Anti-C1q Autoantibodies from Systemic Lupus Erythematosus Patients Induce a Proinflammatory Phenotype in Macrophages

Thanei, S. and Trendelenburg, M.. (2016) Anti-C1q Autoantibodies from Systemic Lupus Erythematosus Patients Induce a Proinflammatory Phenotype in Macrophages. J Immunol, 196 (5). pp. 2063-2074.

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Official URL: https://edoc.unibas.ch/62490/

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Anti-C1q autoantibodies (anti-C1q) are frequently found in patients with systemic lupus erythematosus (SLE) and correlate with the occurrence of proliferative lupus nephritis. A previous study of anti-C1q in experimental lupus nephritis demonstrated an important role for FcgammaRs in the pathogenesis of lupus nephritis, suggesting a direct effect on phagocytes. Therefore, we developed an in vitro model to study the effect of SLE patient-derived anti-C1q bound to immobilized C1q (imC1q) on human monocyte-derived macrophages (HMDMs) obtained from healthy donors and SLE patients. HMDMs were investigated by analyzing the cell morphology, LPS-induced cytokine profile, surface marker expression, and phagocytosis rate of apoptotic Jurkat cells. Morphologically, bound anti-C1q induced cell aggregations of HMDMs compared with imC1q or IgG alone. In addition, anti-C1q reversed the effect of imC1q alone, shifting the LPS-induced cytokine release toward a proinflammatory response. FcgammaR-blocking experiments revealed that the secretion of proinflammatory cytokines was mediated via FcgammaRII. The anti-C1q-induced inflammatory cytokine profile was accompanied by a downregulation of CD163 and an upregulation of LPS-induced CD80, CD274, and MHC class II. Finally, HMDMs primed on bound anti-C1q versus imC1q alone displayed a significantly lower phagocytosis rate of early and late apoptotic cells accompanied by a reduced Mer tyrosine kinase expression. Interestingly, anti-C1q-dependent secretion of proinflammatory cytokines was similar in SLE patient-derived cells, with the exception that IL-10 was slightly increased. In conclusion, anti-C1q induced a proinflammatory phenotype in HMDMs reversing the effects of imC1q alone. This effect might exacerbate underlying pathogenic mechanisms in lupus nephritis.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Clinical Immunology (Trendelenburg)
UniBasel Contributors:Trendelenburg, Marten
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1550-6606 (Electronic) 0022-1767 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 May 2020 07:58
Deposited On:25 May 2020 07:58

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