Basic Science
Abstract # 714: C-Reactive Protein Regulates the Interferon Response to Immune Complexes Containing snRNPs
Authors: Carolyn Mold, Rufus W. Burlingame, Terry W. Du Clos. University of New Mexico, Albuquerque, NM; INOVA Diagnostics Inc., San Diego, CA; VA Medical Center, Albuquerque, NM
Objective: The involvement of nucleic acid:protein autoantigen containing immune complexes (ICs) in the pathogenesis of SLE is well known, and the capacity of these ICs to induce plasmacytoid DCs to release interferon- via TLR-dependent pathways has recently been described. One of the primary acute phase reactants, C-reactive protein (CRP), can bind both chromatin and snRNPs (both target autoantigens in SLE), and promotes the uptake of apoptotic cells in mouse models. The authors therefore asked whether CRP could mediate the uptake and clearance of autoantigens and ICs in human cells.
Methods: Normal human PBMCs were incubated with purified snRNPs or apoptotic cells in vitro for 24 hrs in the presence or absence of anti-RNP antibodies and CRP. Cytokine responses were measured by ELISA.
Results: Only PBMCs incubated with all of the components required for IC formation (antigen and antibody) produced pro-inflammatory cytokines; the addition of CRP was able to suppress this cytokine release. CRP was able to mediate the release of the anti-inflammatory cytokine IL-10, even in the absence of monocytes, thus suggesting a direct role on DCs by CRP in mediating its anti-inflammatory effects.
Significance: The finding that one of the most common acute phase reactants was able to suppress IC-mediated pro-inflammatory cytokine release is fascinating, demonstrating an important protective role for the inflammatory response in protecting against self-reactivity in the face of external stimuli, such as infection. Whether the anti-inflammatory effects of CRP can be utilized therapeutically remains to be seen, but the notion of CRP mediated IL-10 release providing a buffer against IC-mediated DC activation via TLR ligation is fascinating.
