Carlsen Stefan, Lu Shemin, Holmdahl Rikard
Medical Inflammation Research, Lund University, Sweden.
Methods Mol Med. 2007;136:225-42. doi: 10.1007/978-1-59745-402-5_17.
Type XI collagen (CXI) and cartilage oligomeric matrix protein (COMP) are minor components in cartilage, shown to be arthritogenic. CXI is a heterotrimeric triple helical fibrillar collagen and intermingled in the collagen fibers with type II (CII). COMP is the major noncollagenous protein of cartilage and is a homopentamer, interacting with the collagen fibers with each of its subunits. Similar to CII, homologous rat CXI also induces a chronic arthritis in rats but with a different major histocompatibility complex (MHC) genetic control and pathogenesis. CXI induced arthritis (C(XI)IA) is characterized by a more pronounced chronic relapsing disease course. The MHC allele of importance is the RT1f haplotype and, surprisingly, some of the CII associated MHC alleles like RT1a are less permissive. Immunization with COMP induces a severe but self-limited arthritis in strains with a genetic background resistant to most other forms of arthritis or even autoimmune models, the E3 rat. The MHC association also differs between the different models (CIA, CXI, and COMPIA). An autoimmune response to COMP is triggered despite the circulation of COMP fragments in both physiologic and arthritic states. The induction of arthritis in rats with CXI or COMP provides an arthritis models with a distinct pathogenesis as compared with other induced arthritis models.
XI型胶原蛋白(CXI)和软骨寡聚基质蛋白(COMP)是软骨中的次要成分,已被证明具有致关节炎作用。CXI是一种异源三聚体三螺旋纤维状胶原蛋白,与II型胶原蛋白(CII)混合存在于胶原纤维中。COMP是软骨的主要非胶原蛋白,是一种同五聚体,其每个亚基都与胶原纤维相互作用。与CII类似,同源大鼠CXI也会在大鼠中诱发慢性关节炎,但主要组织相容性复合体(MHC)的基因控制和发病机制不同。CXI诱导的关节炎(C(XI)IA)的特点是慢性复发性病程更为明显。重要的MHC等位基因是RT1f单倍型,令人惊讶的是,一些与CII相关的MHC等位基因,如RT1a,反而不太容易引发疾病。用COMP免疫可在对大多数其他形式的关节炎甚至自身免疫模型具有遗传抗性的品系(E3大鼠)中诱发严重但自限性的关节炎。不同模型(CIA、CXI和COMPIA)之间的MHC关联也有所不同。尽管COMP片段在生理状态和关节炎状态下都会循环,但仍会引发针对COMP的自身免疫反应。与其他诱导性关节炎模型相比,用CXI或COMP诱导大鼠患关节炎可提供具有独特发病机制的关节炎模型。