Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Authors: Mokuda et al.

Link to paper:

Journal/ Pre-Print: BioRxiv preprint

Tags:Cell Biology

Research Highlights 

1. Active rheumatoid arthritis samples express more ACE2 protein by immunohistochemistry and more gene expression by RT-qPCR compared to inactive samples.

2. IL-6 + IL-6Rα stimulation of rheumatoid arthritis fibroblast-like cells increases ACE2 expression, and might be inhibited by siRNA of STAT3


The paper does not directly address COVID-19, but shows IL-6 signalling through STAT3 can upregulate ACE2 in primary synovial fibroblast-like cells from rheumatoid arthritis patients. ACE2 protein is increased in active rheumatoid arthritis immunohistochemistry samples and gene expression is upregulated in active synovial tissues. IL-6 + IL-6Rα stimulation upregulates ACE2, supposedly in a STAT3-dependent manner. They propose the increased IL-6 in COVID-19 patients may increase ACE2 expression, but only demonstrate this in synovial cells from rheumatoid arthritis patients.

Impact for SARS-CoV2/COVID19 research efforts

Understand ACE2 expression in synovial tissues of rheumatoid arthritis patients

ACE2 is involved in the viral entry of SARS-CoV-2, this study observes ACE2 expression in RA (autoimmune disease) and by IL-6 (inflammatory cytokine).

Study Type

· In vitro study

· Tissue sections from RA patients

Strengths and limitations of the paper

Novelty: IL-6 upregulates ACE2 expression in the synovium.

Standing in the field: Rheumatoid arthritis drugs are already being investigated for COVID-19 treatment (e.g. anti-IL-6 tocilizumab).

No direct link between synovial ACE2 expression and COVID-19.

No direct clinical relevance of synovium in disease severity.

Appropriate statistics: ANOVA with post-hoc comparisons should be used in (C) and (D) where Student’s T-test was incorrectly used.

Viral model used: No viral model.

Translatability: Far from translatable. A link between synovium and COVID-19, or RA and COVID-19 should be made, or relevant cell type observed.

Main limitations: No direct use of, or relation to SARS-CoV-2 apart from ACE2.

No direct link of synovium to COVID-19 demonstrated.

Did not show STAT pathway phosphorylation or ACE2 protein expression upon stimulation (only RT-qPCR and ACE2).

Should increase n > 3; correct statistics might render results insignificant.