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The Journal of Immunology, 2002, 169: 4314-4321.
Copyright © 2002 by The American Association of Immunologists

BLyS and APRIL Form Biologically Active Heterotrimers That Are Expressed in Patients with Systemic Immune-Based Rheumatic Diseases1

Viktor Roschke*, Svetlana Sosnovtseva*, Christopher D. Ward{dagger}, June S. Hong{dagger}, Rodger Smith*, Vivian Albert*, William Stohl, Kevin P. Baker{ddagger}, Stephen Ullrich§, Bernardetta Nardelli{dagger}, David M. Hilbert{dagger} and Thi-Sau Migone2,{dagger}

Departments of * Antibody Development, {dagger} Preclinical Development, {ddagger} Preclinical Discovery, and § Protein Development, Human Genome Sciences, Rockville, MD, 20850; and Division of Rheumatology, Department of Medicine, Los Angeles County and University of Southern California Medical Center and Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033

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.




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