Collagen type II-specific monoclonal antibody-induced arthritis in mice - Description of the disease and the influence of age, sex, and genes
Collagen type II-specific monoclonal antibody-induced arthritis in mice - Description of the disease and the influence of age, sex, and genes
复制标题
DOI：
10.1016/s0002-9440(10)63542-0
复制
发表时间：
2003-11-01
影响因子：
6
通讯作者：
Holmdahl, R
中科院分区：
文献类型：
--
作者：
Nandakumar, KS;Svensson, L;Holmdahl, R
转移H(CH)型胶原蛋白特异性单抗可诱导NAVE小鼠急性关节炎(H型胶原蛋白抗体诱导的关节炎，CAIA)。用一对分别与CH的J1和C1(I)表位结合的单抗M2139和CIIC1诱导小鼠关节炎。此后，通过注射脂多糖来增加该病的发病率和严重程度。该模型被用来研究基因、年龄、性别以及效应细胞在关节炎发病的终末期效应阶段的作用。注射单抗只在内毒素刺激后才能诱发关节炎。CAIA在不同敏感株之间的疾病穿透能力存在差异，表明非主要组织相容性复合体基因在抗体效应器途径中的重要性。B细胞缺陷小鼠易患CAIA，在某些遗传背景下，B细胞缺陷会导致关节炎加重。受影响的足掌组织学显示大量中性粒细胞渗入，伴随着骨和软骨的侵蚀、血管疙瘩形成和纤维蛋白沉积。中性粒细胞的耗尽显著降低了该病的发病率和严重程度。CAIA易感性随年龄增长而增加。男性比女性更容易患上关节炎，雌激素治疗可以减少关节炎的发展。我们得出结论，CAIA是一种由抗体结合和中性粒细胞绕过免疫激活而触发的急性关节炎，但与胶原性关节炎有许多共同特征。
Transfer of collagen type H (CH)-specific monoclonal antibodies induces an acute form of arthritis (collagen type H antibody-induced arthritis, CAIA) in nave mice. Arthritis was induced using a pair of monoclonal antibodies M2139 and CIIC1, binding to J1 and C1(I) epitopes of CH, respectively. Thereafter, lipopolysaccharide injection was used to increase the incidence and severity of the disease. This model was used to investigate the effect of genes, age, and sex as well as effector cells in the end-stage effector phase of arthritis pathogenesis. Injection of a single monoclonal antibody induced arthritis only after lipopolysaccharide stimulation. CAIA showed differences in disease penetration among the susceptible strains indicating the importance of non-major histocompatibility complex genes on the antibody effector pathway. B-cell-deficient mice were susceptible to CAIA and in some genetic backgrounds B-cell deficiency leads to enhanced arthritis. Histology of the affected paws revealed massive infiltrations of neutrophils along with bone and cartilage erosion, pannus formation, and fibrin deposition. Depletion of neutrophils significantly reduced the incidence and severity of the disease. CAIA susceptibility increased with age. Males were more susceptible than females and estrogen treatment decreased the development of arthritis. We conclude that CAIA is an acute arthritis triggered by antibody binding and neutrophils bypassing immune activation but with many characteristics in common with collagen-induced arthritis.