Pathogenesis and treatment of idiopathic and rheumatoid arthritis-related interstitial pneumonia. The possible lesson from COVID-19 pneumonia

Rheumatoid arthritis (RA) is considered a systemic inflammatory disease marked by polyarthritis which affects the joints symmetrically, leading to progressive damage of the bone structure and eventually joint deformity. Lung involvement is the most prevalent extra-articular feature of RA, affecting 10–60% of patients with this disease. In this review, we aim to discuss the patterns of RA interstitial lung disease (ILD), the molecular mechanisms involved in the pathogenesis of ILD in RA, and also the therapeutic challenges in this particular extra-articular manifestation. The pathophysiology of RA-ILD has been linked to biomarkers such as anti-citrullinated protein antibodies (ACPAs), MUC5B mutation, Krebs von den Lungen 6 (KL-6), and other environmental factors such as smoking. Patients at the highest risk for RA-ILD and those most likely to advance will be identified using biomarkers. The hope is that finding biomarkers with good performance characteristics would help researchers better understand the pathophysiology of RA-ILD and, in turn, lead to the development of tailored therapeutics for this severe RA manifestation.

show abstract

“…Germs such as Proteus spp. and Porphyromonas gingivalis are thought to be involved in the pathogenesis of RA-ILD [ 13 , 14 ].…”

Section: Pathogenesismentioning

confidence: 99%

Novel Biomarkers, Diagnostic and Therapeutic Approach in Rheumatoid Arthritis Interstitial Lung Disease—A Narrative Review

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Some authors also suggest the inhibition of toll-like receptor 4 (TLR4) [48], which have been previously investigated as a possible therapeutic target for preventing lethal complications of some viral diseases [48]. The role of TLR4 in the pathogenesis of RA and RA-ILD has been demonstrated and its inhibition in experimental model showed to suppress the production of IL6, IL8, metalloproteinase-1 and vascular endothelial growth factor [49].…”

Section: Covid-19 Pneumonia and Ra-related Interstitial Lung Disease mentioning

confidence: 99%

Clinical management of patients with rheumatoid arthritis during the COVID-19 pandemic

Favalli

Maioli

Biggioggero

et al. 2021

Expert Review of Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…Virus-induced lung injury, immune response, and attempts at healing are central to the process of fibrogenesis (Ojo et al, 2020). Features of COVID-19 presents some common points with IPF and RA-ILD, typically characterized by a chronic progression over time and possibly complicated by acute exacerbation (Manfredi et al, 2020). Our data showed that LTBP2 expression was up-regulated in patients with IPF, RA-ILD and COVID-19-related PF.…”

Section: Discussionmentioning

confidence: 61%

Latent Transforming Growth Factor-β Binding Protein-2 Regulates Lung Fibroblast-to-Myofibroblast Differentiation in Pulmonary Fibrosis via NF-κB Signaling

Zou

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. The aberrantly activated lung myofibroblasts, predominantly emerging through fibroblast-to-myofibroblast differentiation, are considered to be the key cells in PF, resulting in excessive accumulation of extracellular matrix (ECM). Latent transforming growth factor-β (TGFβ) binding protein-2 (LTBP2) has been suggested as playing a critical role in modulating the structural integrity of the ECM. However, its function in PF remains unclear. Here, we demonstrated that lungs originating from different types of patients with PF, including idiopathic PF and rheumatoid arthritis-associated interstitial lung disease, and from mice following bleomycin (BLM)-induced PF were characterized by increased LTBP2 expression in activated lung fibroblasts/myofibroblasts. Moreover, serum LTBP2 was also elevated in patients with COVID-19-related PF. LTBP2 silencing by lentiviral shRNA transfection protected against BLM-induced PF and suppressed fibroblast-to-myofibroblast differentiation in vivo and in vitro. More importantly, LTBP2 overexpression was able to induce differentiation of lung fibroblasts to myofibroblasts in vitro, even in the absence of TGFβ1. By further mechanistic analysis, we demonstrated that LTBP2 silencing prevented fibroblast-to-myofibroblast differentiation and subsequent PF by suppressing the phosphorylation and nuclear translocation of NF-κB signaling. LTBP2 overexpression-induced fibroblast-to-myofibroblast differentiation depended on the activation of NF-κB signaling in vitro. Therefore, our data indicate that intervention to silence LTBP2 may represent a promising therapy for PF.

show abstract

Pathogenesis and treatment of idiopathic and rheumatoid arthritis-related interstitial pneumonia. The possible lesson from COVID-19 pneumonia

Cited by 13 publications

References 111 publications

Novel Biomarkers, Diagnostic and Therapeutic Approach in Rheumatoid Arthritis Interstitial Lung Disease—A Narrative Review

Novel Biomarkers, Diagnostic and Therapeutic Approach in Rheumatoid Arthritis Interstitial Lung Disease—A Narrative Review

Clinical management of patients with rheumatoid arthritis during the COVID-19 pandemic

Latent Transforming Growth Factor-β Binding Protein-2 Regulates Lung Fibroblast-to-Myofibroblast Differentiation in Pulmonary Fibrosis via NF-κB Signaling

Contact Info

Product

Resources

About