Identification of a novel autoantibody directed against small ubiquitin-like modifier activating enzyme in dermatomyositis

Zoe Betteridge, Harsha Gunawardena, Jean North, Jenna Slinn, Neil J McHugh

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Objective
Myositis‐specific autoantibodies (MSAs) are directed against cell machinery proteins such as aminoacyl–transfer RNA synthetases, signal recognition particle, Mi‐2, and CADM‐140. Because serologic subsets can define patients with specific clinical manifestations, the identification of further MSAs may help to identify additional disease subsets within the myositis spectrum.

Methods
Sera from 20 adult patients with dermatomyositis (DM) were screened for autoantibodies. Two patients were further characterized due to the presence of the same novel immunoprecipitation (IP) pattern on sodium docecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE) and similar clinical manifestations. Both patients presented with cutaneous disease, followed by proximal myositis 6 months later. Both patients had associated nonspecific interstitial pneumonia but no signs of malignancy. The novel targets were identified using a combination of IP, SDS‐PAGE, and matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry.

Results
Indirect HEp‐2 immunofluorescence on sera from both patients displayed a diffuse, coarse, speckled, nucleolar‐sparing pattern. IP revealed the presence of previously uncharacterized bands at ∼40 kd and ∼90 kd in both patients. The novel targets were identified as the small ubiquitin‐like modifier 1 (SUMO‐1) activating enzyme A subunit and SUMO‐1 activating enzyme B subunit.

Conclusion
These findings reveal previously uncharacterized autoantibodies directed against a protein involved in posttranslational modification, the SUMO activating enzyme, in 2 patients with DM who had similar clinical features, including severe skin disease and interstitial pneumonia.
Original languageEnglish
Pages (from-to)3132-3137
Number of pages6
JournalArthritis & Rheumatism
Volume56
Issue number9
Early online date30 Aug 2007
DOIs
Publication statusPublished - 1 Sep 2007

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Dermatomyositis
Interstitial Lung Diseases
Post Translational Protein Processing
Ubiquitin
Skin Diseases
Autoantibodies
Enzymes
Proteins

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Identification of a novel autoantibody directed against small ubiquitin-like modifier activating enzyme in dermatomyositis. / Betteridge, Zoe; Gunawardena, Harsha; North, Jean; Slinn, Jenna; McHugh, Neil J.

In: Arthritis & Rheumatism, Vol. 56, No. 9, 01.09.2007, p. 3132-3137.

Research output: Contribution to journalArticle

Betteridge, Zoe ; Gunawardena, Harsha ; North, Jean ; Slinn, Jenna ; McHugh, Neil J. / Identification of a novel autoantibody directed against small ubiquitin-like modifier activating enzyme in dermatomyositis. In: Arthritis & Rheumatism. 2007 ; Vol. 56, No. 9. pp. 3132-3137.
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abstract = "ObjectiveMyositis‐specific autoantibodies (MSAs) are directed against cell machinery proteins such as aminoacyl–transfer RNA synthetases, signal recognition particle, Mi‐2, and CADM‐140. Because serologic subsets can define patients with specific clinical manifestations, the identification of further MSAs may help to identify additional disease subsets within the myositis spectrum.MethodsSera from 20 adult patients with dermatomyositis (DM) were screened for autoantibodies. Two patients were further characterized due to the presence of the same novel immunoprecipitation (IP) pattern on sodium docecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE) and similar clinical manifestations. Both patients presented with cutaneous disease, followed by proximal myositis 6 months later. Both patients had associated nonspecific interstitial pneumonia but no signs of malignancy. The novel targets were identified using a combination of IP, SDS‐PAGE, and matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry.ResultsIndirect HEp‐2 immunofluorescence on sera from both patients displayed a diffuse, coarse, speckled, nucleolar‐sparing pattern. IP revealed the presence of previously uncharacterized bands at ∼40 kd and ∼90 kd in both patients. The novel targets were identified as the small ubiquitin‐like modifier 1 (SUMO‐1) activating enzyme A subunit and SUMO‐1 activating enzyme B subunit.ConclusionThese findings reveal previously uncharacterized autoantibodies directed against a protein involved in posttranslational modification, the SUMO activating enzyme, in 2 patients with DM who had similar clinical features, including severe skin disease and interstitial pneumonia.",
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