The immunologic role of thymectomy in the treatment of myasthenia gravis: implication of thymus-associated B-lymphocyte subset in reduction of the anti-acetylcholine receptor antibody titer.
OBJECTIVE
Thymectomy is generally accepted as the major option of treatment for myasthenia gravis. To elucidate the biological role of thymectomy in the treatment of myasthenia gravis, the immunologic characteristics of the thymus was studied in association with the postoperative kinetics of the anti-acetylcholine receptor antibody titer.


METHODS
Thirty-four patients with nonthymomatous myasthenia gravis who had positive anti-acetylcholine receptor antibody titer and undergoing extended thymectomy were subjected to the study. Reduction of anti-acetylcholine receptor antibody titer was evaluated in terms of the proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy to that before the operation. The numbers of B lymphocytes (CD19(+) cells) and the germinal center B lymphocytes (CD19(+)CD38(high) cells) present in 1 g of the thymic tissue were calculated by flow cytometry.


RESULTS
The proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy ranged from 27.5% to 150%. The numbers of B lymphocytes and the germinal center B lymphocytes in 1 g of the thymic tissue ranged from 0.19 x 10(6)/g to 162.8 x 10(6)/g and from 0.09 x 10(6)/g to 33.4 x 10(6)/g, respectively. The proportion of anti-acetylcholine receptor antibody titer at 1 year after thymectomy had a significant inverted correlation with the number of B lymphocytes (P =.002) as well as that of the germinal center B lymphocytes (P =.007).


CONCLUSIONS
Effectiveness of thymectomy was dependent on predominance of B lymphocytes and the germinal center B lymphocytes in the thymus, suggesting that one of the biological roles of thymectomy in the treatment of myasthenia gravis is removing the thymus-associated germinal centers.
Okumura
Meinoshin
M
Department of Surgery, Osaka University Graduate School of Medicine, Japan. m-okumura@kch.hosp.go.jp
Ohta
Mitsunori
M
Takeuchi
Yukiyasu
Y
Shiono
Hiroyuki
H
Inoue
Masayoshi
M
Fukuhara
Kenjiro
K
Kadota
Yoshihisa
Y
Miyoshi
Shinichiro
S
Fujii
Yoshitaka
Y
Matsuda
Hikaru
H
D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000032:analysis; D018941:Antigens, CD19 / Q000032:analysis; D001323:Autoantibodies / Q000097:blood*; D016175:B-Lymphocyte Subsets; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D011950:Receptors, Cholinergic / Q000276:immunology*; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology; D016896:Treatment Outcome
D015703:Antigens, CD; D018941:Antigens, CD19; D001323:Autoantibodies; D008562:Membrane Glycoproteins; D011950:Receptors, Cholinergic; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1