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Article Abstract
We describe the first cases of germline biallelic null mutations in ARPC5, part of the Arp2/3 actin nucleator complex, in two unrelated patients presenting with recurrent and severe infections, early-onset autoimmunity, inflammation, and dysmorphisms. This defect compromises multiple cell lineages and functions, and when protein expression is reestablished in-vitro, the Arp2/3 complex conformation and functions are rescued. As part of the pathophysiological evaluation, we also show that interleukin (IL)-6 signaling is distinctively impacted in this syndrome. Disruption of IL-6 classical but not trans-signaling highlights their differential roles in the disease and offers perspectives for therapeutic molecular targets.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287756 | PMC |
| http://dx.doi.org/10.1038/s41467-023-39272-0 | DOI Listing |
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Article Synopsis
- The article discusses the discovery of germline biallelic null mutations in the ARPC5 gene, affecting the Arp2/3 actin nucleator complex, in two patients with severe recurrent infections, early-onset autoimmunity, and other health issues.
- The mutations lead to compromised functions across multiple cell types, but restoring protein expression in vitro can rescue the complex's conformation and functions.
- The study reveals that IL-6 signaling is uniquely affected, with important distinctions between classical and trans-signaling pathways, suggesting potential therapeutic targets for treatment.