Autoinflammatory manifestations in adult patients

Rodolfi, Stefano; Nasone, Irene; Folci, Marco; Selmi, Carlo; Brunetta, Enrico

doi:10.1093/cei/uxac098

Cited by 4 publications

(2 citation statements)

References 129 publications

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“…The genetics and biology of myocarditis are not well understood; our findings create novel understanding on biological mechanisms associated with myocarditis and cardiovascular manifestations of autoinflammatory conditions [13,27]. Our experience may also bring understanding on myocarditis caused by immune checkpoint inhibitor treatments [24].…”

Section: Il-1β Inf-γ and Stat Responsesmentioning

confidence: 88%

Germline HAVCR2/TIM-3 Checkpoint Inhibitor Receptor Deficiency in Recurrent Autoinflammatory Myocarditis

Pernaa,

Vakkuri,

Arvonen

et al. 2024

J Clin Immunol

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Myocarditis can be caused by viral infection, drug reaction or general inflammatory condition. To provide understanding on inflammatory myocarditis, we describe clinical, genetic, and immunological properties of a young male patient who suffered from recurrent myocarditis episodes since the age of four years. Electrocardiography, troponin I/T, echocardiography, myocardial magnetic resonance imaging and histological findings were consistent with recurrent myocarditis episodes. Homozygous c.245 A > G p.Tyr82Cys pathogenic variant in Hepatitis A Virus Cellular Receptor 2 (HAVCR2) gene encoding T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) receptor was found. Peripheral blood mononuclear cells were collected when the patient was asymptomatic; CD4+ and CD8+ T lymphoblasts, CD56+ natural killer cells and CD14+ monocytes were negative for surface TIM-3 expression. In vitro, TLR4 mediated interleukin-1β (IL-1β) response was high after LPS/ATP stimulation. Clinical symptoms responded to IL-1 receptor antagonist anakinra. TIM-3 p.Tyr82Cys CD4+ and CD8+ T cell proliferation in vitro was unrestrained. Findings on IL-2, interferon gamma, regulatory T cells, signal transducer and activator of transcription (STAT) 1, 3 and 4 phosphorylation, and PD-1 and LAG-3 checkpoint inhibitor receptor analyses were comparable to controls. We conclude that TIM-3 deficiency due to homozygous HAVCR2 c.245 A > G p.Tyr82Cys pathogenic variant in the patient described here is associated with autoinflammatory symptoms limited to early onset recurrent febrile myocarditis. Excessive IL-1β production and defective regulation of T cell proliferation may contribute to this clinical condition responsive to anakinra treatment.

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Section: Il-1β Inf-γ and Stat Responsesmentioning

confidence: 88%

Germline HAVCR2/TIM-3 Checkpoint Inhibitor Receptor Deficiency in Recurrent Autoinflammatory Myocarditis

Pernaa,

Vakkuri,

Arvonen

et al. 2024

J Clin Immunol

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“…Behçet’s disease (BD) is a chronic autoimmune disorder characterized by widespread vasculitis that can affect any bodily system 1 . While the prognosis for most BD patients is favorable, cardiovascular involvement significantly worsens the outlook.…”

Section: Introductionmentioning

confidence: 99%

Exploration of effective biomarkers for venous thrombosis embolism in Behçet’s disease based on comprehensive bioinformatics analysis

Liu,

Wang,

et al. 2024

Sci Rep

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Behçet’s disease (BD) is a multifaceted autoimmune disorder affecting multiple organ systems. Vascular complications, such as venous thromboembolism (VTE), are highly prevalent, affecting around 50% of individuals diagnosed with BD. This study aimed to identify potential biomarkers for VTE in BD patients. Three microarray datasets (GSE209567, GSE48000, GSE19151) were retrieved for analysis. Differentially expressed genes (DEGs) associated with VTE in BD were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). Subsequently, potential diagnostic genes were explored through protein–protein interaction (PPI) network analysis and machine learning algorithms. A receiver operating characteristic (ROC) curve and a nomogram were constructed to evaluate the diagnostic performance for VTE in BD patients. Furthermore, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate potential underlying mechanisms. Finally, the efficacy of listed drugs was assessed based on the identified signature genes. The limma package and WGCNA identified 117 DEGs related to VTE in BD. A PPI network analysis then selected 23 candidate hub genes. Four DEGs (E2F1, GATA3, HDAC5, and MSH2) were identified by intersecting gene sets from three machine learning algorithms. ROC analysis and nomogram construction demonstrated high diagnostic accuracy for these four genes (AUC: 0.816, 95% CI: 0.723–0.909). Immune cell infiltration analysis revealed a positive correlation between dysregulated immune cells and the four hub genes. ssGSEA provided insights into potential mechanisms underlying VTE development and progression in BD patients. Additionally, therapeutic agent screening identified potential drugs targeting the four hub genes. This study employed a systematic approach to identify four potential hub genes (E2F1, GATA3, HDAC5, and MSH2) and construct a nomogram for VTE diagnosis in BD. Immune cell infiltration analysis revealed dysregulation, suggesting potential macrophage involvement in VTE development. ssGSEA provided insights into potential mechanisms underlying BD-induced VTE, and potential therapeutic agents were identified.

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NF-κB and Related Autoimmune and Autoinflammatory Diseases

Freigeh,

Michniacki

2023

Rheumatic Disease Clinics of North America

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Autoinflammatory manifestations in adult patients

Cited by 4 publications

References 129 publications

Germline HAVCR2/TIM-3 Checkpoint Inhibitor Receptor Deficiency in Recurrent Autoinflammatory Myocarditis

Germline HAVCR2/TIM-3 Checkpoint Inhibitor Receptor Deficiency in Recurrent Autoinflammatory Myocarditis

Exploration of effective biomarkers for venous thrombosis embolism in Behçet’s disease based on comprehensive bioinformatics analysis

NF-κB and Related Autoimmune and Autoinflammatory Diseases

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