SERIAL ANALYSIS OF THE EFFECTS OF METHIMAZOLE THERAPY ON CIRCULATING B-CELL SUBSETS IN GRAVES-DISEASE

The immunosuppressive effects of antithyroid drug therapy are well rec ognized; however, the cellular mechanisms underlying their action rema in largely unknown. In the present paper we have prospectively analyze d the in viva effects of methimazole treatment on a large number of ci rculating 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 comp ared 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 tot al 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 patien ts with respect to both healthy individuals and to GD patients in long -term remission. The absolute numbers of all these B cell subsets anal yzed before treatment, although abnormal, were not statistically diffe rent from those observed during the whole period of therapy. When comp aring the percentages of these B cell subsets during treatment, signif icant 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 r espect to those found both before and during the first month of therap y. Whereas CD5+ and CD5+/FMC7+ B cells decreased (P<0.001) after 3 mon ths 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+, C D5+/FMC7+, CD5 - and CD23+ B cell subsets were abnormal during the who le period of treatment and that they never reached normal values. Thes e results show that, in vivo, GD patients treated with methimazole exh ibited an abnormal but rather stable pattern of B cell distribution, s imilar to that present in hyperthyroid untreated GD patients, except f or the CD5+ and CD5 - B cell populations. Our findings suggest that in vivo methimazole therapy would not directly have an important influen ce on circulating B cell subsets.