Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/65801
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Type: Journal article
Title: Exposure and binding of selected immunodominant La/SSB epitopes on human apoptotic cells
Author: Neufing, P.
Clancy, R.
Jackson, M.
Tran, H.
Buyon, J.
Gordon, T.
Citation: Arthritis and Rheumatism, 2005; 52(12):3934-3942
Publisher: Wiley-Liss
Issue Date: 2005
ISSN: 0004-3591
1529-0131
Statement of
Responsibility: 
Petra J. Neufing, Robert M. Clancy, Michael W. Jackson, Hai Bac Tran, Jill P. Buyon, and Tom P. Gordon
Abstract: <h4>Objective</h4>Opsonization of apoptotic cells by autoantibodies bound to surface membrane-translocated La/SSB antigens may initiate tissue damage in the setting of congenital heart block. By injecting pregnant mice with human anti-La antibodies, we previously demonstrated the formation of IgG-apoptotic cell complexes in the developing mouse fetus; however, the binding of anti-La antibodies to human-specific epitopes could not be addressed. Accordingly, the objective of the current study was to delineate the epitope specificity of human La antibodies that are exposed on the surface of apoptotic cells.<h4>Methods</h4>We used fluorescence microscopy and flow cytometry to assess the binding of human anti-La antibodies affinity purified against immunodominant epitopes of La to human cells undergoing spontaneous apoptosis, in a murine xenograft model in vivo and in cultured human fetal cardiocytes rendered apoptotic in vitro, respectively.<h4>Results</h4>Anti-La antibodies bound to immunodominant epitopes of La within the NH(2)-terminus and the RNA recognition motif (RRM) region of apoptotic human cells, in both xenografts and fetal cardiocytes. In contrast, human antibodies affinity purified against the COOH-terminal La epitope did not bind apoptotic cells in either model. This defines the topology of redistributed La during apoptosis, with surface exposure of the NH(2)-terminus and RRM regions. The potential importance of anti-La NH(2)-terminal and anti-La RRM specificity was confirmed by detection of this reactivity in mothers of children with congenital heart block.<h4>Conclusion</h4>These findings provide insight into both the molecular modification of the La autoantigen during apoptosis and the specificity of antibodies capable of binding to surface-exposed La. Subsequent formation of surface immune complexes may lead to tissue injury in patients with autoimmune diseases such as congenital heart block.
Keywords: Cells, Cultured
Myocytes, Cardiac
Animals
Mice, Inbred BALB C
Humans
Mice
Sjogren's Syndrome
Heart Block
Lupus Erythematosus, Systemic
Ribonucleoproteins
Antibodies, Antinuclear
Autoantigens
Epitopes
Immunodominant Epitopes
Transplantation, Heterologous
In Situ Nick-End Labeling
Apoptosis
Protein Structure, Tertiary
Female
Male
Rights: Copyright © 2005 by the American College of Rheumatology
DOI: 10.1002/art.21486
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