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Enhanced anti-serpin antibody activity inhibits autoimmune inflammation in type 1 diabetes.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2012 Jun 15; Vol. 188 (12), pp. 6319-27. Date of Electronic Publication: 2012 May 16. - Publication Year :
- 2012
-
Abstract
- Intracellular (clade B) OVA-serpin protease inhibitors play an important role in tissue homeostasis by protecting cells from death in response to hypo-osmotic stress, heat shock, and other stimuli. It is not known whether these serpins influence immunological tolerance and the risk for autoimmune diseases. We found that a fraction of young autoimmune diabetes-prone NOD mice had elevated levels of autoantibodies against a member of clade B family known as serpinB13. High levels of anti-serpinB13 Abs were accompanied by low levels of anti-insulin autoantibodies, reduced numbers of islet-associated T cells, and delayed onset of diabetes. Exposure to anti-serpinB13 mAb alone also decreased islet inflammation, and coadministration of this reagent and a suboptimal dose of anti-CD3 mAb accelerated recovery from diabetes. In a fashion similar to that discovered in the NOD model, a deficiency in humoral activity against serpinB13 was associated with early onset of human type 1 diabetes. These findings suggest that, in addition to limiting exposure to proteases within the cell, clade B serpins help to maintain homeostasis by inducing protective humoral immunity.
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 188
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 22593614
- Full Text :
- https://doi.org/10.4049/jimmunol.1200467