Parekh R B, Dwek R A, Sutton B J, Fernandes D L, Leung A, Stanworth D, Rademacher T W, Mizuochi T, Taniguchi T, Matsuta K
Nature. 1985;316(6027):452-7. doi: 10.1038/316452a0.
Rheumatoid arthritis (RA) is a widely prevalent (1-3%) chronic systemic disease thought to have an autoimmune component; both humoral and cellular mechanisms have been implicated. Primary osteoarthritis (OA) is considered to be distinct from rheumatoid arthritis, and here damage is thought to be secondary to cartilage degeneration. In rheumatoid arthritis, immune complexes are present that consist exclusively of immunoglobulin, implying that this is both the 'antibody' (rheumatoid factor [RF]) and the 'antigen' (most commonly IgG). Autoantigenic reactivity has been localized to the constant-region (C gamma 2) domains of IgG. There is no evidence for a polypeptide determinant but carbohydrate changes have been reported. We have therefore conducted a study, simultaneously in Oxford and Tokyo, to compare in detail the N-glycosylation pattern of serum IgG (Fig. 1) isolated from normal individuals and from patients with either primary osteoarthritis or rheumatoid arthritis. The results, which required an evaluation of the primary sequences of approximately 1,400 oligosaccharides from 46 IgG samples, indicate that: (1) IgG isolated from normal individuals, patients with RA and patients with OA contains different distributions of asparagine-linked bi-antennary complex-type oligosaccharide structures, (2) in neither disease is the IgG associated with novel oligosaccharide structures, but the observed differences are due to changes in the relative extent of galactosylation compared with normal individuals. This change results in a 'shift' in the population of IgG molecules towards those carrying complex oligosaccharides, one or both of whose arms terminate in N-acetylglucosamine. These two arthritides may therefore be glycosylation diseases, reflecting changes in the intracellular processing, or post-secretory degradation of N-linked oligosaccharides.
类风湿关节炎（RA）是一种广泛流行（1 - 3%）的慢性全身性疾病，被认为具有自身免疫成分；体液和细胞机制均与之相关。原发性骨关节炎（OA）被认为与类风湿关节炎不同，其损伤被认为是软骨退变的继发结果。在类风湿关节炎中，存在仅由免疫球蛋白组成的免疫复合物，这意味着它既是“抗体”（类风湿因子[RF]）又是“抗原”（最常见的是IgG）。自身抗原反应性已定位到IgG的恒定区（Cγ2）结构域。没有证据表明存在多肽决定簇，但已报道有碳水化合物变化。因此，我们在牛津和东京同时开展了一项研究，以详细比较从正常个体以及原发性骨关节炎或类风湿关节炎患者中分离出的血清IgG的N - 糖基化模式（图1）。结果需要对46个IgG样本中约1400个寡糖的一级序列进行评估，结果表明：（1）从正常个体、类风湿关节炎患者和骨关节炎患者中分离出的IgG含有不同分布的天冬酰胺连接的双触角复合型寡糖结构；（2）在这两种疾病中，IgG均未与新的寡糖结构相关联，但观察到的差异是由于与正常个体相比半乳糖基化相对程度的变化。这种变化导致IgG分子群体向携带复合型寡糖的分子“转移”，其中一个或两个臂以N - 乙酰葡糖胺终止。因此，这两种关节炎可能是糖基化疾病，反映了N - 连接寡糖的细胞内加工或分泌后降解的变化。
