Anti-C1q Autoantibodies from Systemic Lupus Erythematosus Patients Enhance CD40-CD154-mediated Inflammation in Peripheral Blood Mononuclear Cells

Overview

Journal Clin Transl Immunology

Specialty Allergy & Immunology

Date 2022 Aug 5

PMID 35928801

Authors

Pascal Alexander Rabatscher

Marten Trendelenburg

Affiliations

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Abstract

Objectives: Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease with complex pathogenic mechanisms. Complement C1q has been shown to play a major role in SLE, and autoantibodies against C1q (anti-C1q) are strongly associated with SLE disease activity and severe lupus nephritis suggesting a pathogenic role for anti-C1q. Whereas C1q alone has anti-inflammatory effects on human monocytes and macrophages, C1q/anti-C1q complexes favor a pro-inflammatory phenotype. This study aimed to elucidate the inflammatory effects of anti-C1q on peripheral blood mononuclear cells (PBMCs).

Methods: Isolated monocytes, isolated T cells and bulk PBMCs of healthy donors with or without concomitant T cell activation were exposed to C1q or complexes of C1q and SLE patient-derived anti-C1q (C1q/anti-C1q). Functional consequences of C1q/anti-C1q on cells were assessed by determining cytokine secretion, monocyte surface marker expression, T cell activation and proliferation.

Results: Exposure of isolated T cells to C1q or C1q/anti-C1q did not affect their activation and proliferation. However, unspecific T cell activation in PBMCs in the presence of C1q/anti-C1q resulted in increased TNF, IFN-γ and IL-10 secretion compared with C1q alone. Co-culture and inhibition experiments showed that the inflammatory effect of C1q/anti-C1q on PBMCs was due to a direct CD40-CD154 interaction between activated T cells and C1q/anti-C1q-primed monocytes. The CD40-mediated inflammatory reaction of monocytes involves TRAF6 and JAK3-STAT5 signalling.

Conclusion: In conclusion, C1q/anti-C1q have a pro-inflammatory effect on monocytes that depends on T cell activation and CD40-CD154 signalling. This signalling pathway could serve as a therapeutic target for anti-C1q-mediated inflammation.

Citing Articles

Macrophages Unmasked: Their Pivotal Role in Driving Atherosclerosis in Systemic Lupus Erythematosus.

Wang C, Chen B, Yu X, Guan X Clin Rev Allergy Immunol. 2025; 68(1):10.

PMID: 39920534 DOI: 10.1007/s12016-025-09025-6.

Autoantibodies against Complement Classical Pathway Components C1q, C1r, C1s and C1-Inh in Patients with Lupus Nephritis.

Radanova M, Vasilev V, Mihaylova G, Kosturkova M, Kishore U, Roumenina L Int J Mol Sci. 2022; 23(16).

PMID: 36012546 PMC: 9409282. DOI: 10.3390/ijms23169281.

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