AB0007 Shared genetic predisposition in rheumatoid arthritis–interstitial lung disease and familial pulmonary fibrosis

Juge, P.-A.; Borie, R.; Kannengiesser, Caroline; Gazal, Steven; Revy, Patrick; Wémeau-Stervinou, Lidwine; Debray, Marcel; Ottaviani, Stefania; Marchand-Adam, S.; Nathan, Nadia; Thabut, Gabriel; Richez, Christophe; Nunès, Hilario; Callebaut, Isabelle; Justet, A.; Richette, Pascal; Lioté, H.; Allanore, Yannick; Sand, Olivier; Dromer, C; Rm, Flipo; Clément, Annick; Sibilia, Jean; Coustet, Baptiste; Cottin, Vincent; Mc, Boissier; Wallaert, B.; Schaeverbeke, T.; Florence, D.; Frazier, Aline; Ménard, Christelle; Soubrier, Martin; Saidenberg, N.; Valeyre, Dominique; Amselem, Serge; Boileau, Cathérine; Crestani, Bruno; Dieudé, Philippe

doi:10.1136/annrheumdis-2017-eular.5237

Cited by 11 publications

(5 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to familial IPF patients, data from exome-sequencing revealed the presence of TTR, RTL1, PARN, or SFTPC mutations in RA-ILD patients, indicating the contribution of IPF-linked genes in RA-ILD susceptibility (26). In addition to common genetic features, RA-ILD and IPF patients have overlapping clinical features, such as older age, and higher occurrence in males and in cigarette smokers (27,28).…”

Section: Geneticsmentioning

confidence: 82%

Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations

et al. 2021

View full text Add to dashboard Cite

Connective tissue disease (CTD) related interstitial lung disease (CTD-ILD) is one of the leading causes of morbidity and mortality of CTD. Clinically, CTD-ILD is highly heterogenous and involves rheumatic immunity and multiple manifestations of respiratory complications affecting the airways, vessels, lung parenchyma, pleura, and respiratory muscles. The major pathological features of CTD are chronic inflammation of blood vessels and connective tissues, which can affect any organ leading to multi-system damage. The human lung is particularly vulnerable to such damage because anatomically it is abundant with collagen and blood vessels. The complex etiology of CTD-ILD includes genetic risks, epigenetic changes, and dysregulated immunity, which interact leading to disease under various ill-defined environmental triggers. CTD-ILD exhibits a broad spectra of clinical manifestations: from asymptomatic to severe dyspnea; from single-organ respiratory system involvement to multi-organ involvement. The disease course is also featured by remissions and relapses. It can range from stability or slow progression over several years to rapid deterioration. It can also present clinically as highly progressive from the initial onset of disease. Currently, the diagnosis of CTD-ILD is primarily based on distinct pathology subtype(s), imaging, as well as related CTD and autoantibodies profiles. Meticulous comprehensive clinical and laboratory assessment to improve the diagnostic process and management strategies are much needed. In this review, we focus on examining the pathogenesis of CTD-ILD with respect to genetics, environmental factors, and immunological factors. We also discuss the current state of knowledge and elaborate on the clinical characteristics of CTD-ILD, distinct pathohistological subtypes, imaging features, and related autoantibodies. Furthermore, we comment on the identification of high-risk patients and address how to stratify patients for precision medicine management approaches.

show abstract

Section: Geneticsmentioning

confidence: 82%

Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Consistent with multiple studies ( 33 , 34 ), the association of RA-ILD with older age and male sex is demonstrated in this study. Older age is associated with RA-ILD suggesting that immunosenescence and telomere shortening may be linked with RA-ILD risk ( 35 ). Notably, it seems somewhat paradoxical that RA is more prevalent in females than males, with a female-to-male sex ratio ranging from 4:1 to less than 2:1 in younger and older patients respectively ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Serum CHI3L1 as a biomarker of interstitial lung disease in rheumatoid arthritis

Yu,

Liu,

Deng

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

BackgroundInterstitial lung disease (ILD) is a relatively prevalent extra-articular manifestation of rheumatoid arthritis (RA) and contributes to significant morbidity and mortality. This study aimed to analyze the association between chitinase-3 like-protein-1(CHI3L1) and the presence of RA-ILD.MethodsA total of 239 RA patients fulfilling the American Rheumatism Association (ACR) 1987 revised criteria were enrolled and subclassified as RA-ILD and RA-nILD based on the results of high-resolution computed tomography scans (HRCT) of the chest. The disease activity of RA was assessed by Disease Activity Score for 28 joints (DAS28) and categorized as high, moderate, low, and remission. Chemiluminescence immunoassays were applied to determine the serum levels of CHI3L1. Univariate analysis was performed and the receiver operating characteristics (ROC) curves were plotted to evaluate the correlation between RA-ILD and CHI3L1.ResultsAmong the eligible RA patients studied, 60 (25.1%) patients were diagnosed with RA-ILD. Compared with RA-nILD, RA patients with ILD had significantly higher median age (median [IQR], 68.00 [62.00-71.75] vs 53.00 [40.00-63.00], p<0.001) and a higher proportion of males (21 (35.0%) vs 30 (16.8%), p=0.003). Notably, differences in DAS28 scores between the two groups were not observed. The serum level of CHI3L1 was significantly higher in RA-ILD patients (median [IQR], 69.69 [44.51-128.66] ng/ml vs 32.19 [21.63-56.99] ng/ml, p<0.001). Furthermore, the areas under the curve (AUC) of CHI3L1 attained 0.74 (95% confidence interval [CI], 0.68-0.81, p<0.001) in terms of identifying patients with RA-ILD from those without ILD. Similar trends were seen across the spectrum of disease activity based on DAS28-ESR.ConclusionOur findings of elevated serum CHI3L1 levels in RA-ILD patients suggest its possible role as a biomarker to detect RA-ILD noninvasively.

show abstract

“…It is estimated that approximately 30% of RA patients have subclinical ILD, as shown by high-resolution computerized tomography (HRCT) scans [ 76 ]. Although the exact pathogenesis of ILD in RA remains unclear [ 75 , 76 , 77 , 78 ], smoking, male gender, older age, high titers of ACPA, disease duration, and positivity of the Human leukocyte antigen (HLA)-DR4 were probable risk factors for RA-ILD [ 78 , 79 , 80 , 81 , 82 ]. A study of the Western population revealed the MUC5B promoter variant rs35705950 as a genetic risk factor for developing RA-ILD, particularly in those with the usual interstitial pneumonia (UIP) pattern [ 83 ].…”

Section: Etiopathogenesis Of Ra and Its Comorbiditiesmentioning

confidence: 99%

The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review

Chen,

Tang,

Chen

2024

IJMS

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by chronic synovitis and the progressive destruction of cartilage and bone. RA is commonly accompanied by extra-articular comorbidities. The pathogenesis of RA and its comorbidities is complex and not completely elucidated. The assembly of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activates caspase-1, which induces the maturation of interleukin (IL)-1β and IL-18 and leads to the cleavage of gasdermin D with promoting pyroptosis. Accumulative evidence indicates the pathogenic role of NLRP3 inflammasome signaling in RA and its comorbidities, including atherosclerotic cardiovascular disease, osteoporosis, and interstitial lung diseases. Although the available therapeutic agents are effective for RA treatment, their high cost and increased infection rate are causes for concern. Recent evidence revealed the components of the NLRP3 inflammasome as potential therapeutic targets in RA and its comorbidities. In this review, we searched the MEDLINE database using the PubMed interface and reviewed English-language literature on the NLRP3 inflammasome in RA and its comorbidities from 2000 to 2023. The current evidence reveals that the NLRP3 inflammasome contributes to the pathogenesis of RA and its comorbidities. Consequently, the components of the NLRP3 inflammasome signaling pathway represent promising therapeutic targets, and ongoing research might lead to the development of new, effective treatments for RA and its comorbidities.

show abstract

AB0007 Shared genetic predisposition in rheumatoid arthritis–interstitial lung disease and familial pulmonary fibrosis

Cited by 11 publications

References 1 publication

Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations

Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations

Serum CHI3L1 as a biomarker of interstitial lung disease in rheumatoid arthritis

The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review

Contact Info

Product

Resources

About