We have previously reported alterations of the thymus in

We have previously reported alterations of the thymus in AChR-MG patients, especially in their germinal center PHA-848125 (defined as CD19+CD38+ cells by flow cytometric analysis). First, we found that, in MG thymi, this subset failed to show the normal down-regulation of Bcl-2, suggesting that autoreactive B cells that normally undergo apoptosis in germinal centers may aberrantly survive in MG (Shiono et al., 1997). We then reported that reductions in anti-AChR antibody titers 1 year after thymectomy correlated significantly with the number of thymic CD19+ and CD19+CD38+ cells (Okumura et al., 2003). Those findings suggested that one of the biological roles of thymectomy as treatment for MG is removing thymic germinal centers and interruption of the concomitant antibody diversification. The advantage of this type of flow cytometric analysis is that it examines the entire thymus (regardless of any fatty replacement and surrounding fat tissues). In the present study, histological findings and germinal center numbers varied among the SN-MG patients, so the average values were lower than in the AChR-MG patients. However, several of the SN-MG patients (e.g. patient 2) showed thymic hyperplasia strikingly similar to that in AChR-MG, whereas others showed atrophy. In addition, Bcl-2 protein in thymic CD19+CD38+ cells from 2 SN-MG patients was as highly expressed as in AChR-MG thymi. We propose that autoreactive B cells in these patients' thymi may have escaped the negative selection normally seen in the germinal centers in secondary lymphoid follicles in tonsils. We show here that several SN-MG patients had very similar thymic hyperplasia to that in AChR-MG; it apparently correlated with improvements in their MG after thymectomy, but that demands confirmation in a larger series. By contrast, hyperplasia was much less obvious in MuSK-MG, where the thymus was usually normal or atrophic (Evoli et al., 2003). Presently, surgery is considered unsuitable for the treatment of MuSK-MG, where the thymus shows few abnormalities (Lauriola et al., 2005, Leite et al., 2005). By contrast, if the thymus is hyperplastic in SN-MG (as in patient 2), its removal may be beneficial. Although further studies are required, physicians and surgeons should be aware that this subgroup includes individuals who may benefit.
Acknowledgments