FK506 attenuates thymic output in patients with myasthenia gravis.
BACKGROUND
Myasthenia gravis (MG) is an antibody-mediated, T-cell-dependent autoimmune disease. The symptoms are caused by high-affinity IgG against the muscle acetylcholine receptor (AChR) at the neuromuscular junction. The production of these antibodies in B-cells depends on AChR-specific CD4(+) T-cells and the thymus gland seems to play a significant role in the pathogenesis of MG. Altered thymic T-cell export seems to be associated with a pathological mechanism in myasthenia gravis. Tacrolimus (FK506) has recently been used to treat MG.


METHODS
We examined the effects of tacrolimus on thymic T-cell export in patients with MG. Sixteen patients with nonthymomatous and/or thymectomized MG were treated with oral administrations of tacrolimus. To assess the effect of tacrolimus on the thymic output, we assayed the levels of T-cell receptor excision circle (TREC), a molecular marker of thymus emigrants.


RESULTS
T-cell receptor excision circle was not significantly different from those in age-matched controls before tacrolimus therapy, but they were partially decreased 4 months after tacrolimus therapy. T-cell receptor excision circle levels were significantly decreased in the thymomatous group (p < 0.05), but not in the nonthymomatous group. Tacrolimus treatment significantly attenuated TREC levels in cultured CD4(-)CD8(+) cells (p < 0.05), but total cell counts were not significantly changed.


CONCLUSIONS
These results indicate that TREC levels may become a marker of the curative effect of tacrolimus therapy for thymomatous MG, and that tacrolimus suppresses not only activating T-lymphocytes, but also naïve T-cells.
Tokushima National Hospital, National Hospital Organization, Tokushima, Japan ; Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Takao
T
Mitsui
Tokushima National Hospital, National Hospital Organization, Tokushima, Japan ; Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Yukiko
Y
Kuroda
Department of Psychiatry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Shu-Ichi
S
Ueno
Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Naoko
N
Matsui
Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Ryuji
R
Kaji
T cell receptor excision circle; T-cell receptor excision circle; cell culture; lymphocytes