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Clearance deficiency and systemic lupus erythematosus (SLE)
Abstract
Systemic lupus erythematosus (SLE) is a fairly heterogeneous autoimmune disease. Impaired clearance functions for dying cells may explain accumulation of nuclear autoantigens in various tissues of SLE patients. Our data show that in a subgroup of patients with SLE, apoptotic cells accumulated in the germinal centres of the lymph nodes. Apoptotic material was attached to the surfaces of follicular dendritic cells. Furthermore, we found an accumulation of apoptotic cells in the skin of patients with cutaneous lupus after UV exposure. Granulocytes and monocytes in whole blood of SLE patients showed a reduced uptake of albumin- and polyglobin-coated beads. Furthermore, we analysed sera from SLE patients in migration assays and observed that the attraction signals for macrophages were reduced by sera of approximately 25% of the SLE patients. Analyses of high-affinity DNA binding IgG autoantibodies of SLE patients revealed that those antibodies had gained their DNA reactivity in a germinal centre reaction. We suggest a stepwise maturation from a non-anti-DNA reactive B cell to an anti-dsDNA autoreactive B cell. We conclude that impaired clearance in early phases of apoptosis leads to a secondary necrotic status of the cells. Danger signals are released; modified autoantigens are accessible, favouring an autoimmune reaction.
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“DAMPs are released from dying cells and induce immune responses to cellular antigens whether the cell is a tumor cell, autologous tissue or infected with a pathogen.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [4]
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Immunogenic and tolerogenic cell death
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“In addition, debris from non-transformed cells in some settings can stimulate organ-specific or general autoimmune response”
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“Not surprisingly then, defects in these TAM-dependent processes are associated with the development of human autoimmune diseases (Gaipl et al. 2007; Shao and Cohen 2011), and autoimmune phenotypes are prominent features of the TAM mouse mutants (Scott et al.”
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“Is an intriguing model to study the cross-presentation of antigens associated with dying cells, because defective clearance of cell debris, development of anti-nuclear antibodies, and increased bioavailability of type I IFN all represent hallmarks of the disease (4, 78).”
BackgroundImmunopathogenic mechanisms of systemic autoimmune disease
Wahren‐Herlenius, M., & Dörner, T. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60954-x · Cited by 597
Apoptotic Cell-Derived Extracellular Vesicles: More Than Just Debris
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Metadata
- Authors
- Gaipl, U. S., Munoz, L. E., Grossmayer, G., Lauber, K., Franz, S., Sarter, K., Voll, R. E., Winkler, T., Kuhn, A., Kalden, J., Kern, P., & Herrmann, M.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University of Tübingen (DE)
- Heinrich Heine University Düsseldorf (DE)
- ORCID
- Venue
- Journal of Autoimmunity
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 28
- Issue
- 2-3
- Pages
- 114-121
- ISSN
- 0896-8411 (ISSN-L)
- OpenAlex
- W2021273693
- Cited by
- 277
- References
- 56
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 10 · 2019: 12 · 2018: 11 · 2017: 18 · 2016: 14 · 2015: 18 · 2014: 25 · 2013: 21 · 2012: 19
- FWCI
- 18.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Autoimmunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
- Keywords
- systemic lupus erythematosus, efferocytosis, germinal center, follicular dendritic cells, cutaneous lupus erythematosus, UV-induced apoptosis, macrophage migration, anti-dsDNA antibodies, B cell maturation, damage-associated molecular patterns, nuclear autoantigens, secondary necrosis
- MeSH terms
- B-Lymphocytes, Humans, Immunohistochemistry, Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Systemic, Macrophages, Monocytes, Phagocytosis, Apoptosis, Models, Immunological, Germinal Center, In Situ Nick-End Labeling
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