Systemic Lupus Erythematosus
Opsonization of late apoptotic cells by systemic lupus erythematosus autoantibodies inhibits their uptake via an Fcγ receptor–dependent mechanism
Version of Record online: 28 SEP 2007
Copyright © 2007 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 56, Issue 10, pages 3399–3411, October 2007
How to Cite
Reefman, E., Horst, G., Nijk, M. T., Limburg, P. C., Kallenberg, C. G. M. and Bijl, M. (2007), Opsonization of late apoptotic cells by systemic lupus erythematosus autoantibodies inhibits their uptake via an Fcγ receptor–dependent mechanism. Arthritis & Rheumatism, 56: 3399–3411. doi: 10.1002/art.22947
- Issue online: 28 SEP 2007
- Version of Record online: 28 SEP 2007
- Manuscript Accepted: 29 JUN 2007
- Manuscript Received: 19 JUN 2006
- Dutch Kidney Foundation
Decreased clearance of apoptotic cells is suggested to be a major pathogenic factor in systemic lupus erythematosus (SLE). The aim of this study was to investigate whether the binding of SLE autoantibodies to apoptotic cells influences the phagocytosis of these cells by macrophages.
Apoptosis was induced in a human T cell line (Jurkat) and a keratinocyte cell line (HaCaT) by ultraviolet B irradiation. Binding of purified IgG from 26 SLE patients and 15 healthy controls to apoptotic cells was assessed by flow cytometry and Western blotting. Phagocytosis of IgG-opsonized apoptotic cells by monocyte-derived macrophages was assessed by light microscopy. Similar experiments were performed with a monoclonal antibody against SSA/Ro and IgG fractions from 5 patients with Sjögren's syndrome (SS) and 5 patients with rheumatoid arthritis (RA).
IgG fractions from all 26 SLE patients bound to late apoptotic, but not early apoptotic, cells. IgG fractions isolated from SLE patients with different autoantibody profiles showed comparable levels of binding. IgG fractions from healthy controls did not bind. Opsonization of apoptotic cells with IgG fractions from SLE patients resulted in a significant inhibition of phagocytosis as compared with healthy control IgG fractions. A monoclonal antibody directed against SSA/Ro and IgG isolated from 5 antinuclear antibody (ANA)–positive patients with SS were also able to elicit these effects, whereas IgG from 5 ANA-negative patients with RA did not. The inhibitory effect of patient IgG was abolished by blocking either the Fcγ receptors (FcγR) or the constant region of IgG, using a specific Fc-blocking peptide.
Autoantibodies from SLE patients are able to opsonize apoptotic cells and inhibit their uptake by macrophages via an FcγR-dependent mechanism.