1. BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases
- Author
-
Stephen Ullrich, Rodger Smith, Kevin P. Baker, Viktor Roschke, David M. Hilbert, Svetlana Sosnovtseva, Christopher D. Ward, Thi-Sau Migone, Bernardetta Nardelli, William Stohl, June S. Hong, and Vivian R. Albert
- Subjects
Immunology ,Tumor Necrosis Factor Ligand Superfamily Member 13 ,Lymphocyte Activation ,Transfection ,Arthritis, Reactive ,Atacicept ,Receptors, Tumor Necrosis Factor ,Cell Line ,Arthritis, Rheumatoid ,Mice ,Immune system ,Heterotrimeric G protein ,Rheumatic Diseases ,medicine ,Tumor Cells, Cultured ,Immunology and Allergy ,Animals ,Humans ,Lupus Erythematosus, Systemic ,Spondylitis, Ankylosing ,Receptor ,BAFF receptor ,B-cell activating factor ,Cells, Cultured ,B-Lymphocytes ,Mice, Inbred BALB C ,Lupus erythematosus ,business.industry ,Tumor Necrosis Factor-alpha ,Arthritis, Psoriatic ,Membrane Proteins ,medicine.disease ,Polymyositis ,Tumor necrosis factor alpha ,Female ,business ,B-Cell Activation Factor Receptor - Abstract
BLyS and APRIL are two members of the TNF superfamily that are secreted by activated myeloid cells and have costimulatory activity on B cells. BLyS and APRIL share two receptors, TACI and BCMA, whereas a third receptor, BAFF-R, specifically binds BLyS. Both BLyS and APRIL have been described as homotrimeric molecules, a feature common to members of the TNF superfamily. In this study, we show that APRIL and BLyS can form active heterotrimeric molecules when coexpressed and that circulating heterotrimers are present in serum samples from patients with systemic immune-based rheumatic diseases. These findings raise the possibility that active BLyS/APRIL heterotrimers may play a role in rheumatic and other autoimmune diseases and that other members of the TNF ligand superfamily may also form active soluble heterotrimers.
- Published
- 2002