scholarly journals High levels of circulating interferons type I, type II and type III associate with distinct clinical features of active systemic lupus erythematosus

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Vilija Oke ◽  
Iva Gunnarsson ◽  
Jessica Dorschner ◽  
Susanna Eketjäll ◽  
Agneta Zickert ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Features ◽  
Lupus Erythematosus ◽  
Active Systemic Lupus Erythematosus ◽  
Type I ◽  
Type Ii ◽  
Systemic Lupus ◽  
Type Iii

Serum concentrations of aminoterminal propeptide of type III procollagen and propeptide of human type I procollagen in systemic lupus erythematosus

2005 ◽  
Vol 26 (8) ◽  
pp. 712-716
Author(s):  
A. I. Villa-Manzano ◽  
J. I. Gamez-Nava ◽  
M. Salazar-Paramo ◽  
I. C. Valera-Gonzalez ◽  
A. Garcia-Gonzalez ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Type I ◽  
Serum Concentrations ◽  
Systemic Lupus ◽  
Type Iii ◽  
Human Type ◽  
Type I Procollagen ◽  
Type Iii Procollagen

scholarly journals Signaling Pathways of Type I and Type III Interferons and Targeted Therapies in Systemic Lupus Erythematosus

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 963 ◽  
Author(s):  
I-Tsu Chyuan ◽  
Hong-Tai Tzeng ◽  
Ji-Yih Chen
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Signaling Pathways ◽  
Lupus Erythematosus ◽  
Janus Kinase ◽  
Type I ◽  
Systemic Lupus ◽  
Type Iii ◽  
Signature Genes

Type I and type III interferons (IFNs) share several properties in common, including the induction of signaling pathways, the activation of gene transcripts, and immune responses, against viral infection. Recent advances in the understanding of the molecular basis of innate and adaptive immunity have led to the re-examination of the role of these IFNs in autoimmune diseases. To date, a variety of IFN-regulated genes, termed IFN signature genes, have been identified. The expressions of these genes significantly increase in systemic lupus erythematosus (SLE), highlighting the role of type I and type III IFNs in the pathogenesis of SLE. In this review, we first discussed the signaling pathways and the immunoregulatory roles of type I and type III IFNs. Next, we discussed the roles of these IFNs in the pathogenesis of autoimmune diseases, including SLE. In SLE, IFN-stimulated genes induced by IFN signaling contribute to a positive feedback loop of autoimmunity, resulting in perpetual autoimmune inflammation. Based on this, we discussed the use of several specific IFN blocking strategies using anti-IFN-α antibodies, anti-IFN-α receptor antibodies, and IFN-α-kinoid or downstream small molecules, which intervene in Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways, in clinical trials for SLE patients. Hopefully, the development of novel regimens targeting IFN signaling pathways will shed light on promising future therapeutic applications for SLE patients.

scholarly journals POS0701 ANIFROLUMAB, AN ANTI-INTERFERON-Α RECEPTOR MONOCLONAL ANTIBODY IN SYSTEMIC LUPUS ERYTHEMATOSUS- A META ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 600.1-600
Author(s):  
A. Abdul Razzack ◽  
S. Abdul Razzack ◽  
P. Shenasan ◽  
N. Shenasan ◽  
S. Mishra ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Monoclonal Antibody ◽  
Adverse Effects ◽  
Lupus Erythematosus ◽  
Active Systemic Lupus Erythematosus ◽  
Interferon Α ◽  
Type I ◽  
Efficacy And Safety ◽  
Systemic Lupus ◽  
Receptor Monoclonal Antibody

Background:Type I interferons such as Anifrolumab have been implicated in Systemic lupus erythematosus (SLE) pathogenesis on the basis of increased interferon-stimulated gene expression and genetic susceptibility. Little is known regarding its efficacy and safety profile.Objectives:To assess the efficacy and safety of Anifrolumab in patients with SLE.Methods:Electronic databases (PubMed, Embase, Scopus, Cochrane) were searched from inception until December 15th, 2020. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p<0.05. The primary outcome of interest was British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). Secondary outcomes included the proportion of patients who achieved an SLE responder index of 4 (SRI-4) reduction of 50% or more in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), reductions in the glucocorticoid dose and adverse effects.Results:A total of three studies1,2,3 with 839 participants (Anifrolumab=372, Placebo=467) were included in our analysis. Follow-up duration was at week 52. A statistically significant different was observed in the Anifrolumab arm in terms of BICLA response (OR 0.44 95%CI 0.34-0.59;p < 0.00001, I2=4), ≥50% reduction in CLASI activity score (OR 0.36 95%CI 0.21-0.60;p=0.0001, I2=0), glucocorticoid reduction (OR 0.41 95%CI 0.28-0.59;p<0.00001; I2=0) and SRI-4 response (OR 0.52 95% CI 0.30-0.90; p=0.02, I2=75). However, Adverse events were less likely in the placebo arm as compared to Anifrolumab (OR 1.54 95%CI 1.05-2.25; p=0.03; I2=0).Conclusion:Anifrolumab was found to be more effective than placebo for the management of SLE, but may also cause more severe adverse effects.References:[1]Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, Bae SC, Brohawn PZ, Pineda L, Berglind A, Tummala R; TULIP-2 Trial Investigators. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020 Jan 16;382(3):211-221. doi: 10.1056/NEJMoa1912196. Epub 2019 Dec 18. PMID: 31851795.[2]Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, Illei GG, Drappa J, Wang L, Yoo S; CD1013 Study Investigators. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017 Feb;69(2):376-386. doi: 10.1002/art.39962. PMID: 28130918; PMCID: PMC5299497.[3]Furie RA, Morand EF, Bruce IN, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol 2019; 1(4):e208-e219.Disclosure of Interests:None declared

scholarly journals Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification

2016 ◽  
Vol 75 (11) ◽  
pp. 2014-2021 ◽  
Author(s):  
Melissa E Munroe ◽  
Rufei Lu ◽  
Yan D Zhao ◽  
Dustin A Fife ◽  
Julie M Robertson ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Random Forest ◽  
Lupus Erythematosus ◽  
Type I Interferon ◽  
Type I ◽  
Type Ii ◽  
Systemic Lupus ◽  
Forest Models ◽  
Random Forest Models ◽  
Α Activity

ObjectivesThe relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type I interferon (IFN-α) activity, and IFN-associated soluble mediators to disease development leading to SLE.MethodsSerial serum specimens from 55 individuals collected prior to SLE classification (average timespan=4.3 years) and unaffected healthy controls matched by age (±5 years), gender, race and time of sample procurement were obtained from the Department of Defense Serum Repository. Levels of serum IFN-α activity, IFN-associated mediators and autoantibodies were evaluated and temporal relationships assessed by growth curve modelling, path analysis, analysis of covariance and random forest models.ResultsIn cases, but not matched controls, autoantibody specificities and IFN-associated mediators accumulated over a period of years, plateauing near the time of disease classification (p<0.001). Autoantibody positivity coincided with or followed type II IFN dysregulation, preceding IFN-α activity in growth curve models, with elevated IFN-α activity and B-lymphocyte stimulator levels occurring shortly before SLE classification (p≤0.005). Cases were distinguished by multivariate random forest models incorporating IFN-γ, macrophage chemoattractant protein (MCP)-3, anti-chromatin and anti-spliceosome antibodies (accuracy 93% >4 years pre-classification; 97% within 2 years of SLE classification).ConclusionsYears before SLE classification, enhancement of the type II IFN pathway allows for accumulation of autoantibodies and subsequent elevations in IFN-α activity immediately preceding SLE classification. Perturbations in select immunological processes may help identify at-risk individuals for further clinical evaluation or participation in prospective intervention trials.

scholarly journals AB0082 PERSISTENT LOW COMPLEMENT LEVELS AND INTERFERON GENE UPREGULATION ARE PREDICTIVE FOR DISEASE PROGRESSION IN PATIENTS WITH INCOMPLETE SYSTEMIC LUPUS ERYTHEMATOSUS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1071.1-1071
Author(s):  
W. Lambers ◽  
J. Westra ◽  
S. Arends ◽  
B. Doornbos- van der Meer ◽  
B. Horvath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Type I Interferon ◽  
Protein A ◽  
Type I ◽  
Type Ii ◽  
Systemic Lupus ◽  
B Cell Activating Factor ◽  
Resistance Protein

Background:A subgroup of lupus patients present with mild symptoms and immunologic features, while they do not meet classification criteria for SLE. This disease state can be referred to as “incomplete systemic lupus erythematosus” (iSLE). Up to 55% of iSLE patients progress to SLE. Furthermore, previous research has shown that iSLE might overlap with early primary Sjögren’s disease (pSS).(1) Unfortunately, there are no predictive markers available for progression to classifiable disease. Type-I interferon (IFN) plays an important role in disease initiation of both SLE and pSS.(2,3) Myxovirus-resistance protein A (MxA) is a GTP-ase that has previously be demonstrated to correlate strongly with IFN-type I expression. Furthermore, interferon-inducible chemokines IFN-γ induced protein 10 (IP-10), and B-cell activating factor (BAFF), that are both inducible by IFN, are of interest, because it is demonstrated that these proteins are increased prior to the diagnosis of SLE.(4)Objectives:To find predictive markers that identify patients with incomplete systemic lupus erythematosus (iSLE) who are at the highest risk to progress to classifiable systemic lupus erythematosus (SLE) or primary Sjögren’s syndrome (pSS).Methods:Patients with iSLE (ANA ≥ 1:80, ≥ 1 clinical SLICC criterion, but not fulfilling the criteria, and disease manifestation <5 years) were included in a longitudinal observational study. Every half year, clinical status was evaluated and regular immunological serologic assessment was performed. Annually, interferon (IFN)-gene expression was determined by RT-PCR in whole blood using 14 genes. These genes represented 3 IFN-related modules. Some genes were mainly inducible by IFN-type I, others by IFN-type II. Furthermore, IFN-related mediators Myxovirus resistance protein A (MxA), interferon-gamma-induced protein 10 (IP-10) and B-cell activating factor (BAFF) were measured.Results:Of 38 included iSLE patients, 6 had developed SLE and 1 develop pSS (18%) after median follow up of 36 months. The 7 patients who developed SLE/pSS were all women, and were younger at baseline than those who remained having iSLE (median 26 years, IQR 20-29 vs. median 42 years, IQR 30-56, p=0.0009). Over time, these patients had significantly lower complement 3 (p<0.0001) and complement 4 levels (p=0.005), higher IFN-gene expression (p=0.007), and lower neutrophil counts (p=0.033) (see Figure 1.). No difference was found between IFN-type I and IFN-type II inducible genes. Levels of MxA, IP-10 and BAFF did not differ between patients who remained iSLE and who progressed to SLE/pSS.Figure 1.Conclusion:Gender, age at diagnosis, persistent low complement levels, and high IFN-gene expression can help to identify iSLE patients at the highest risk of progressing to classifiable disease.References:[1]Md Yusof MY, et al. Prediction of autoimmune connective tissue disease in an at-risk cohort: Prognostic value of a novel two-score system for interferon status. Ann Rheum Dis. 2018;1–8.[2]Yao Y, et al. Type I interferons in Sjögren’s syndrome. Autoimmun Rev. 2013;12(5):558–66.[3]Crow MK. Type I Interferon in the Pathogenesis of Lupus. J Immunol [Internet]. 2014;192(12):5459–68.[4]Lu R, et al. Dysregulation of innate and adaptive serum mediators precedes systemic lupus erythematosus classification and improves prognostic accuracy of autoantibodies. J Autoimmun. 2016;74:182–93.Disclosure of Interests:None declared

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