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Two patients with chronic mucocutaneous candidiasis caused by TRAF3IP2 deficiency.
J Allergy Clin Immunol. 2020 Dec 23;:
Authors: Shafer S, Yao Y, Comrie W, Cook S, Zhang Y, Yesil G, Karakoç-Aydiner E, Baris S, Cokugras H, Aydemir S, Kiykim A, Ozen A, Lenardo M
Abstract
BACKGROUND: TRAF3IP2 (Act1) is an adapter protein that interacts with IL-17R via its SEF/IL-17R (SEFIR) domain and coordinates two separate pro-inflammatory pathways following IL-17 cytokine stimulation.
OBJECTIVE: To elucidate the immunological consequences of TRAF3IP2 homozygous mutations to improve treatments for immunodeficiency patients with chronic mucocutaneous candidiasis.
METHODS: We describe two patients presenting with chronic mucocutaneous candidiasis that harbor biallelic nonsense mutations in TRAF3IP2. The cellular and molecular features of this genetic defect were assessed using in vitro cytokine assays and protein analysis.
RESULTS: We show the homozygous mutation causes complete loss of protein expression. We also show that the absence of TRAF3IP2 was associated with a defective response to combined IL-2/IL-25 (IL-17E) stimulation.
CONCLUSION: Failure to initiate normal signaling downstream of IL-17R engagement likely contributes to the patients’ recurrent fungal infections. These findings add to our molecular understanding of genetic defects affecting this critical pathway of anti-fungal immunity.
PMID: 33359359 [PubMed – as supplied by publisher]
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