IMMUNOINFLAMMATORY RHEUMATIC DISEASES ASSOCIATED WITH TYPE I INTERFERON: NEW EVIDENCE

2019 ◽  
Vol 57 (4) ◽  
pp. 452-461 ◽  
Author(s):  
E. L. Nasonov ◽  
A. S. Avdeeva
Keyword(s):  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Type I Interferon ◽  
Organ Damage ◽  
Immunological Tolerance ◽  
Type I Interferons ◽  
Type I ◽  
Pathological Conditions ◽  
New Evidence

Immunoinflammatory rheumatic diseases (IIRDs) are a large group of pathological conditions with impaired immunological tolerance to autogenous tissues, leading to inflammation and irreversible organ damage. The review discusses current ideas on the role of type I interferons in the immunopathogenesis of IIRDs, primarily systemic lupus erythematosus, and new possibilities for personalized therapy.

Type I Interferons in Autoimmune Disease

2019 ◽  
Vol 14 (1) ◽  
pp. 369-393 ◽  
Author(s):  
Mary K. Crow ◽  
Mikhail Olferiev ◽  
Kyriakos A. Kirou
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Type I Interferon ◽  
Type I Interferons ◽  
Type I ◽  
Systemic Lupus ◽  
Pathway Activation ◽  
Interferon Pathway ◽  
Chronic Activation

Type I interferons, which make up the first cytokine family to be described and are the essential mediators of antivirus host defense, have emerged as central elements in the immunopathology of systemic autoimmune diseases, with systemic lupus erythematosus as the prototype. Lessons from investigation of interferon regulation following virus infection can be applied to lupus, with the conclusion that sustained production of type I interferon shifts nearly all components of the immune system toward pathologic functions that result in tissue damage and disease. We review recent data, mainly from studies of patients with systemic lupus erythematosus, that provide new insights into the mechanisms of induction and the immunologic consequences of chronic activation of the type I interferon pathway. Current concepts implicate endogenous nucleic acids, driving both cytosolic sensors and endosomal Toll-like receptors, in interferon pathway activation and suggest targets for development of novel therapeutics that may restore the immune system to health.

scholarly journals Mechanisms of type I interferon action and its role in infections and diseases transmission in mammals

2017 ◽  
Vol 64 (2) ◽  
Author(s):  
Weronika Ratajczak ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Beata Tokarz-Deptuła ◽  
Wiesław Deptuła
Keyword(s):  
Signaling Pathways ◽  
Crucial Role ◽  
Viral Infections ◽  
Type I Interferon ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Stimulated Genes

Interferons (IFN) are pivotal regulators of immunological processes. The paper describes mainly type I interferons -α and –β and its recently recounted signaling pathways, especially ISG – interferon stimulated genes, having a crucial role in regulating IFN recruitment. Moreover, the paper shows the data on the role of interferons -α and –β in infections – not only commonly known viral infections, but also bacterial, fungal and parasitic. 

scholarly journals Resolution of the Expert Council «The role of type I interferon inhibitor in the treatment of patients with systemic lupus erythematosus»

2021 ◽  
Vol 15 (4) ◽  
pp. 126-128
Author(s):  
A. M. Lila ◽  
S. K. Soloviev ◽  
T. V. Popkova
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Organ Damage ◽  
Immunosuppressive Drugs ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
Key Points

On April 28, 2021, a meeting of the Council of Experts was held with the participation of the leading experts in the field of rheumatic diseases, approaches to the treatment of patients with systemic lupus erythematosus (SLE) were discussed. The issues of medical care for patients with SLE and their routing, key points of Russian and international clinical guidelines for the management of patients with SLE, as well as the role of interferon (IFN) type I in the pathogenesis of the disease were discussed. It is noted that the management of patients with SLE requires a multidisciplinary approach. The basis of therapy is the use of glucocorticoids (GC), immunosuppressive drugs and their combinations. But long-term use of GC in patients with SLE leads to severe complications. Early prescription of biological disease-modifying antirheumatic drugs (bDMARDs) allows to achieve the greatest effect and prevent the development of irreversible organ damage associated with SLE. Currently data from three clinical trials on the efficacy and safety of the type I IFN inhibitor anifrolumab are available. During the discussion, experts defined the clinical profile of a patient with SLE, for whom administration of bDMARD therapy is indicated. According to experts, the use of a type I IFN inhibitor in routine clinical practice can improve disease outcomes in both short and long term.

scholarly journals Levels of type I interferon in patients with systemic lupus erythematosus

2021 ◽  
pp. 16-20
Author(s):  
C. Erramuspe ◽  
M. Racca ◽  
M. Siemsen ◽  
M. Pelosso ◽  
M. Quaglia ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Type I Interferon ◽  
Organ Damage ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
Dsdna Antibodies ◽  
Different Levels

Introduction: type I interferon (IFN) is a cytokine that plays a fundamental role in the pathogenesis of Systemic Lupus Erythematosus (SLE). Different levels of this cytokine could explain the heterogeneity of this pathology and be useful to evaluate its activity. Objectives: to determine the serum type I IFN levels in patients with SLE and evaluate its usefulness as a biomarker of activity. Material and Method: 16 patients with SLE (ACR 1997) and 16 controls. Methods: Disease activity (SLEDAI-2K), organ damage (SLICC), type I IFN (HEK-Blue- IFNα/β), anti-dsDNA antibodies (Indirect Immunofluorescence), anti-ENA antibodies (ELISA), C3-C4 (Immunoturbidimetry). Statistics: InfoStat/Instat/MedCalc. P values <0.05 were statistically significant. Results: an increase in IFN concentration was observed in the SLE group respect to the control (p <0.05). Patients with IFN values above the cut-off point were associated with the presence of anti-dsDNA antibodies (OR: 13.33; p<0.05). Hypocomplementemic patients and those with a SLEDAI-2K score greater than 8 had higher IFN levels compared to patients with normal complement and a lower index score, respectively (p<0.05). Conclusions: these results suggest the importance that the determination of IFN type I could have for the monitoring of SLE activity.

scholarly journals The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Isaac T. W. Harley ◽  
Timothy B. Niewold ◽  
Rebecca M. Stormont ◽  
Kenneth M. Kaufman ◽  
Stuart B. Glenn ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Type I Interferons ◽  
Systemic Autoimmune Disease ◽  
Type I ◽  
Nucleotide Polymorphisms ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
Genome Wide

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased type I interferons (IFNs) and multiorgan inflammation frequently targeting the skin. IFN-kappa is a type I IFN expressed in skin. A pooled genome-wide scan implicated theIFNKlocus in SLE susceptibility. We studiedIFNKsingle nucleotide polymorphisms (SNPs) in 3982 SLE cases and 4275 controls, composed of European (EA), African-American (AA), and Asian ancestry. rs12553951C was associated with SLE in EA males (odds ratio=1.93,P=2.5×10−4), but not females. Suggestive associations with skin phenotypes in EA and AA females were found, and these were also sex-specific.IFNKSNPs were associated with increased serum type I IFN in EA and AA SLE patients. Our data suggest a sex-dependent association betweenIFNKSNPs and SLE and skin phenotypes. The serum IFN association suggests thatIFNKvariants could influence type I IFN producing plasmacytoid dendritic cells in affected skin.

Distinct Roles of Type I and Type III Interferons During a Native Murine β Coronavirus Lung Infection

2021 ◽  
Author(s):  
Lokesh Sharma ◽  
Xiaohua Peng ◽  
Hua Qing ◽  
Brandon K. Hilliard ◽  
Jooyoung Kim ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Lung Infection ◽  
Viral Clearance ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Signaling ◽  
Type Iii ◽  
Coronavirus Infection ◽  
Type Iii Interferon

Coronaviruses are a major healthcare threat to humankind. Currently, the host factors that contribute to limit disease severity in healthy young patients are not well defined. Interferons are key antiviral molecules, especially type I and type III interferons. The role of these interferons during coronavirus disease is a subject of debate. Here using mice that are deficient in type I (IFNAR1 -/- ), type III (IFNLR1 -/- ) or both (IFNAR1/LR1 -/- ) interferon signaling pathways and murine adapted coronavirus (MHV-A59) administered through intranasal route, we define the role of interferons in coronavirus infection. We show that type I interferons play a major role in host survival in this model while a minimal role of type III interferons was manifested only in the absence of type I interferons or during a lethal dose of coronavirus. IFNAR1 -/- and IFNAR1/LR1 -/- mice had an uncontrolled viral burden in the airways and lung and increased viral dissemination to other organs. The absence of only type III interferon signaling had no measurable difference in the viral load. The increased viral load in IFNAR1 -/- and IFNAR1/LR1 -/- mice was associated with increased tissue injury, especially evident in the lung and liver. Type I but not type III interferon treatment was able to promote survival if treated during early disease. Further, we show that type I interferon signaling in macrophages contributes to the beneficial effects during coronavirus infection in mice. Importance: The antiviral and pathological potential of type I and type III interferons during coronavirus infection remains poorly defined and opposite findings have been reported. We report that both type I and type III interferons have anti-coronaviral activities, but their potency and organ specificity differ. Type I interferons deficiency rendered the mice susceptible to even a sublethal murine coronavirus infection, while the type III interferon deficiency impaired survival only during a lethal infection or during a sublethal infection in absence of type I interferon signaling. While treatment with both type I and III interferons promoted viral clearance in the airways and lung, only type I interferons promoted the viral clearance in the liver and improved host survival upon early treatment (12 hours post infection). This study demonstrates distinct roles and potency of type I and type III interferons and their therapeutic potential during coronavirus lung infection.

scholarly journals Activation of Type I Interferon Pathway in Systemic Lupus Erythematosus: Association with Distinct Clinical Phenotypes

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Theophanis P. Karageorgas ◽  
Dimitrios D. Tseronis ◽  
Clio P. Mavragani
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Type I Interferon ◽  
Clinical Manifestations ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
Genetic Studies ◽  
Interferon Pathway

Growing evidence over the last few years suggests a central role of type I IFN pathway in the pathogenesis of systemic autoimmune disorders. Data from clinical and genetic studies in patients with systemic lupus erythematosus (SLE) and lupus-prone mouse models, indicates that the type I interferon system may play a pivotal role in the pathogenesis of several lupus and associated clinical features, such as nephritis, neuropsychiatric and cutaneous lupus, premature atherosclerosis as well as lupus-specific autoantibodies particularly against ribonucleoproteins. In the current paper, our aim is to summarize the latest findings supporting the association of type I IFN pathway with specific clinical manifestations in the setting of SLE providing insights on the potential use of type I IFN as a therapeutic target.

scholarly journals Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus

2021 ◽  
Vol 22 (21) ◽  
pp. 11747
Author(s):  
Tom Aschman ◽  
Sandra Schaffer ◽  
Stylianos Iason Biniaris Georgallis ◽  
Antigoni Triantafyllopoulou ◽  
Peter Staeheli ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Survival Rates ◽  
Mononuclear Phagocytes ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Signaling ◽  
Type Iii ◽  
Cellular And Humoral Immunity ◽  
Type Iii Interferon

A pivotal role of type I interferons in systemic lupus erythematosus (SLE) is widely accepted. Type III interferons (IFN-λ) however, the most recently discovered cytokines grouped within the interferon family, have not been extensively studied in lupus disease models yet. Growing evidence suggests a role for IFN-λ in regulating both innate and adaptive immune responses, and increased serum concentrations have been described in multiple autoimmune diseases including SLE. Using the pristane-induced lupus model, we found that mice with defective IFN-λ receptors (Ifnlr1−/−) showed increased survival rates, decreased lipogranuloma formation and reduced anti-dsDNA autoantibody titers in the early phase of autoimmunity development compared to pristane-treated wild-type mice. Moreover, Ifnlr1−/− mice treated with pristane had reduced numbers of inflammatory mononuclear phagocytes and cNK cells in their kidneys, resembling untreated control mice. Systemically, circulating B cells and monocytes (CD115+Ly6C+) were reduced in pristane-treated Ifnlr1−/− mice. The present study supports a significant role for type III interferons in the pathogenesis of pristane-induced murine autoimmunity as well as in systemic and renal inflammation. Although the absence of type III interferon receptors does not completely prevent the development of autoantibodies, type III interferon signaling accelerates the development of autoimmunity and promotes a pro-inflammatory environment in autoimmune-prone hosts.

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