Nandakumar Kutty Selva, Johansson Björn P, Björck Lars, Holmdahl Rikard
Lund University, Lund, Sweden.
Arthritis Rheum. 2007 Oct;56(10):3253-60. doi: 10.1002/art.22930.
To investigate whether IgG-degrading enzyme of Streptococcus pyogenes (IdeS), a bacterial cysteine endopeptidase that cleaves human IgG in the hinge region, can be used for blocking the development of arthritis.
Recombinant IdeS was purified and tested for specificity against mouse IgG. IdeS was injected intravenously into mice with collagen antibody-induced arthritis (CAIA), collagen-induced arthritis (CIA), or relapsing CIA, and its effects on arthritis development and severity were assessed.
IdeS efficiently cleaved mouse IgG2a/c and IgG3 in vitro. Even at low dosage (10 microg), IdeS specifically cleaved IgG2a in vivo without any apparent side effects. IdeS treatment efficiently blocked CAIA induced by IgG2a antibodies. No effect was observed when arthritis was induced with IgG2b anti-type II collagen antibodies; since IdeS does not cleave IgG2b, this indicated that IgG cleavage was the mechanism of action. IdeS treatment reduced the severity of arthritis if administered within 24 hours after the onset of clinical arthritis, but did not block ongoing severe arthritis. IdeS treatment also significantly prevented an antibody-induced relapse in mice that had chronic arthritis, and delayed the onset and reduced the severity of arthritis in classic CIA.
IdeS has therapeutic potential in IgG antibody-mediated autoimmune arthritis, representing a new and unique means of blocking pathogenic antibodies.
研究化脓性链球菌的IgG降解酶（IdeS），一种能在铰链区切割人IgG的细菌半胱氨酸内肽酶，是否可用于阻止关节炎的发展。
纯化重组IdeS并检测其对小鼠IgG的特异性。将IdeS静脉注射到患有胶原抗体诱导的关节炎（CAIA）、胶原诱导的关节炎（CIA）或复发性CIA的小鼠体内，并评估其对关节炎发展和严重程度的影响。
IdeS在体外能有效切割小鼠IgG2a/c和IgG3。即使在低剂量（10微克）时，IdeS在体内也能特异性切割IgG2a，且无明显副作用。IdeS治疗能有效阻断由IgG2a抗体诱导的CAIA。用IgG2b抗II型胶原抗体诱导关节炎时未观察到效果；由于IdeS不切割IgG2b，这表明IgG切割是其作用机制。如果在临床关节炎发作后24小时内给药，IdeS治疗可降低关节炎的严重程度，但不能阻断正在进行的严重关节炎。IdeS治疗还能显著预防慢性关节炎小鼠的抗体诱导复发，并延缓经典CIA中关节炎的发作并降低其严重程度。
IdeS在IgG抗体介导的自身免疫性关节炎中具有治疗潜力，代表了一种阻断致病抗体的新的独特方法。
