Pathogenetic significance of fetal-type acetylcholine receptors on thymic myoid cells in myasthenia gravis.
To investigate the role of thymic myoid cells in the pathogenesis of myasthenia gravis (MG), mRNA of nonneoplastic thymuses from eight MG patients was analyzed by dot blot hybridization for the occurrence of acetylcholine receptor (AChR) subunit transcripts, using the five AChR-subunit cDNAs (alpha, beta, gamma, delta, and epsilon) as probes. Attention was particularly paid to the gamma- and epsilon-subunit transcripts that specify fetal- or adult-type AChR. In all eight thymuses, transcripts of the alpha-, beta-, gamma-, and delta-subunit genes were detected. Relative autoradiographic signal intensities correlated with the frequencies of thymic myoid cells as determined by immunostaining with anti-AChR monoclonal antibodies. In only one of these thymuses were transcripts of the epsilon-subunit gene detected in addition to those of the other subunit genes. Four MG-associated thymomas without myoid cells were devoid of any AChR-subunit mRNA. Our findings imply that fetal-type AChR is expressed in MG thymuses as a rule, whereas adult-type AChR is coexpressed with it only in a minority of cases. A similar pattern of cotranscription is known to occur at certain stages of muscle development, and can be found in human rhabdomyosarcomas with an intermediate stage of myogenesis. Because the serum autoantibodies of MG patients exhibit preferential reactivity with fetal AChRs, the presence of fetal AChRs in the thymus provides circumstantial evidence for an active involvement of thymic myoid cells in the autoimmune process.
Geuder
K I
KI
Pathologisches Institut, Universität Würzburg, Germany.
Marx
A
A
Witzemann
V
V
Schalke
B
B
Toyka
K
K
Kirchner
T
T
Müller-Hermelink
H K
HK
D000911:Antibodies, Monoclonal; D004247:DNA / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D009157:Myasthenia Gravis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011950:Receptors, Cholinergic / Q000032:analysis* / Q000276:immunology; D013950:Thymus Gland / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D004247:DNA