The weakness in myasthenia gravis (MG) is mediated by T helper cell (Th)-dependent autoantibodies against neuromuscular epitopes. So far, analyzing Th phenotypes or antigen specificities has yielded very few clues to pathogenesis. Here we adopt an alternative antigen-independent approach, analyzing T cell receptor (TCR) Vb usage/ expansions in blood from 118 MG patients. We found major expansions (! five standard deviations above the mean of 118 healthy, individually age-and sex-matched controls) in diverse Vb in 21 patients (17.6%, p<0.001) among CD4 + T cells, and in 45 patients (38.1%, p<0.001) among CD8 + T cells. In informative probands, the expanded CD4+ cells consistently showed a Th cell phenotype (CD57 + CXCR5 + ) and expressed Th1 cytokines. Furthermore, their expression of markers for activation, lymphocyte trafficking and B cell-activating ability persisted for ! 3 years. Surprisingly, we noted a selective decline in the expansions/their CD57 positivity while the probands' MG was improving. CDR3 spectratyping suggested mono-or oligoclonal origins, which were confirmed by the prevalent TCR Vb CDR3 sequences of Th cells cloned from repeat bleeds. Thus, our data provide evidence for persistent clonally expanded CD4 + B helper T cell populations in the blood of MG patients. These unexpected CD4 + expansions might hold valuable clues to MG immunopathogenesis.

Total PTX with AT in pediatric patients with rHPT is a safe and effective procedure. It should be considered if rHPT is refractory to conservative treatment, in view of the risk of potentially lethal vascular calcifications developing in the majority of adults with childhood onset of CKD.