Brief Report: Anti-Eukaryotic Initiation Factor 2B Autoantibodies Are Associated With Interstitial Lung Disease in Patients With Systemic Sclerosis.
To investigate novel systemic sclerosis (SSc) autoantibodies in autoantibody-negative patients and establish clinical associations.



Serum samples and clinical data for 548 patients with SSc were collected. Routine serologic techniques were used to test the serum samples for known SSc autoantibodies, and samples with negative results were further investigated by radiolabeled-protein immunoprecipitation assay. Sera that immunoprecipitated a novel 30-kd band were analyzed by indirect immunofluorescence and immunoprecipitation, using depleted cell extracts to establish a common reactivity. Mass spectrometry was performed to identify the novel autoantigen, and the results were confirmed using commercial antibodies. Sera from 426 patients with other forms of connective tissue disease, 103 with rheumatoid arthritis, 114 with idiopathic interstitial lung disease (ILD), and 150 healthy subjects were serotyped as controls.



A novel autoantigen with a molecular weight of ∼30 kd was recognized by 7 sera from patients with SSc, 6 of whom had ILD, and by no controls. Six of the patients had diffuse cutaneous involvement, and 4 had overlap features with other autoimmune diseases. Immunodepletion experiments indicated that all samples targeted the same autoantigen, and mass spectrometry identified the novel autoantigen as eukaryotic initiation factor 2B (eIF2B).



We report the identification of a novel autoantibody (anti-eIF2B) in a small number of patients with SSc (∼1%); this autoantibody is closely associated with diffuse cutaneous manifestations and the presence of ILD.
University of Bath, Bath, UK. z.e.betteridge@bath.ac.uk.
Zoe E
ZE
Betteridge
Glenfield Hospital, Leicester, UK.
Felix
F
Woodhead
University of Bath, Bath, UK.
Hui
H
Lu
University of Bath, Bath, UK.
Gavin
G
Shaddick
Royal Free Hospital, London, UK.
Christopher C
CC
Bunn
Royal Free Hospital and University College London Medical School, London, UK.
Christopher P
CP
Denton
University College London, London, UK.
David J
DJ
Abraham
Imperial College London, London, UK.
Roland M
RM
du Bois
University of the West of England, Bristol, UK.
Mervyn
M
Lewis
Royal Brompton Hospital, London, UK.
Athol U
AU
Wells
University of Bath, Bath, UK.
Neil J
NJ
McHugh
D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015153:Blotting, Western; D003378:Counterimmunoelectrophoresis; D004264:DNA Topoisomerases, Type I / Q000276:immunology; D020717:Eukaryotic Initiation Factor-2B / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D047468:Immunoprecipitation; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000276:immunology*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D012320:RNA Polymerase III / Q000276:immunology; D012595:Scleroderma, Systemic / Q000150:complications / Q000276:immunology*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D020717:Eukaryotic Initiation Factor-2B; C538950:anticentromere antibody; D012320:RNA Polymerase III; D004264:DNA Topoisomerases, Type I