**3. Discussion**

Histopathological features of the esophagus in SSc and MCTD patients are similar, but muscular change in SSc is more progressive than in MCTD patients in our study. It has been suggested that there is no association between manometric abnormality and cutaneous symptoms in MCTD patients, and the characteristics of SSc are not always linked to esophageal dysfunction [5]. The pathological mechanism of esophageal dysfunction in MCTD may be similar but not always identical to that in SSc.

In patients with CTDs, autoimmune inflammation occurs in systemic organs such as kidney, lung, skin and blood vessels, and so on. The gastrointestinal tract is also involved though the histological features and grades are different from disease to disease even in the same CTD.

In CTDs, many kinds of autoantibodies may play an important role in causing the various symptoms and diseases, whether they are fatal or not. These differ from disease to disease and from tissue to tissue. We showed that IgG from MCTD patients reacts to various tissues such as kidney and lung (unpublished data) (Figure 7). It is well known that pulmonary hyperten‐ sion is the fatal cause of MCTD. Anti-endothelial cell antibody (AECA) was identified in the serum of MCTD patients, and was especially high in patients with pulmonary hypertension [21]. We now examine the antigen of AECA in endothelial cells of small pulmonary vascular vessels [22]. As for the autoantibody of MCTD against esophagus, our study revealed that IgG extracted from MCTD patients showed a positive immunohistochemical reaction not only for the smooth muscle cells of esophagus, but also for the ganglion cells in Auerbach's plexus, the vascular walls in esophageal muscular tissues, and squamous epithelium of the esophagus. Dysphagia in MCTD and SSc patients may be one of the symptoms often occurring as an autoimmune reaction.

The reason why the inner layer of the lower portion incurs more severe damage than other portions has not been clarified. Esophageal manometry shows that this portion sustains more intense mechanical stress in peristalsis than the outer layer or upper portions. Thus autoanti‐ bodies, mechanical stress and regurgitation may induce the severe dysphagia in MCTD and other CTDs.

Motility dysfunction is not a direct cause of death, but a strong association between esophageal dysmotility and interstitial lung disease in patients with MCTD is indicated [23]. Therefore, care must be taken with diagnosis.

**Figure 7.** Reaction of IgG from MCTD patients with various tissues. (A) kidney, (B) lung
