Session Type: Poster Session (Tuesday)
Session Time: 9:00AM-11:00AM
Background/Purpose: The long interspersed nuclear element 1 (LINE-1) has two major open reading frames (ORFs): ORF1 encodes the RNA-binding p40 protein, and ORF2 encodes the endonuclease and reverse transcriptase; both are 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 whether 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 SLE patients (n=172 total), disease controls (systemic sclerosis, n=20), and age-matched healthy subjects (n=78) by immunoblotting and ELISA. To determine the relationship between disease activity and LINE-1 p40 antibodies, the same SLE patients (n=80) were recruited at two time-points: low disease activity (median SLEDAI 2) and high disease activity (median SLEDAI 8.5). The patients were primarily female (89%), Caucasian (100%), with a median age of 44. An additional cross-sectional SLE cohort (n=12) was included to study LINE-1 p40 reactivity using Western blot. Preparations of p40 that also contained associated proteins were analyzed by immunoblotting with patient sera. Serum type I interferon (IFN) activity was analyzed using a cell reporter system (WISH). The 90th percentile of healthy controls was used as a cut-off for LINE-1 p40 positivity. GraphPad Prism and IBM SPSS were used for statistical analyses, and all analyses were considered statistically significant only if p< 0.05.
Results: Antibodies reactive with p40 were detected in the majority of patients and many healthy controls (Figure 1): they were higher in patients with SLE, but not systemic sclerosis, compared to healthy subjects (p=0.01, Figure 2). The anti-p40 reactivity was higher in patients during a flare than in remission (p=0.03, Figure 2), correlated with SLEDAI (p=0.0002), type I IFN 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, Figure 3), and they 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 towards SLE pathogenesis.
To cite this abstract in AMA style:Ukadike K, Carter V, LaCava J, Taylor M, Bengtsson A, Lood C, Mustelin T. High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements (LINE-1) in SLE [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/high-prevalence-and-disease-correlation-of-autoantibodies-against-p40-encoded-by-long-interspersed-nuclear-elements-line-1-in-sle/. Accessed December 5, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/high-prevalence-and-disease-correlation-of-autoantibodies-against-p40-encoded-by-long-interspersed-nuclear-elements-line-1-in-sle/