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Arthritis Rheumatol. 2019 Jul 24. doi: 10.1002/art.41054. [Epub ahead of print]

High prevalence and disease correlation of autoantibodies against p40 encoded by long interspersed nuclear elements (LINE-1) in systemic lupus erythematosus.

Author information

1
Division of Rheumatology, Department of Medicine, University of Washington, 750 Republican Street, Room E507, Seattle, WA, 99108.
2
Laboratory of Cellular and Structural Biology, The Rockefeller University, 1230 York Avenue, New York, NY, 10065.
3
European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, The Netherlands.
4
Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114.
5
Whitehead Institute, 455 Main Street, Cambridge, MA, 02142.
6
Department of Rheumatology, Lund University, Lund, Sweden.

Abstract

OBJECTIVE:

The long interspersed nuclear element 1 (LINE-1) encodes two proteins, the RNA-binding p40 and the endonuclease and reverse transcriptase (ORF2p); both required for LINE-1 to retrotranspose. In cells expressing LINE-1, these proteins assemble with the LINE-1 RNA and additional RNA-binding proteins, some of which are well-known autoantigens in patients with systemic lupus erythematosus (SLE). We asked if SLE patients also make autoantibodies against the LINE-1 p40.

METHODS:

Highly purified p40 protein was used to quantitate IgG autoantibodies in the serum of 172 SLE patients, disease controls, and age-matched healthy subjects by immunoblotting and ELISA. Preparations of p40 that also contained associated proteins were analyzed by immunoblotting with patient sera.

RESULTS:

Antibodies reactive with p40 were detected in the majority of patients and many healthy controls: they were higher in patients with SLE, but not systemic sclerosis, compared to healthy subjects (p=0.01). The anti-p40 reactivity was higher in patients during a flare than in remission (p=0.03), correlated with SLEDAI (p=0.0002), type I interferon score (p=0.006), complement C3 decrease (p=0.0001), anti-DNA antibodies (p<0.0001), anti-C1q antibodies (p=0.004), current or past history of nephritis (p=0.02 and 0.003), and they correlated inversely with age (r=-0.49, p<0.0001). SLE patient sera also reacted with p40-associated proteins.

CONCLUSIONS:

Autoantibodies reacting with LINE-1 p40 characterize a population of SLE patients with severe and active disease. These autoantibodies may represent an early immune response against LINE-1 p40 that does not yet by itself imply clinically significant autoimmunity, but may represent an early, and still reversible, step towards SLE pathogenesis. This article is protected by copyright. All rights reserved.

PMID:
31342656
DOI:
10.1002/art.41054

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