Brain-reactive autoantibodies in neuropsychiatric systemic lupus erythematosus Article Swipe
Cristina Cocco
,
Elias Manca
,
G Corda
,
Maria Maddalena Angioni
,
Barbara Noli
,
Mattia Congia
,
Francesco Loy
,
Michela Isola
,
Elisabetta Chessa
,
Alberto Floris
,
Lorena Lorefice
,
Luca Saba
,
Alessandro Mathieu
,
Gian‐Luca Ferri
,
Alberto Cauli
,
Matteo Piga
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2023.1157149
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2023.1157149
Introduction The pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) is widely unknown, and the role of autoantibodies is still undetermined. Methods To identify brain-reactive autoantibodies possibly related to NPSLE, immunofluorescence (IF) and transmission electron microscopy (TEM) on rat and human brains were performed. ELISA was used to reveal the presence of known circulating autoantibodies, while western blot (WB) was applied to characterize potential unknown autoantigen(s). Results We enrolled 209 subjects, including patients affected by SLE (n=69), NPSLE (n=36), Multiple Sclerosis (MS, n=22), and 82 age- and gender-matched healthy donors (HD). Autoantibody reactivity by IF was observed in almost the entire rat brain (cortex, hippocampus, and cerebellum) using sera from NPSLE and SLE patients and was virtually negative in MS and HD. NPSLE showed higher prevalence (OR 2.4; p = 0.047), intensity, and titer of brain-reactive autoantibodies than SLE patients. Most of the patient sera with brain-reactive autoantibodies (75%) also stained human brains. Double staining experiments on rat brains mixing patients’ sera with antibodies directed against neuronal (NeuN) or glial markers showed autoantibody reactivity restricted to NeuN-containing neurons. Using TEM, the targets of brain-reactive autoantibodies were located in the nuclei and, to a lesser extent, in the cytoplasm and mitochondria. Given the high degree of colocalization between NeuN and brain-reactive autoantibodies, we assumed NeuN was a possible autoantigen. However, WB analysis with HEK293T cell lysates expressing or not expressing the gene encoding for NeuN protein (RIBFOX3) showed that patients’ sera carrying brain-reactive autoantibodies did not recognize the NeuN corresponding band size. Among the panel of NPSLE-associated autoantibodies (e.g., anti-NR2, anti-P-ribosomal protein, antiphospholipid) investigated by ELISA assay, only the anti-β2-glycoprotein-I (aβ2GPI) IgG was exclusively found in those sera containing brain-reactive autoantibodies. Conclusion In conclusion, SLE and NPSLE patients possess brain-reactive autoantibodies but with higher frequency and titers found in NPSLE patients. Although many target antigens of brain-reactive autoantibodies are still undetermined, they likely include β2GPI.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2023.1157149
- https://www.frontiersin.org/articles/10.3389/fimmu.2023.1157149/pdf?isPublishedV2=False
- OA Status
- gold
- Cited By
- 26
- References
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- Related Works
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- OpenAlex ID
- https://openalex.org/W4380629884
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4380629884Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fimmu.2023.1157149Digital Object Identifier
- Title
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Brain-reactive autoantibodies in neuropsychiatric systemic lupus erythematosusWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
-
2023-06-13Full publication date if available
- Authors
-
Cristina Cocco, Elias Manca, G Corda, Maria Maddalena Angioni, Barbara Noli, Mattia Congia, Francesco Loy, Michela Isola, Elisabetta Chessa, Alberto Floris, Lorena Lorefice, Luca Saba, Alessandro Mathieu, Gian‐Luca Ferri, Alberto Cauli, Matteo PigaList of authors in order
- Landing page
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https://doi.org/10.3389/fimmu.2023.1157149Publisher landing page
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https://www.frontiersin.org/articles/10.3389/fimmu.2023.1157149/pdf?isPublishedV2=FalseDirect link to full text PDF
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
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https://www.frontiersin.org/articles/10.3389/fimmu.2023.1157149/pdf?isPublishedV2=FalseDirect OA link when available
- Concepts
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Autoantibody, NeuN, Medicine, Immunology, Human brain, Pathogenesis, Lupus erythematosus, Pathology, Antibody, Immunohistochemistry, PsychiatryTop concepts (fields/topics) attached by OpenAlex
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26Total citation count in OpenAlex
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2025: 10, 2024: 15, 2023: 1Per-year citation counts (last 5 years)
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39Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| primary_location.pdf_url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1157149/pdf?isPublishedV2=False |
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| primary_location.raw_source_name | Frontiers in Immunology |
| primary_location.landing_page_url | https://doi.org/10.3389/fimmu.2023.1157149 |
| publication_date | 2023-06-13 |
| publication_year | 2023 |
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