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Prevention of murine antiphospholipid syndrome by BAFF blockade.
- Source :
-
Arthritis and rheumatism [Arthritis Rheum] 2008 Sep; Vol. 58 (9), pp. 2824-34. - Publication Year :
- 2008
-
Abstract
- Objective: This study was undertaken to determine whether BAFF blockade can be used to prevent or treat antiphospholipid syndrome in a mouse model.<br />Methods: Eight- and 12-week-old (NZW x BXSB)F(1) mice were treated with BAFF-R-Ig or TACI-Ig alone or in addition to a short course of CTLA-4Ig. Mice were monitored for thrombocytopenia and proteinuria. Sera were tested for anticardiolipin antibodies (aCL), BAFF levels, and levels of soluble vascular cell adhesion molecule and E-selectin. Mice were killed at 17, 22, or 32 weeks of age, and kidneys and hearts were subjected to histologic examination. Spleen cells were phenotyped and enzyme-linked immunospot assays for autoantibody-producing B cells were performed.<br />Results: Both BAFF-R-Ig and TACI-Ig prevented disease onset and significantly prolonged survival. Treated mice had significantly smaller spleens than controls, with fewer B cells and fewer activated and memory T cells. BAFF blockade did not prevent the development of aCL, and there was only a modest delay in the development of thrombocytopenia. However, treated mice had significantly less nephritis and myocardial infarcts than did controls.<br />Conclusion: Our findings suggest that aCL are generated in the germinal center, which is relatively independent of BAFF. Effector function of antiplatelet antibodies was only modestly affected by BAFF blockade. In contrast, myocardial infarctions were prevented, suggesting that triggering of thromboses requires both autoantibodies and mediators of inflammation. Similarly, renal damage requires both immune complexes and effector cells. The dissociation between autoantibody production and inflammation that may occur with B cell-depleting therapies underscores the role of B cells as effector cells in the autoimmune response.
- Subjects :
- Animals
Antiphospholipid Syndrome immunology
Antiphospholipid Syndrome metabolism
Autoimmunity immunology
B-Cell Activating Factor immunology
B-Cell Activation Factor Receptor antagonists & inhibitors
B-Cell Activation Factor Receptor immunology
B-Lymphocytes cytology
B-Lymphocytes immunology
B-Lymphocytes metabolism
Cardiolipins immunology
Cardiolipins metabolism
Disease Models, Animal
E-Selectin metabolism
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Immunohistochemistry
Kaplan-Meier Estimate
Kidney immunology
Kidney metabolism
Male
Mice
Myocardium immunology
Myocardium metabolism
Proteinuria immunology
Proteinuria pathology
Reverse Transcriptase Polymerase Chain Reaction
Spleen cytology
Spleen immunology
Spleen metabolism
Staining and Labeling
Statistics, Nonparametric
Vascular Cell Adhesion Molecule-1 metabolism
Antiphospholipid Syndrome prevention & control
Autoantibodies immunology
B-Cell Activating Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-0131
- Volume :
- 58
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Arthritis and rheumatism
- Publication Type :
- Academic Journal
- Accession number :
- 18759321
- Full Text :
- https://doi.org/10.1002/art.23764