Physiological evidence for diversification of IFNα- and IFNβ-mediated response programs in different autoimmune diseases.

Autor: de Jong TD; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. td.dejong@vumc.nl., Vosslamber S; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. s.vosslamber@vumc.nl., Mantel E; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. e.mantel@vumc.nl., de Ridder S; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. s.deridder@vumc.nl., Wesseling JG; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. j.g.wesseling@durrercenter.nl., van der Pouw Kraan TC; Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. t.vanderpouwkraan@vumc.nl., Leurs C; Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. c.leurs@vumc.nl., Hegen H; Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. harald.hegen@i-med.ac.at., Deisenhammer F; Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Florian.Deisenhammer@tirol-kliniken.at., Killestein J; Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. j.killestein@vumc.nl., Lundberg IE; Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden. Ingrid.Lundberg@ki.se., Vencovsky J; Institute of Rheumatology, Prague, Czech Republic. vencovsky@revma.cz., Nurmohamed MT; Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands. m.nurmohamed@reade.nl., van Schaardenburg D; Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands. d.v.schaardenburg@reade.nl., Bultink IE; Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, VUmc, Amsterdam, The Netherlands. IEM.Bultink@vumc.nl., Voskuyl AE; Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, VUmc, Amsterdam, The Netherlands. AE.Voskuyl@vumc.nl., Pegtel DM; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. d.pegtel@vumc.nl., van der Laken CJ; Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, VUmc, Amsterdam, The Netherlands. J.vanderLaken@vumc.nl., Bijlsma JW; Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands. j.bijlsma@vumc.nl.; Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, VUmc, Amsterdam, The Netherlands. j.bijlsma@vumc.nl., Verweij CL; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. c.verweij@vumc.nl.; Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, VUmc, Amsterdam, The Netherlands. c.verweij@vumc.nl.
Jazyk: angličtina
Zdroj: Arthritis research & therapy [Arthritis Res Ther] 2016 Feb 17; Vol. 18, pp. 49. Date of Electronic Publication: 2016 Feb 17.
DOI: 10.1186/s13075-016-0946-9
Abstrakt: Background: Activation of the type I interferon (IFN) response program is described for several autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS), myositis (IIM) and rheumatoid arthritis (RA). While IFNα contributes to SLE pathology, IFNβ therapy is often beneficial in MS, implying different immunoregulatory roles for these IFNs. This study was aimed to investigate potential diversification of IFNα-and IFNβ-mediated response programs in autoimmune diseases.
Methods: Peripheral blood gene expression of 23 prototypical type I IFN response genes (IRGs) was determined in 54 healthy controls (HCs), 69 SLE (47 test, 22 validation), 149 IFNβ-treated MS (71 test, 78 validation), 160 untreated MS, 78 IIM and 76 RA patients. Patients with a type I IFN signature were selected for analysis.
Results: We identified IFNα- and IFNβ-specific response programs (GC-A and GC-B, respectively) in SLE and IFNβ-treated MS patients. Concordantly, the GC-A/GC-B log-ratio was positive for all SLE patients and negative for virtually all IFNβ-treated MS patients, which was confirmed in additional cohorts. Applying this information to other autoimmune diseases, IIM patients displayed positive GC-A/GC-B log-ratios, indicating predominant IFNα activity. The GC-A/GC-B log-ratio in RA was lower and approached zero in part of the patients, implying relative importance of both clusters. Remarkably, GC-A/GC-B log-ratios appeared most heterogeneous in untreated MS; half of the patients displayed GC-A dominance, whereas others showed GC-B dominance or log-ratios near zero.
Conclusions: Our findings show diversification of the type I IFN response in autoimmune diseases, suggesting different pathogenic roles of the type I IFNs.
Databáze: MEDLINE
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