Rook G, Thompson S, Buckley M, Elson C, Brealey R, Lambert C, White T, Rademacher T
Department of Medical Microbiology, University College, Middlesex School of Medicine, London.
Eur J Immunol. 1991 Apr;21(4):1027-32. doi: 10.1002/eji.1830210425.
The proportion of agalactosyl IgG [Gal(O)] is raised in human rheumatoid arthritis and tuberculosis. We report here that injection of pristane into the peritoneal cavities of mice on days 0 and 50, which is known to induce plasmacytomas and arthritis, also induced a rise in the proportion of Gal(O), correlating with a simultaneous rise in the level of IgG antibody binding to the 65-kDa heat-shock protein of Mycobacterium bovis (hsp65). Arthritis developed in a proportion of those CBA/Igb mice with the highest percentage of Gal(O). Pretreatment with 50 micrograms of recombinant mycobacterial hsp65 intraperitoneal (i.p.) on day -10, or with 500 rad irradiation on day -2 before the first of the two injections of pristane reduced the incidence of arthritis from 24% in control animals, to 5.3% and 0.4%, respectively. The reduced incidence of disease correlated with smaller rises in the % Gal(O) at 50-75 days, although levels at 150-200 days were not affected. The arthritogenic effect of oil was not confined to the pristane model, since a single i.p. injection of oil 21 days before immunizing DBA/1 mice with type II collagen reduced the mean day of onset of this arthritis, [which we have previously shown to correlate with raised % Gal(O)], from 38 to 15 days (p less than 0.001). One interpretation is that an autoimmunogenic stimulus, given when % Gal(O) is raised, is more likely to evoke disease. Since oil granulomata are known to secrete interleukin 6, which has B cell-regulatory properties and is secreted by rheumatoid synovial cells, we tested sera from interleukin 6-transgenic mice, and found a strikingly raised percentage of Gal(O). We suggest, therefore, that the role of oil in the induction of arthritis is the dysregulation of cytokine release of which a raised percentage of Gal(O) may be a direct or indirect consequence, associated with an increased susceptibility to autoimmunogenic stimuli.
无半乳糖基IgG[Gal(O)]在人类类风湿性关节炎和结核病中所占比例升高。我们在此报告，在第0天和第50天向小鼠腹腔注射已知可诱导浆细胞瘤和关节炎的 pristane，也会导致Gal(O)比例升高，这与同时升高的与牛分枝杆菌65 kDa热休克蛋白（hsp65）结合的IgG抗体水平相关。在那些Gal(O)百分比最高的CBA/Igb小鼠中，有一定比例的小鼠发生了关节炎。在第-10天腹腔注射50微克重组分枝杆菌hsp65，或在两次注射pristane中的第一次之前第-2天进行500拉德照射，可将关节炎的发生率从对照动物的24%分别降至5.3%和0.4%。疾病发生率的降低与50 - 75天时Gal(O)%的较小升高相关，尽管150 - 200天时的水平未受影响。油的致关节炎作用并不局限于pristane模型，因为在用II型胶原免疫DBA/1小鼠前21天单次腹腔注射油，可将这种关节炎的平均发病天数[我们之前已表明其与升高的Gal(O)%相关]从38天降至15天（p<0.001）。一种解释是，当Gal(O)%升高时给予的自身免疫原性刺激更有可能引发疾病。由于已知油肉芽肿会分泌具有B细胞调节特性且由类风湿滑膜细胞分泌的白细胞介素6，我们检测了白细胞介素6转基因小鼠的血清，发现Gal(O)的百分比显著升高。因此，我们认为油在关节炎诱导中的作用是细胞因子释放失调，Gal(O)百分比升高可能是其直接或间接后果，这与对自身免疫原性刺激的易感性增加有关。
