Date: Monday, November 9, 2020
Session Type: Poster Session D
Session Time: 9:00AM-11:00AM
Background/Purpose: To quantitate autoantibodies against the RNA-binding p40 (ORF1p) protein encoded by the L1 retroelement, expression of p40 itself, and markers of neutrophil death in patients with pediatric systemic lupus erythematosus (pSLE), and to determine if correlations exist between these and disease activity.
Methods: Autoantibodies in the plasma of pSLE patients (n=30), healthy children (n=37), and disease controls juvenile idiopathic arthritis (JIA) (n=32) and juvenile dermatomyositis (JDM) (n=60), were measured by ELISA. Expression of p40 in immune cells was assessed by immunoblotting and flow cytometry. Markers of neutrophil activation were quantitated by ELISA.
Results: IgG and IgA autoantibodies reactive with p40 were detected in the pSLE patients, but were low in healthy controls and in JIA or JDM. pSLE patients with active disease (13 of them newly diagnosed) had higher titers than the same patients after effective therapy (p=0.0003). IgG titers correlated with SLEDAI (r=0.65, p=0.0001), ESR (r=0.43, p=0.02), and anti-dsDNA antibodies (r=0.49, p< 0.03), and inversely with complement C3 (p=0.002) and C4 (p=0.006). p40 protein was detected in a subpopulation of CD66b+ granulocytes in pSLE, as well as in adult SLE patients. Myeloperoxidase and neutrophil elastase complexed with DNA and the neutrophil-derived S100A8/A9 were elevated in plasma from pSLE patients with active disease and correlated with anti-p40 autoantibodies and disease activity.
Conclusion: Children with active SLE have elevated IgG and IgA autoantibodies against L1 p40, a protein found in circulating granulocytes. P40 expression and autoantibody levels correlate with disease activity and suggest that neutrophils are a source of retroelement expression.
To cite this abstract in AMA style:Ukadike K, Ni K, Carter V, Taylor M, LaCava J, Pachman L, Wang X, Eckert M, Stevens A, Lood C, Mustelin T. IgG and IgA Autoantibodies Against L1 ORF1p Expressed in Granulocytes Correlate with Granulocyte Consumption and Disease Activity in Pediatric Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/igg-and-iga-autoantibodies-against-l1-orf1p-expressed-in-granulocytes-correlate-with-granulocyte-consumption-and-disease-activity-in-pediatric-systemic-lupus-erythematosus/. Accessed January 23, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/igg-and-iga-autoantibodies-against-l1-orf1p-expressed-in-granulocytes-correlate-with-granulocyte-consumption-and-disease-activity-in-pediatric-systemic-lupus-erythematosus/