Dominant suppression of inflammation by glycan-hydrolyzed IgG
pnas.org
Kutty Selva Nandakumara,1, Mattias Collinb, Kaisa E. Happonenc, Allyson M. Croxfordd, Susanna L. Lundströme, Roman A. Zubareve, Merrill J. Rowleyd, Anna M. Blomc, and Rikard Holmdahla Author Affiliations
aMedical Inflammation Research andeChemistry I Division, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden;bDivision of Infection Medicine, Department of Clinical Sciences, Lund University, 22184 Lund, Sweden;cDepartment of Laboratory Medicine Malmö, Lund University, 205 02 Malmö, Sweden; anddDepartment of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, AustraliaEdited by Raymond A. Dwek, University of Oxford, Oxford, United Kingdom, and accepted by the Editorial Board April 16, 2013 (received for review January 24, 2013)
AbstractA unique anti-inflammatory property of IgG, independent of antigen specificity, is described. IgG with modification of the heavy-chain glycan on asparagine 297 by the streptococcal enzyme endo-ß-N-acetylglucosaminidase (EndoS) induced a dominant suppression of immune complex (IC)-mediated inflammation, such as arthritis, through destabilization of local ICs by fragment crystallizable–fragment crystallizable (Fc-Fc) interactions. Small amounts (250 µg) of EndoS-hydrolyzed IgG were sufficient to inhibit arthritis in mice and most effective during the formation of ICs in the target tissue. The presence of EndoS-hydrolyzed IgG disrupted larger IC lattice formation both in vitro and in vivo, as visualized with anti-C3b staining. Neither complement binding in vitro nor antigen–antibody binding per se was affected. |
