title: Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis.
abstract: Type I IFNs are implicated in the pathophysiology of systemic sclerosis (SSc). Recently, a Phase I open-label trial was conducted with an anti-IFNAR1 receptor antibody (anifrolumab) in adult SSc patients. In this study, we aim to assess the downstream effects of anifrolumab and elucidate the role of type I IFN in SSc. Serum proteins and extracellular matrix (ECM) markers were measured in relation to IFN pathway activation status and SSc disease activity. Our results demonstrated a robust overexpression of multiple serum proteins in SSc patients, particularly those with an elevated baseline type I IFN gene signature. Anifrolumab administration was associated with significant downregulation of T cell-associated proteins and upregulation of type III collagen degradation marker. Whole-blood and skin microarray results also indicated the inhibition of T cell receptor and ECM-related transcripts by anifrolumab. In summary, our study demonstrates suppressive effects of anifrolumab on T cell activation and collagen accumulation through which tissue fibrosis may be reduced in SSc patients. The relationship between these peripheral markers and the clinical response to anifrolumab may be examined in larger double-blind, placebo-controlled trials.
authors.affiliation: Translational Sciences, MedImmune LLC, Gaithersburg, Maryland, USA. Electronic address: guox@medimmune.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Translational Sciences, MedImmune LLC, Gaithersburg, Maryland, USA.
authors.forename: Brandon W
authors.initials: BW
authors.lastname: Higgs
authors.affiliation: Nordic Bioscience, Herlev, Denmark.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Bay-Jensen
authors.affiliation: Nordic Bioscience, Herlev, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Translational Sciences, MedImmune LLC, Gaithersburg, Maryland, USA.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Translational Sciences, MedImmune LLC, Gaithersburg, Maryland, USA.
authors.forename: Lorin K
authors.initials: LK
authors.lastname: Roskos
authors.affiliation: Translational Sciences, MedImmune LLC, Gaithersburg, Maryland, USA.
authors.forename: Wendy I
authors.initials: WI
authors.lastname: White
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D024042:Collagen Type I / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D061214:Patient Safety; D053633:Receptor, Interferon alpha-beta / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D018570:Risk Assessment; D012595:Scleroderma, Systemic / Q000097:blood* / Q000188:drug therapy*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D024042:Collagen Type I; C507964:IFNAR1 protein, human; D053633:Receptor, Interferon alpha-beta; C582345:anifrolumab