Journal
JOURNAL OF IMMUNOLOGY
Volume 187, Issue 1, Pages 561-569Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1100467
Keywords
-
Categories
Ask authors/readers for more resources
Human studies using Abs to two different, nonoverlapping epitopes of IL-13 suggested that epitope specificity can have a clinically significant impact on clearance of IL-13. We propose that Ab modulation of IL-13 interaction with IL-13R alpha 2 underlies this effect. Two Abs were administered to healthy subjects and mild asthmatics in separate dose-ranging studies and allergen-challenge studies. IMA-638 allows IL-13 interaction with IL-13R alpha 1 or IL-13R alpha 2 but blocks recruitment of IL-4R alpha to the IL-13/IL-13R alpha 1 complex, whereas IMA-026 competes with IL-13 interaction with IL-13R alpha 1 and IL-13R alpha 2. We found similar to 10-fold higher circulating titer of captured IL-13 in subjects treated with IMA-026 compared with those administered IMA-638. To understand how this difference could be related to epitope, we asked whether either Ab affects IL-13 internalization through cell surface IL-13R alpha 2. Humans inducibly express cell surface IL-13R alpha 2 but lack the soluble form that regulates IL-13 responses in mice. Cells with high IL-13R alpha 2 expression rapidly and efficiently depleted extracellular IL-13, and this activity persisted in the presence of IMA-638 but not IMA-026. The potency and efficiency of this clearance pathway suggest that cell surface IL-13R alpha 2 acts as a scavenger for IL-13. These findings could have important implications for the design and characterization of IL-13 antagonists. The Journal of Immunology, 2011, 187: 561-569.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available