Identification of correlations between numbers of CD4+ CD25+ Treg cells, levels of sera anti-AChR antibodies and transfer growth factor-beta in patients with myasthenia gravis

OBJECTIVE: The purpose of the current study is to demonstrate possible involvement of CD4+ CD25+ Treg cells and TGF-beta in immune activation in patients with myasthenia gravis (MG). If so, how does CD4+ CD25+ Treg cells and TGF-beta, collaborate to impact on the production of pathogenic anti-AChR antibodies (Ab)? METHODS: 40 MG in-patients with recent onset or deterioration and age and gender-matched 38 healthy subjects were consecutively enrolled. Flow cytometry was employed to detect circulating CD4+ CD25+ Treg cells. Levels of AChR-Abs and TGF-beta1 in serum were detected by radioimmunoassay and enzyme-linked immunoabsorbance assay respectively. RESULTS: Numbers of CD4+ CD25+ Treg cells were significantly decreased in MG patients (3.0% +/- 2.5%) compared with healthy controls(4.6% +/- 3.7% , P = 0.03). Decreased production of CD4+ CD25+ Treg cells was associated with late-onset, longer-duration, positive-MG sera for AChR-Abs, normal or atrophic thymus, and non-thymectomy treatment et al, respectively. Although CD4+ CD25+ Treg cells were not linear-correlated with serum anti-AChR Ab titers, but were conversely correlated with each other in MG patients without thymoma (non-MGT) (r = -0.37, P = 0.02). Likewise, levels of TGF-beta1 in 31 non-MGT patients (112 ng/L +/- 83 ng/L) were decreased compared with those of healthy subjects (215 ng/L +/- 134 ng/L, P = 0.00), and was conversely correlated with titers of anti-AChR Abs (r = -0.37, P = 0.02). The titer of anti-AChR Abs were correlated with Osserman classification and MGFA grade (r = 0.34, P = 0.03). CONCLUSION: Numbers of CD4+ CD25+ Treg cells and levels of TGF-beta1 in MG patients were significantly decreased compared with healthy controls, and may thus contribute to the pathogenesis of MG. Numbers of CD4+ CD25+ Treg cells were conversely correlated with levels of anti-AChR Abs in non-MGT patients.