Interferon signature in systemic autoimmune diseases: what does it mean?

Nocturne, Gaëtane; Mariette, Xavier

doi:10.1136/rmdopen-2022-002687

Cited by 8 publications

(5 citation statements)

References 33 publications

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“…This overlapping effect of the anti-Ro52/TRIM21 antibody on the prognosis of many SADs could be explained by its ability to reflect the level of activation of the IFN pathway, which is frequently dysregulated in patients with these diseases, 39 and this conclusion is in accordance with our observations. Indeed, the unsupervised analysis of the blood transcriptomic data was able to identify the serological status of patients based on DEGs that almost all belonged to the IFN pathway.…”

Section: Discussionsupporting

confidence: 91%

Association of Combined Anti‐Ro52/TRIM21 and Anti‐Ro60/SSA Antibodies With Increased Sjögren Disease Severity Through Interferon Pathway Activation

Bettacchioli,

Saraux,

Tison

et al. 2024

Arthritis & Rheumatology

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ObjectiveThe biological diagnosis of primary Sjögren's disease (SjD) mainly relies on anti‐Ro60/SSA antibodies, while the significance of anti‐Ro52/TRIM21 antibodies currently remains unclear. The aim of this study was to characterize the clinical, serological, biological, transcriptomic and interferon profiles of SjD patients according to their anti‐Ro52/TRIM21 antibody status.MethodsSjD patients from the European PRECISESADS (n=376) and the Brittany DIApSS (n=146) cohorts were divided into four groups: double negative (Ro52‐/Ro60‐), isolated anti‐Ro52/TRIM21 positive (Ro52+), isolated anti‐Ro60/SSA positive (Ro60+), and double positive (Ro52+/Ro60+) patients. Clinical information, ESSDAI, a score representing systemic activity, and biological markers associated with disease severity were evaluated. Transcriptome data obtained from whole blood by RNAseq and type I and type II interferon signatures were analysed for PRECISESADS patients.ResultsIn the DIAPSS cohort, Ro52+/Ro60+ patients showed significantly more parotidomegaly (33.3% vs 0‐11%), along with higher β2‐microglobulin (p=0.0002), total immunoglobulin (p<0.0001), erythrocyte sedimentation rate levels (p=0.002), and rheumatoid factor (RF) positivity (66.2% vs. 20.8%‐25%) compared to other groups. The PRECISESADS cohort corroborated these observations, with increased arthritis (p=0.046), inflammation (p=0.005), hypergammaglobulinemia (p<0.0001), positive RF (p<0.0001), leukopenia (p=0.004), and lymphopenia (p=0.009) in Ro52+/Ro60+ patients. Cumulative ESSDAI results further confirmed these disparities (p=0.002). Transcriptome analysis linked anti‐Ro52/TRIM21 antibody positivity to interferon pathway activation, as an underlying cause for these clinical correlations.ConclusionThese results suggest that the combination of anti‐Ro52/TRIM21 and anti‐Ro60/SSA antibodies is associated with a clinical, biological, and transcriptional profile linked to greater disease severity in SjD, through the potentiation of the interferon pathway activation by anti‐Ro52/TRIM21 antibodies.image

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Section: Discussionsupporting

confidence: 91%

Association of Combined Anti‐Ro52/TRIM21 and Anti‐Ro60/SSA Antibodies With Increased Sjögren Disease Severity Through Interferon Pathway Activation

Bettacchioli,

Saraux,

Tison

et al. 2024

Arthritis & Rheumatology

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“…The application of multiplex RT-qPCR in this study of IFN-I scores in patients with anti-MDA5+ DM was innovative. The limitation of not being able to differentiate between the two IFN families was overcome by this approach, which covers both type I and type II IFN-stimulated genes, whereas previous gene sets only allowed differentiation into high and low IFN scores (24). As anticipated, the IFN-I score was increased in more than 80% of patients with anti-MDA5+ DM and was significantly higher in individuals with anti-MDA5+ DM than in patients with SLE, RA, AOSD, and SS.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple markers are associated with the prognosis of anti-MDA5+ DM, including anti-MDA5 titers (41,42), the presence of anti-Ro52 antibody (43), lactate dehydrogenase (18), ferritin (5,24,26), KL-6 (27), the proportion of CD4+ CXCR4+ T cells (28), and a high proportion of ISG15+ CD8+ T cells (16). The presence of interstitial lung disease, particularly rapidly progressive interstitial lung disease, poses significant obstacles to the prognosis of patients with anti-MDA5+ DM.…”

Section: Discussionmentioning

confidence: 99%

Type I interferon score is associated with the severity and poor prognosis in anti-MDA5 antibody-positive dermatomyositis patients

Qian

Chen

et al. 2023

Front. Immunol.

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ObjectivesTo investigate the clinical significance of the interferon (IFN) score, especially the IFN-I score, in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (anti-MDA5+ DM).MethodsWe enrolled 262 patients with different autoimmune diseases, including idiopathic inflammatory myopathy, systemic lupus erythematosus, rheumatoid arthritis, adult-onset Still’s disease, and Sjögren’s syndrome, as well as 58 healthy controls. Multiplex quantitative real-time polymerase chain reaction (RT-qPCR) using four TaqMan probes was used to evaluate type I IFN-stimulated genes (IFI44 and MX1), one type II IFN-stimulated gene (IRF1), and one internal control gene (HRPT1), which were used to determine the IFN-I score. The clinical features and disease activity index were compared between the high and low IFN-I score groups in 61 patients with anti-MDA5+ DM. The associations between laboratory findings and the predictive value of the baseline IFN-I score for mortality were analyzed.ResultsThe IFN score was significantly higher in patients with anti-MDA5+ DM than in healthy controls. The IFN-I score was positively correlated with the serum IFN-α concentration, ferritin concentration, and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) score. Compared with patients with a low IFN-I score, patients with a high IFN-I score showed a higher MYOACT score, C-reactive protein concentration, aspartate transaminase concentration, ferritin concentration, plasma cell percentage, and CD3+ T-cell percentage, as well as lower lymphocyte, natural killer cell, and monocyte counts. The 3-month survival rate was significantly lower in patients with an IFN-I score of >4.9 than in those with an IFN-I score of ≤4.9 (72.9% vs. 100%, respectively; P = 0.044).ConclusionThe IFN score, especially the IFN-I score, measured by multiplex RT-qPCR is a valuable tool to monitor disease activity and predict mortality in patients with anti-MDA5+ DM.

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“…Numerous studies have validated the involvement of interferons in the pathogenesis of SSc [21,48,49]. Furthermore, a substantial body of evidence has established interferons as highly pleiotropic cytokines that play a pathogenetic role in diseases such as systemic lupus erythematosus, rheumatoid arthritis, idiopathic inflammatory myositis, and systemic sclerosis [50][51][52][53][54][55]. The activity of interferons is precisely regulated by interferon regulatory factors (IRFs).…”

Section: The Interferon Regulatory Factor Genesmentioning

confidence: 99%

Immunogenetics of Systemic Sclerosis

Gumkowska-Sroka,

Kotyla,

Kotyla

2024

Genes

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Systemic sclerosis (SSc) is a rare autoimmune connective tissue disorder characterized by massive fibrosis, vascular damage, and immune imbalance. Advances in rheumatology and immunology over the past two decades have led to a redefinition of systemic sclerosis, shifting from its initial perception as primarily a “hyperfibrotic” state towards a recognition of systemic sclerosis as an immune-mediated disease. Consequently, the search for genetic markers has transitioned from focusing on fibrotic mechanisms to exploring immune regulatory pathways. Immunogenetics, an emerging field at the intersection of immunology, molecular biology, and genetics has provided valuable insights into inherited factors that influence immunity. Data from genetic studies conducted thus far indicate that alterations in genetic messages can significantly impact disease risk and progression. While certain genetic variations may confer protective effects, others may exacerbate disease susceptibility. This paper presents a comprehensive review of the most relevant genetic changes that influence both the risk and course of systemic sclerosis. Special emphasis is placed on factors regulating the immune response, recognizing their pivotal role in the pathogenesis of the disease.

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Interferon signature in systemic autoimmune diseases: what does it mean?

Cited by 8 publications

References 33 publications

Association of Combined Anti‐Ro52/TRIM21 and Anti‐Ro60/SSA Antibodies With Increased Sjögren Disease Severity Through Interferon Pathway Activation

Association of Combined Anti‐Ro52/TRIM21 and Anti‐Ro60/SSA Antibodies With Increased Sjögren Disease Severity Through Interferon Pathway Activation

Type I interferon score is associated with the severity and poor prognosis in anti-MDA5 antibody-positive dermatomyositis patients

Immunogenetics of Systemic Sclerosis

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