the disease is unknown. For this purpose, two simple assays can be used on patient’s derived peripheral blood lymphocytes. 1) The PROMIDISα biomarker, based on the next generation sequencing analysis of the TCRα will highlight specific signatures of DNA repair deficiencies. 2) Direct analysis of the sensitivity of peripheral lymphocytes to ionizing radiations will formally identify patients at risk to develop toxicity towards genotoxic based treatments.
04 Mar 2022Submitted to Pediatric Allergy and Immunology
08 Mar 2022Reviewer(s) Assigned
09 Apr 2022Review(s) Completed, Editorial Evaluation Pending
13 Apr 2022Editorial Decision: Revise Minor
25 May 20221st Revision Received
26 May 2022Review(s) Completed, Editorial Evaluation Pending
30 May 2022Editorial Decision: Accept