High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus
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Objective: Long interspersed nuclear element 1 (LINE‐1) encodes 2 proteins, the RNA binding protein p40 and endonuclease and reverse transcriptase (open‐reading frame 2p [ORF 2p]), which are both required for LINE‐1 to retrotranspose. In cells expressing LINE‐1, these proteins assemble with LINE‐1 RNA and additional RNA binding proteins, some of which are well‐known autoantigens in patients with systemic lupus erythematosus (SLE). This study was undertaken to investigate whether SLE patients also produce autoantibodies against LINE‐1 p40. Methods: Highly purified p40 protein was used to quantitate IgG autoantibodies in serum from 172 SLE patients and from disease controls and age‐matched healthy subjects by immunoblotting and enzyme‐linked immunosorbent assay (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. Their levels were higher in patients with SLE, but not those with systemic sclerosis, compared to healthy subjects (P = 0.01). Anti‐p40 reactivity was higher in patients during a flare than in patients with disease in remission (P = 0.03); correlated with the SLE Disease Activity Index score (P = 0.0002), type I interferon score (P = 0.006), decrease in complement C3 level (P = 0.0001), the presence of anti‐DNA antibodies (P < 0.0001) and anti‐C1q antibodies (P = 0.004), and current or past history of nephritis (P = 0.02 and P = 0.003, respectively); and correlated inversely with age (r = −0.49, P < 0.0001). SLE patient sera also reacted with p40‐associated proteins. Conclusion: 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 toward SLE pathogenesis.
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Antibodies to the L1 ORF1 protein were identified in SLE patients with severe and active disease.
“A recent study identified antibodies to the L1 ORF1 protein in SLE patients with severe and active disease118.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [118]
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The role of retrotransposable elements in ageing and age-associated diseases
Gorbunova, V., Seluanov, A., Mita, P., McKerrow, W., Fenyö, D., Boeke, J. D., Linker, S. B., Gage, F. H., Kreiling, J. A., Petrashen, A. P., et al. (2021) · Nature · doi:10.1038/s41586-021-03542-y · Cited by 457 · see citing works
- Authors
- Carter, V., LaCava, J., Taylor, M. S., Liang, S. Y., Mustelin, C., Ukadike, K. C., Bengtsson, A., Lood, C., & Mustelin, T.
- Affiliations
- University of Washington (US)
- University Medical Center Groningen (NL)
- Massachusetts General Hospital (US)
- Lund University (SE)
- Corresponding author
- Mustelin, Tomas
- ORCID
- Venue
- Arthritis & Rheumatology
- Publisher
- Wiley
- Published
- 2019-12-27
- Volume
- 72
- Issue
- 1
- Pages
- 89-99
- ISSN
- 2326-5191 (ISSN-L)
- 2326-5205
- PMC
- PMC6935427
- OpenAlex
- W2963999797
- Cited by
- 41
- References
- 60
- Citations by year
- 2025: 7 · 2024: 6 · 2023: 10 · 2022: 5 · 2021: 10 · 2020: 2 · 2019: 1
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Arthritis & Rheumatology (publishedVersion, other-oa)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Center for Scientific Review (P41GM109824, R01GM126170, R21AR075134)
- Alliance for Lupus Research (519414)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Keywords
- systemic lupus erythematosus, LINE-1 retrotransposons, autoantibodies, long interspersed nuclear elements, autoantigens, disease activity, type I interferon, complement C3, anti-DNA antibodies, anti-C1q antibodies, lupus nephritis, disease flares, systemic sclerosis
- MeSH terms
- Age Factors, Antibodies, Antinuclear, Autoantibodies, Complement C3, DNA-Binding Proteins, Humans, Lupus Erythematosus, Systemic, Lupus Nephritis, Scleroderma, Systemic, Severity of Illness Index, Complement C1q, Case-Control Studies, Long Interspersed Nucleotide Elements
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