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- Published on: 2 October 2024
- Published on: 30 September 2024
- Published on: 2 October 2024Comment on editorial ‘Human hypofunctional NCF1 variants promote pulmonary fibrosis in the bleomycin-induced mouse model and patients with systemic sclerosis via expansion of SPP1+ monocytes-derived macrophages?’
The recently published paper by Yuan et al (1) convincingly show that NCF1 polymorphism is a major genetic cause of both diffuse cutaneous systemic sclerosis and lung fibrosis. The human association studies were confirmed in a single nucleotide polymorphism (SNP) knockin mouse. The description how the NCF1 polymorphism were discovered is however not correct. It is said that “We previously identified a hypofunctional variant (p.R90H) in neutrophil cytosolic factor 1 (NCF1), encoding a regulatory subunit of phagocyte NADPH oxidase 2 (NOX2), associated with robust risk of multiple autoimmune diseases including systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS) and rheumatoid arthritis (RA).” (2).
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In fact the single nucleotide polymorphism (NCF1-339) leading to amino acid replacement of arginine to histidine at position 90 (R90H) was published by Olsson et al already 2012 (3). Importantly, this paper was built on positional cloning of NCF1 as the major underlying gene controlling autoimmune arthritis in rats (4). Based on this discovery, studies on copy number variation and sequencing of all functional exons of human NCF1 lead to identification of several SNPs leading to amino acid replacements(3). One of them was R90H, which lowered reactive oxygen species response in transfected COS cells. Based on this discovery both Olsson et al and Zhang et al independently found that the R90H variant was strongly associated with systemic lupus erythematosus (2, 5)...Conflict of Interest:
None declared. - Published on: 30 September 2024Correspondence on “Human hypofunctional NCF1 variants promote pulmonary fibrosis in the bleomycin-induced mouse model and patients with systemic sclerosis via expansion of SPP1+ monocytes-derived macrophages” by “Yuan et al”
We read with great interest the article by Yuan et al on “Human hypofunctional NCF1 variants promote pulmonary fibrosis in the bleomycin-induced mouse model and patients with systemic sclerosis via expansion of SPP1+ monocytes-derived macrophages” [1] , focusing on the assessment of the role of a systemic lupus erythematosus (SLE) causal hypofunctional variant, the neutrophil cytosolic factor 1
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(NCF1)-p.Arg90His (p.R90H) substitution, in systemic sclerosis (SSc) [1] . In the framework of this article, authors conducted an elegant study using case–control cohorts as well as bleomycin-induced mouse models, both wild-type and knock-in.
Yuan et al nicely placed NCF1 - p. Arg90His polymorphism in a functional context, concluding that low NCF1 activity increases the risk for the development of diffuse cutaneous (dc) SSc and lung fibrosis, thus contributing to the severity of lung fibrosis in both BLM-treated mice and patients with SSc [1] . Notably, the amino acid substitution of arginine to histidine at position #90 of NCF1 protein that represents a subunit of NADPH oxidase, concerns a PX domain, which plays an important role in the membrane binding [2] and, in humans, it was found to lead to a reduced function of NADPH oxidase 2 . Of note, the p. Arg90His variant of NCF1 gene has been also associated, apart from SLE [3,4] , with rheumato...Conflict of Interest:
None declared.