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Anti-Eukaryotic Initiation Factor 2B Autoantibodies are Associated with Interstitial Lung Disease in Patients with Systemic Sclerosis

Betteridge, ZE; Woodhead, F; Lu, H; Shaddick, G; Bunn, CC; Denton, CP; Abraham, DJ; ... McHugh, NJ; + view all (2016) Anti-Eukaryotic Initiation Factor 2B Autoantibodies are Associated with Interstitial Lung Disease in Patients with Systemic Sclerosis. Arthritis & Rheumatology , 68 (11) pp. 2778-2783. 10.1002/art.39755. Green open access

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Abstract

Objective Anti-nuclear autoantibodies are known to occur in 85-99% of Systemic Sclerosis (SSc) patients, with each SSc autoantibody correlating with a distinct clinical subset of patients. The objective of this study was to investigate novel SSc autoantibodies in the remaining autoantibody negative patients and establish clinical associations. Methods Serum samples and clinical data were collected from 548 SSc patients. Sera were tested for known SSc autoantibodies by routine serological techniques, with negative samples being further investigated by radiolabelled protein immunoprecipitation (IPP). Sera that immunoprecipitated a novel 30 kDa band were analysed by indirect immunofluorescence and IPP using depleted cell extracts to establish a common reactivity. Mass spectrometry (MS) was used to identify the novel autoantigen and findings were confirmed using commercial antibodies. Sera from 426 patients with other forms of connective tissue disease, 103 patients with rheumatoid arthritis, 114 patients with idiopathic ILD and 150 healthy controls were serotyped as controls. Results A novel autoantigen with a molecular weight of ∼30 kDa was recognised by seven sera with SSc, six of whom had interstitial lung disease (ILD) and by no controls. Six of the patients had diffuse cutaneous involvement and four had overlap features with other autoimmune diseases. Immunodepletion experiments indicated that all samples targeted the same autoantigen and MS identified the novel autoantigen as eIF2B (Eukaryotic Initiation Factor 2B). Conclusion We report a novel autoantibody (anti-eIF2B) in a small number of patients with SSc (approximately 1%) that is closely associated with diffuse cutaneous manifestations and the presence of ILD. This article is protected by copyright. All rights reserved.

Type: Article
Title: Anti-Eukaryotic Initiation Factor 2B Autoantibodies are Associated with Interstitial Lung Disease in Patients with Systemic Sclerosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/art.39755
Publisher version: http://dx.doi.org/10.1002/art.39755
Language: English
Additional information: Copyright © 2016 American College of Rheumatology. All rights reserved.This is the peer reviewed version of the following article: Betteridge, ZE; Woodhead, F; Lu, H; Shaddick, G; Bunn, CC; Denton, CP; Abraham, DJ; (2016) Anti-Eukaryotic Initiation Factor 2B Autoantibodies are Associated with Interstitial Lung Disease in Patients with Systemic Sclerosis. Arthritis & Rheumatology , 68 (11) pp. 2778-2783, which has been published in final form at 10.1002/art.39755. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1498988
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