Yoo J U, Kresina T F, Malemud C J, Goldberg V M
Proc Natl Acad Sci U S A. 1987 Feb;84(3):832-6. doi: 10.1073/pnas.84.3.832.
This study details the immune response to cartilage proteoglycan in experimental chronic IgG-induced immune synovitis. Antibodies reactive with purified rabbit proteoglycan monomer were observed in nine of nine rabbits with immune synovitis. IgG-immunized but nonsynovitic control animals with no pathology showed no antibody response. A panel of murine monoclonal antibodies with defined specificity towards rabbit proteoglycan were utilized to characterize the epitope specificity of the immune synovitis polyclonal anti-proteoglycan response. One murine monoclonal antibody, 6C11, inhibited the binding of the polyclonal antisera to proteoglycan in all nine animals with significant (greater than 40%) inhibition in six of nine rabbits. Further inhibition studies utilizing DEAE-cellulose-resolved proteoglycan tryptic peptides revealed that peptides poor in chondroitin sulfate were strong inhibitors of binding of the polyclonal antibodies to the proteoglycan substrate. In particular, keratan sulfate-containing tryptic peptides were most inhibitory on a per weight basis. These results indicate that, in chronic IgG-induced immune synovitis, anti-proteoglycan antibodies elicited are heterogeneous with regard to specificity, but a relatively large proportion predominantly recognized a portion of the proteoglycan molecule containing core protein and associated keratan sulfate.
本研究详细阐述了实验性慢性IgG诱导的免疫性滑膜炎中对软骨蛋白聚糖的免疫反应。在9只患有免疫性滑膜炎的兔子中，均观察到与纯化兔蛋白聚糖单体反应的抗体。接受IgG免疫但无病理变化的非滑膜炎对照动物未显示抗体反应。利用一组对兔蛋白聚糖具有明确特异性的鼠单克隆抗体来表征免疫性滑膜炎多克隆抗蛋白聚糖反应的表位特异性。一种鼠单克隆抗体6C11在所有9只动物中均抑制多克隆抗血清与蛋白聚糖的结合，其中9只兔子中有6只的抑制率显著（大于40%）。利用DEAE - 纤维素分离的蛋白聚糖胰蛋白酶肽进行的进一步抑制研究表明，硫酸软骨素含量低的肽是多克隆抗体与蛋白聚糖底物结合的强抑制剂。特别是，含硫酸角质素的胰蛋白酶肽按重量计算抑制作用最强。这些结果表明，在慢性IgG诱导的免疫性滑膜炎中，所引发的抗蛋白聚糖抗体在特异性方面具有异质性，但相对较大比例的抗体主要识别包含核心蛋白和相关硫酸角质素的蛋白聚糖分子部分。
