DNASE1L3 deficiency, new phenotypes and evidence for a transient type I interferon signaling

Risultato della ricerca: Meeting Abstractpeer review


Introduction: Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated to a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans.Objectives: Here, we report on four patients with pathogenic variations in DNASE1L3, including 2 previously undescribed causal variants, and expand the phenotype from SLE to vasculitis with gut involvement. To explore whether or not the interferon cascade was strongly and sustainably induced, Interferon stimulated genes (ISGs) expression was assessed for each patient. We also review previous reports highlighting the spectrum of DNASE1L3 deficiency.Methods: Identification of disease-causing variants was based on NGS sequencing in 3 out of 4 patients, and for one patient, coding regions of the DNASE1L3 gene were directly sequenced by Sanger sequencing. Type I interferon signature was determined using either quantitative reverse transcription polymerase chain reaction or nanostring technology, and serum IN-α2 concentrations was measured using simoa assay.Results: Disease in one patient was characterized by lupus nephritis and skin lesions, while two others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented with early-onset inflammatory bowel disease. Contrary to canonical type-I interferonopathies, we noticed a transient increase of ISGs in blood, which reverted to normal with disease remission.Conclusion: Reviewing previous reports, DNASE1L3-related disease appears to carry a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). DNASE1L3 deficiency may share the pathogenesiswith C1q deficiency by affecting efferocytosis, and this report suggests that interferon production is not directly driven by DNASE1L3 pathogenic variants.
Lingua originaleEnglish
pagine (da-a)155-156
Numero di pagine2
Stato di pubblicazionePublished - 2021

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.2700.2723???
  • ???subjectarea.asjc.2700.2745???


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