High sensitivity measurement of circulating interferon proteins in systemic lupus erythematosus

Product:

Inflammation Panel 250

Topic:

Inflammation

Disease Area:

Lupus, SLE

Sample Type:

Plasma

Topic/Product:

Inflammation Panel 250

Disease Area:

Lupus, SLE

Sample Type:

Plasma

Abstract

OBJECTIVES:
Increased expression of type I interferon-induced genes is a hallmark of systemic lupus erythematosus (SLE). Measurement of interferon proteins in plasma has been challenging due to their low abundance. Here we utilise a new high sensitivity assay to evaluate levels of interferon proteins in SLE patients.

METHODS:
Seven interferon proteins (type I: IFNα1:IFNα13, IFNα2, IFNβ, IFNω; type II: IFNγ; type III: IFNλ1, IFNλ2:IFNλ3) were measured in 266 SLE patients using the NULISAseq Inflammation Panel 250 (Alamar Biosciences). IFN profiles (normal or high) were determined using the 95th percentile threshold in healthy controls for each IFN protein. Their relationship to disease activity and type I interferon-stimulated gene (ISG) scores was assessed.

RESULTS:
All seven IFN proteins were significantly increased in SLE patients compared to healthy controls and were higher in patients with anti-Sm, anti-Ro and anti-RNP antibodies. IFNα1:IFNα13, IFNα2 and IFNω strongly correlated with the ISG score whereas IFNβ did not. The median levels of IFNα1:IFNα13, IFNα2, IFNω, IFNλ1 and IFNλ2:IFNλ3 progressively increased with disease activity whereas this was not the case for either IFNβ or IFNγ. The most frequent IFN profiles were high type I+III (35%, n=93); normal levels of all IFN proteins (25%, n=67); high type I only (21%, n=56); and high type I+II+III (13%, n=34). The latter associated with serological activity (low complement and high dsDNA antibody titres) and nephritis.

CONCLUSIONS:
Plasma levels of type I IFN proteins (IFNα1: IFNα13, IFNα2 and IFNω but not IFNβ) and type III IFN proteins (IFNλ1, IFNλ2:IFNλ3) were increased in active disease groups and ISG scores recapitulated this. Longitudinal intra-individual measures of these proteins are needed to explore their utility as biomarkers for SLE disease activity.

Authors & Affiliations

Y. Huang¹², C. M. Bottomley¹, R. T. Maughan¹, A. Field¹, G. H. D. Leung¹, L. Lightstone¹³, T. D. Cairns³, T. Turner-Stokes¹³, M. B. Condon³, J. E. Peters¹³, M. Botto¹³, and M. C. Pickering¹³

¹ Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College, London, United Kingdom
² School of Medicine, Chang Gung University, Taoyuan, Taiwan, and Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
³ Imperial Lupus Centre, Imperial College Healthcare NHS Trust, London, United Kingdom

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition. He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.