P-glycoprotein function in peripheral T lymphocyte subsets of myasthenia gravis patients: clinical implications and influence of glucocorticoid administration.
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with a chronic clinical course that requires long-term glucocorticoid (GC) therapy. A drug efflux pump, P-glycoprotein (P-gp), actively transports GC out of target cells, thereby reducing its efficacy. We evaluated the P-gp function of peripheral-blood mononuclear cells in 59 MG patients. P-gp function was estimated from a decrease in fluorescent P-gp substrate Rhodamine 123 and its inhibition by the conformation-sensitive UIC2 monoclonal antibody. P-gp function on CD8(+) T cells in 21 MG patients having experienced GC therapy was higher than that in 19 MG patients having no history of GC therapy (p=0.026). There was a significant correlation between P-gp function in CD3(+) (r=0.55, p=0.014) or CD4(+) (r=0.48, p=0.034) T cells and the total dose of prednisolone for treatment. P-gp function on CD4(+) T cells in MG patients who showed low responses to prednisolone therapy (n=8) was higher than that in patients who showed relatively high responses to prednisolone therapy (n=10) (p=0.045). These results suggest that higher P-glycoprotein activity on CD3(+) or CD4(+) cells necessitated treatment with higher steroid doses in order to achieve a clinical response. The measurement of P-gp function on CD4(+) T cells is useful in the assessment of clinical response to GC therapy.
Tanaka
Sachiko
S
Third Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. sachiko@ps.toyaku.ac.jp
Masuda
Masayuki
M
Nakajima
Kanako
K
Ido
Nobuhiro
N
Ohtsuka
Takao
T
Nishida
Masashi
M
Utsumi
Hiroya
H
Hirano
Toshihiko
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000188:drug therapy / Q000276:immunology* / Q000601:surgery; D011239:Prednisolone / Q000008:administration & dosage*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D013934:Thymectomy
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D011239:Prednisolone