Etiopathogenesis of Systemic Lupus Erythematosus

Herrmann, Martin; Winkler, Thomas; Gaipl, Udo S.; Lorenz, Hanns‐Martin; Geiler, Thomas; Kalden, Joachim R.

doi:10.1159/000024421

Cited by 42 publications

(32 citation statements)

References 62 publications

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“…Therefore, we can speculate that GCs may have a protective effect as regards functional retinal impairment assessed by fundus perimetry. It is well known that the prevalence of retinopathy has reduced dramatically since the introduction of corticosteroids in SLE treatment, from about half to just 10% of patients [2, 53]. The pathogenesis of retinopathy is mostly attributed to a vasculopathy, in particular microangiopathy [2, 54].…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that the prevalence of retinopathy has reduced dramatically since the introduction of corticosteroids in SLE treatment, from about half to just 10% of patients [2, 53]. The pathogenesis of retinopathy is mostly attributed to a vasculopathy, in particular microangiopathy [2, 54]. In our cohort, we did not detect evident signs of microangiopathy, although these alterations might be better demonstrated using angiographic techniques not actually performed in the absence of a clear clinical indication and as they are technically invasive.…”

Section: Discussionmentioning

confidence: 99%

“…Systemic lupus erythematosus (SLE) is a connective tissue disease that involves multiple organs [1, 2]. Ocular manifestations affecting multiple ocular structures can occur in SLE in up to one third of patients [3].…”

Section: Introductionmentioning

confidence: 99%

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Evidence for the Detection of Subclinical Retinal Involvement in Systemic Lupus Erythematosus and Sjögren Syndrome: A Potential Association with Therapies

Conigliaro

Triggianese

Draghessi

et al. 2018

Int Arch Allergy Immunol

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Background: Retinal involvement in systemic lupus erythematosus (SLE) and Sjögren syndrome (SS) may be subclinical and thus underdiagnosed. Objectives: We aimed at evaluating morphological and functional visual abnormalities in a cohort of SLE and SS patients in the absence of an overt clinical visual impairment. We also investigated potential associations between retinal disorders and disease activity, organ involvement, and treatment with steroid and/or hydroxychloroquine. Methods: The study comprised 42 SLE and 36 primary SS patients and 76 healthy controls (HC). Ophthalmological examination, standard automated perimetry, spectral-domain optical coherence tomography, and fundus perimetry were performed. Results: Retinal thickness of the posterior pole was not different between SLE and HC groups, but it was reduced in the SS group compared with both the HC and the SLE group. In SLE and SS patients, mean defect and pattern standard deviation by standard automated perimetry were higher than in HC. Visual field index values were lower in both SLE and SS patients than in HC. SLE patients with nephritis displayed increased mean defect and pattern standard deviation and reduced visual field index values compared to patients without nephritis. In SLE and SS patients, fundus perimetry differential sensitivity was reduced, and mean defect values were higher than in HC. Disturbances in fundus perimetry in the SLE group were more prevalent in steroid-naïve patients and in SS patients who received a cumulative hydroxychloroquine dose > 1,000 g. Conclusions: Functional eye impairment was demonstrated in SLE patients, possibly associated with kidney involvement. In SLE, corticosteroids might exert a protective role. Morphological alterations and functional impairment were detected in SS patients, which may be linked to hydroxychloroquine toxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Evidence for the Detection of Subclinical Retinal Involvement in Systemic Lupus Erythematosus and Sjögren Syndrome: A Potential Association with Therapies

Conigliaro

Triggianese

Draghessi

et al. 2018

Int Arch Allergy Immunol

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“…Auffällig ist weiterhin, dass die Veranlagung, einen SLE oder andere Autoimmunerkrankungen zu bekommen, in manchen Familien gehäuft vorkommt, so dass auf die Beteiligung genetischer Faktoren geschlossen werden kann (= Risikofaktor). Die beim SLE auftretenden Auto-Antikörper sind vor allem gegen Antigene der Zellkerne (= Antinukleäre Antikörper [ANA]) gerichtet [16].…”

Section: Das Krankmachende Prinzip (Etiopathogenese) Beruht Beim Sle unclassified

“…Ein Clearance-Defekt für sterbende Zellen ist mit der Entwicklung von SLE verknüpft [16,18]. Bei gesunden Menschen werden apoptotische Zellen durch Makrophagen so effizient beseitigt, dass ein Freisetzen intrazellulärer Bestandteile vermieden wird.…”

Section: Clearance Sterbender Zellenunclassified

Eine unzureichende Erkennung und Beseitigung von sterbenden Zellen kann zur Entstehung von chronischer Autoimmunität führen

2005

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Not properly cleared dead cells are dangerous for the body. The dead cells accumulate, lose their membrane integrity, danger signals are released, and nuclear antigens get accessible in an inflammatory context. In times of increased apoptosis, tolerance can be broken, a chronic inflammation results which then can lead to an autoimmune reaction against nuclear constituents. An impaired clearance of dying cells represents a central pathogenic process in the development of chronic autoimmune diseases like in systemic lupus erythematosus (SLE). Many adaptor molecules and receptors are involved in the clearance of dying cells. Complement components, serum DNase I, phosphatidylserine, and modified glycoproteins participate crucially in the clearance of apoptotic and necrotic cells. We further observed intrinsic defects of macrophages of some SLE patients. Macrophages as well as granulocytes of some SLE patients showed heterogeneous clearance defects. Furthermore, we observed an accumulation of nuclear material in germinal centres of lymph nodes of some SLE patients. The non-ingested nuclear material may provide survival signals for autoreactive B cells and consecutively antinuclear autoantibodies (ANA) will be produced. We therefore conclude that drugs promoting the phagocytosis are important candidates of specific therapies in the future which expect a more gentle and purposive treatment of patients with SLE.

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Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

Gaipl¹,

Beyer²,

Heyder³

et al. 2004

Arthritis & Rheumatism

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105

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Objective. The efficient uptake of dying cells by phagocytes is essential to the avoidance of chronic inflammation. Some human autoimmune responses are thought to be driven by autoantigens from apoptotic or necrotic cells. We analyzed the role of C1q and DNase I in the disposal of necrotic cell-derived chromatin because deficiencies in these serum factors predispose to the development of systemic autoimmune disorders, such as systemic lupus erythematosus.Methods. Human necrotic peripheral blood lymphocytes were incubated in cell culture medium supplemented with various sera or serum components. Chromatin degradation was monitored by measuring the residual DNA content by flow cytometry. The uptake of necrotic cell-derived nuclei was analyzed by in vitro phagocytosis assays.Results. Reconstitution of C1q-depleted serum with C1q strongly increased its ability to degrade necrotic cell-derived chromatin. Although C1q itself displayed no DNase activity, it strongly augmented the activity of serum DNase I. Whereas an excess of recombinant DNase I degraded chromatin in the absence of C1q, efficient uptake of the predigested material by monocyte-derived phagocytes required the presence of C1q. These data show that C1q and DNase I cooperate in the degradation of chromatin from necrotic cells. Furthermore, C1q was found to be necessary for effective uptake of degraded chromatin by monocyte-derived phagocytes.Conclusion. C1q or DNase I deficiencies may precipitate autoimmunity in humans by a mechanism similar to that of other molecules that are involved in the safe, efficient, and rapid disposal of dying cells.

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Etiopathogenesis of Systemic Lupus Erythematosus

Cited by 42 publications

References 62 publications

Evidence for the Detection of Subclinical Retinal Involvement in Systemic Lupus Erythematosus and Sjögren Syndrome: A Potential Association with Therapies

Evidence for the Detection of Subclinical Retinal Involvement in Systemic Lupus Erythematosus and Sjögren Syndrome: A Potential Association with Therapies

Eine unzureichende Erkennung und Beseitigung von sterbenden Zellen kann zur Entstehung von chronischer Autoimmunität führen

Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

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