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IgG and IgA autoantibodies against L1 ORF1p expressed in granulocytes correlate with granulocyte consumption and disease activity in pediatric systemic lupus erythematosus
- Source :
- Arthritis Research & Therapy, ARTHRITIS RESEARCH & THERAPY, 23(1):153. BioMed Central Ltd., Arthritis Research & Therapy, Vol 23, Iss 1, Pp 1-13 (2021)
- Publication Year :
- 2021
- Publisher :
- BioMed Central, 2021.
-
Abstract
- Background Most patients with systemic lupus erythematosus (SLE) have IgG autoantibodies against the RNA-binding p40 (ORF1p) protein encoded by the L1 retroelement. This study tested if these autoantibodies are also present in children with pediatric SLE (pSLE) and if the p40 protein itself could be detected in immune cells. 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 flow cytometry. Markers of neutrophil activation and death 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 (r = -0.55, p = 0.002) and C4 (r = -0.51, 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. Conclusions Children with active SLE have elevated IgG and IgA autoantibodies against L1 p40, and this protein can be detected in circulating granulocytes in both pediatric and adult SLE patients. P40 expression and autoantibody levels correlate with disease activity. Markers of neutrophil activation and death also correlate with these autoantibodies and with disease activity, suggesting that neutrophils express L1 and are a source of p40.
- Subjects :
- 0301 basic medicine
Adult
Neutrophils
Arthritis
Diseases of the musculoskeletal system
Granulocyte
PERIPHERAL-BLOOD
PRIMARY SJOGRENS-SYNDROME
ACTIVATION
03 medical and health sciences
0302 clinical medicine
Immune system
REVERSE-TRANSCRIPTASE
medicine
Retrotransposon
Humans
Lupus Erythematosus, Systemic
Child
Juvenile dermatomyositis
Autoantibodies
030203 arthritis & rheumatology
RETROELEMENTS
biology
business.industry
Pediatric lupus erythematosus
SIGNATURE
Autoantibody
NEUTROPHIL EXTRACELLULAR TRAPS
DNA
medicine.disease
Immunoglobulin A
030104 developmental biology
medicine.anatomical_structure
RC925-935
Myeloperoxidase
Neutrophil elastase
Immunoglobulin G
Immunology
CELLS
Long interspersed nuclear element
biology.protein
I INTERFERON SYSTEM
Antibody
business
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 14786362 and 14786354
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Arthritis Research & Therapy
- Accession number :
- edsair.doi.dedup.....d9a16fba53c34ec7ab1c2839637ce45b