Corrales J J, Orfao A, López A, Ciudad J, Mories M T
Servicios de Endocrinología, Universidad de Salamanca, Spain.
J Endocrinol. 1996 Nov;151(2):231-40. doi: 10.1677/joe.0.1510231.
The immunosuppressive effects of antithyroid drug therapy are well recognized; however, the cellular mechanisms underlying their action remain largely unknown. In the present paper we have prospectively analyzed the in vivo effects of methimazole treatment on a large number of circulating B cell subsets, involved in the effector phase of the immune response, in a group of 18 hyperthyroid patients with Graves' disease (GD). The patients were sequentially studied before (day 0) and 7, 14, 30, 90 and 180 days after methimazole therapy. The results were compared with both a group of 19 age- and sex-matched healthy controls and a group of 20 untreated/euthyroid GD patients in long-term remission. The combination of flow cytometry and three colour immunofluorescence revealed a clear increase (P < 0.001) in the numbers of circulating total B cells (CD19+) due to a significant increase (P < 0.001) in the CD5+, FMC7+, CD5+/ FMC7+ and CD23+ B cell subsets in hyperthyroid GD patients with respect to both healthy individuals and to GD patients in long-term remission. The absolute numbers of all these B cell subsets analyzed before treatment, although abnormal, were not statistically different from those observed during the whole period of therapy. When comparing the percentages of these B cell subsets during treatment, significant changes (P < 0.001) were only observed in the proportion of CD5+, CD5+/FMC7+ and CD5- B cells at the end of the follow-up period with respect to those found both before and during the first month of therapy. Whereas CD5+ and CD5+/FMC7+ B cells decreased (P < 0.001) after 3 months of therapy, CD5- B cells showed a significant increase (P < 0.001) at the end of therapy. It is remarkable that the percentage of CD5+, CD5+/FMC7+, CD5- and CD23+ B cell subsets were abnormal during the whole period of treatment and that they never reached normal values. These results show that, in vivo, GD patients treated with methimazole exhibited an abnormal but rather stable pattern of B cell distribution, similar to that present in hyperthyroid untreated GD patients, except for the CD5+ and CD5- B cell populations. Our findings suggest that in vivo methimazole therapy would not directly have an important influence on circulating B cell subsets.
抗甲状腺药物治疗的免疫抑制作用已得到充分认识；然而，其作用的细胞机制在很大程度上仍不清楚。在本文中，我们前瞻性地分析了甲巯咪唑治疗对一组18例格雷夫斯病（GD）甲亢患者体内大量参与免疫反应效应阶段的循环B细胞亚群的影响。在甲巯咪唑治疗前（第0天）以及治疗后7、14、30、90和180天对患者进行了连续研究。将结果与一组19例年龄和性别匹配的健康对照以及一组20例未经治疗/甲状腺功能正常且长期缓解的GD患者进行了比较。流式细胞术和三色免疫荧光相结合的方法显示，甲亢GD患者循环总B细胞（CD19+）数量明显增加（P < 0.001），这是由于CD5+、FMC7+、CD5+/FMC7+和CD23+B细胞亚群数量显著增加（P < 0.001），与健康个体和长期缓解的GD患者相比均如此。治疗前分析的所有这些B细胞亚群的绝对数量虽然异常，但与治疗全过程中观察到的数量无统计学差异。在比较治疗期间这些B细胞亚群的百分比时，仅在随访期末观察到CD5+、CD5+/FMC7+和CD5 - B细胞比例相对于治疗前和治疗第一个月期间有显著变化（P < 0.001）。治疗3个月后，CD5+和CD5+/FMC7+B细胞减少（P < 0.001），而CD5 - B细胞在治疗结束时显著增加（P < 0.001）。值得注意的是，CD5+、CD5+/FMC7+、CD5 - 和CD23+B细胞亚群的百分比在整个治疗期间均异常，且从未达到正常水平。这些结果表明，在体内，接受甲巯咪唑治疗的GD患者表现出异常但相当稳定的B细胞分布模式，类似于未经治疗的甲亢GD患者，除了CD5+和CD5 - B细胞群体。我们的研究结果表明，在体内甲巯咪唑治疗不会直接对循环B细胞亚群产生重要影响。
