IgG and IgA Autoantibodies Against L1 ORF1p Expressed in Granulocytes Correlate with Granulocyte Consumption and Disease Activity in Pediatric Systemic Lupus Erythematosus

Kennedy Ukadike¹, Kathryn Ni¹, Victoria Carter¹, Martin Taylor², John LaCava³, Lauren Pachman⁴, Xiaoxing Wang¹, Mary Eckert⁵, Anne Stevens¹, Christian Lood¹ and Tomas Mustelin¹, ¹University of Washington, Seattle, WA, ²Massachusetts General Hospital, Boston, MA, ³Rockefeller University, New York, NY, ⁴Department of Pediatrics, Northwestern University Feinberg School of Medicine; The Ann and Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Rheumatology; The CureJM Center of Excellence in Juvenile Myositis Research and Care, The Stanley Manne Children's Research Center of Chicago, Lake Forest, IL, ⁵Seattle Children's Hospital, Seattle, WA

Meeting: ACR Convergence 2020

Keywords: Autoantibody(ies), Disease Activity, interferon, neutrophils, Systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 9, 2020

Title: SLE – Diagnosis, Manifestations, & Outcomes Poster III: Bench to Bedside

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.

Anti-p40 and disease state correlations

Anti-p40 and disease activity correlations

Neutrophil activation and disease state correlations

Disclosure: K. Ukadike, None; K. Ni, None; V. Carter, None; M. Taylor, None; J. LaCava, None; L. Pachman, Reveragen, 2; X. Wang, None; M. Eckert, None; A. Stevens, None; C. Lood, None; T. Mustelin, None.

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 .

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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/