Nandakumar Kutty Selva, Collin Mattias, Olsén Arne, Nimmerjahn Falk, Blom Anna M, Ravetch Jeffrey V, Holmdahl Rikard
Medical Inflammation Research, Lund University, Lund, Sweden.
Eur J Immunol. 2007 Oct;37(10):2973-82. doi: 10.1002/eji.200737581.
The glycosylation status of IgG has been implicated in the pathology of rheumatoid arthritis. Earlier, we reported the identification of a novel secreted endo-beta-N-acetylglucosaminidase (EndoS), secreted by Streptococcus pyogenes that specifically hydrolyzes the beta-1,4-di-N-acetylchitobiose core of the asparagine-linked glycan of human IgG. Here, we analyzed the arthritogenicity of EndoS-treated collagen type II (CII)-specific mouse mAb in vivo. Endoglycosidase treatment of the antibodies inhibited the induction of arthritis in (BALB/c x B10.Q) F1 mice and induced a milder arthritis in B10.RIII mice as compared with the severe arthritis induced by non-treated antibodies. Furthermore, EndoS treatment did not affect the binding of IgG to CII and their ability to activate complement, but it resulted in reduced IgG binding to FcgammaR and disturbed the formation of stable immune complexes. Hence, the asparagine-linked glycan on IgG plays a crucial role in the development of arthritis.
IgG的糖基化状态与类风湿性关节炎的病理过程有关。此前，我们报道了一种由化脓性链球菌分泌的新型分泌型内切β-N-乙酰氨基葡萄糖苷酶（EndoS），它能特异性水解人IgG天冬酰胺连接聚糖的β-1,4-二-N-乙酰壳二糖核心。在此，我们分析了EndoS处理的II型胶原（CII）特异性小鼠单克隆抗体在体内的致关节炎性。与未处理抗体诱导的严重关节炎相比，用内切糖苷酶处理抗体可抑制（BALB/c×B10.Q）F1小鼠关节炎的诱导，并在B10.RIII小鼠中诱导出较轻的关节炎。此外，EndoS处理不影响IgG与CII的结合及其激活补体的能力，但导致IgG与FcγR的结合减少，并干扰稳定免疫复合物的形成。因此，IgG上的天冬酰胺连接聚糖在关节炎的发展中起关键作用。
