Responses

Download PDFPDF
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
Compose Response

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Statement of Competing Interests

PLEASE NOTE:

  • A rapid response is a moderated but not peer reviewed online response to a published article in a BMJ journal; it will not receive a DOI and will not be indexed unless it is also republished as a Letter, Correspondence or as other content. Find out more about rapid responses.
  • We intend to post all responses which are approved by the Editor, within 14 days (BMJ Journals) or 24 hours (The BMJ), however timeframes cannot be guaranteed. Responses must comply with our requirements and should contribute substantially to the topic, but it is at our absolute discretion whether we publish a response, and we reserve the right to edit or remove responses before and after publication and also republish some or all in other BMJ publications, including third party local editions in other countries and languages
  • Our requirements are stated in our rapid response terms and conditions and must be read. These include ensuring that: i) you do not include any illustrative content including tables and graphs, ii) you do not include any information that includes specifics about any patients,iii) you do not include any original data, unless it has already been published in a peer reviewed journal and you have included a reference, iv) your response is lawful, not defamatory, original and accurate, v) you declare any competing interests, vi) you understand that your name and other personal details set out in our rapid response terms and conditions will be published with any responses we publish and vii) you understand that once a response is published, we may continue to publish your response and/or edit or remove it in the future.
  • By submitting this rapid response you are agreeing to our terms and conditions for rapid responses and understand that your personal data will be processed in accordance with those terms and our privacy notice.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

Other responses

  • Published on:
    Comment 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).
    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)...

    Show More
    Conflict of Interest:
    None declared.
  • Published on:
    Correspondence 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”
    • George N. Goulielmos, Professor in Human Molecular Genetics Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, School of Medicine, University of Crete, Her
    • Other Contributors:
      • Maria I. Zervou, Human Molecular Geneticist

    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
    (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...

    Show More
    Conflict of Interest:
    None declared.