Journal article
Antilymphocyte autoantibodies generate T cell-C4d signatures in systemic lupus erythematosus
Translational research : the journal of laboratory and clinical medicine, v 164(6), pp 496-507
01 Dec 2014
PMID: 25168018
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
T cells bearing C4d, a complement activation product (CAP), have been shown to be highly sensitive and specific as diagnostic biomarkers for systemic lupus erythematosus (SLE). T cells bearing C4d are also functionally abnormal, suggesting a role for cell-bound CAPs in lupus pathogenesis. However, the mechanism responsible for generation of T-C4d has not been determined. The purpose of this cross-sectional and prospective study was to investigate the potential role of anti-T-cell autoantibodies in the generation of the T cell-bound C4d (T-C4d) signatures in SLE. Briefly, T cells from patients with SLE (n = 326), patients with other inflammatory diseases (n = 185), and healthy controls (n = 48) were characterized for surface deposition of either or both of C4d and immunoglobulin (Ig) by flow cytometry. In vitro phenotype transfer experiments were performed to characterize Ig from patients with SLE for the capacity to generate T-C4d signatures in vitro. The results demonstrate that individual patients with SLE harbor specific signatures reflecting the presence of either or both of C4d and Ig on their T cells and T-cell subsets. In addition, SLE patient-specific signatures can be transferred in vitro to normal T cells by exposure to Ig purified from the signature donor. Complement activation does not proceed through the generation of C5b-9 (membrane attack complex) or cellular lysis, and T-C4d does not correlate with lymphopenia. In conclusion, these results suggest that patient-specific T-C4d signatures are generated by anti-T-cell autoantibodies that trigger sublytic complement activation, a previously unrecognized pathway in lupus pathogenesis.
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Details
- Title
- Antilymphocyte autoantibodies generate T cell-C4d signatures in systemic lupus erythematosus
- Creators
- Chau-Ching LiuSusan Manzi - Allegheny Health NetworkJoseph M Ahearn - Temple University
- Publication Details
- Translational research : the journal of laboratory and clinical medicine, v 164(6), pp 496-507
- Publisher
- Elsevier
- Grant note
- R01 AI077591 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Medicine (Graduate); General Internal Medicine
- Web of Science ID
- WOS:000345197100007
- Scopus ID
- 2-s2.0-84910653984
- Other Identifier
- 991021934001804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Medical Laboratory Technology
- Medicine, Research & Experimental