anti-eukaryotic initiation factor 2B autoantibodies are associated with interstitial lung disease in patients with systemic sclerosis

Zoe E. Betteridge, Felix Woodhead, Hui Lu, Gavin Shaddick, Christopher C. Bunn, Christopher P. Denton, David J. Abraham, Roland M. du Bois, Mervyn Lewis, Athol U. Wells, Neil J. McHugh

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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.

Original languageEnglish
Pages (from-to)2778-2783
Number of pages6
JournalArthritis & Rheumatology
Volume68
Issue number11
Early online date6 Jun 2016
DOIs
Publication statusPublished - 27 Oct 2016

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Eukaryotic Initiation Factor-2B
Systemic Scleroderma
Interstitial Lung Diseases
Autoantibodies
Autoantigens
Serum
Immunoprecipitation
Mass Spectrometry
Skin Manifestations
Connective Tissue Diseases
Indirect Fluorescent Antibody Technique
Cell Extracts
Autoimmune Diseases
Rheumatoid Arthritis

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anti-eukaryotic initiation factor 2B autoantibodies are associated with interstitial lung disease in patients with systemic sclerosis. / Betteridge, Zoe E.; Woodhead, Felix; Lu, Hui; Shaddick, Gavin; Bunn, Christopher C.; Denton, Christopher P.; Abraham, David J.; du Bois, Roland M.; Lewis, Mervyn; Wells, Athol U.; McHugh, Neil J.

In: Arthritis & Rheumatology, Vol. 68, No. 11, 27.10.2016, p. 2778-2783.

Research output: Contribution to journalArticle

Betteridge, Zoe E. ; Woodhead, Felix ; Lu, Hui ; Shaddick, Gavin ; Bunn, Christopher C. ; Denton, Christopher P. ; Abraham, David J. ; du Bois, Roland M. ; Lewis, Mervyn ; Wells, Athol U. ; McHugh, Neil J. / anti-eukaryotic initiation factor 2B autoantibodies are associated with interstitial lung disease in patients with systemic sclerosis. In: Arthritis & Rheumatology. 2016 ; Vol. 68, No. 11. pp. 2778-2783.
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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.",
author = "Betteridge, {Zoe E.} and Felix Woodhead and Hui Lu and Gavin Shaddick and Bunn, {Christopher C.} and Denton, {Christopher P.} and Abraham, {David J.} and {du Bois}, {Roland M.} and Mervyn Lewis and Wells, {Athol U.} and McHugh, {Neil J.}",
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T1 - anti-eukaryotic initiation factor 2B autoantibodies are associated with interstitial lung disease in patients with systemic sclerosis

AU - Betteridge, Zoe E.

AU - Woodhead, Felix

AU - Lu, Hui

AU - Shaddick, Gavin

AU - Bunn, Christopher C.

AU - Denton, Christopher P.

AU - Abraham, David J.

AU - du Bois, Roland M.

AU - Lewis, Mervyn

AU - Wells, Athol U.

AU - McHugh, Neil J.

N1 - © 2016, American College of Rheumatology.

PY - 2016/10/27

Y1 - 2016/10/27

N2 - 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.

AB - 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.

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