Tissue concentrations of gastrointestinal regulatory peptides in the duodenal mucosa in systemic sclerosis

Objective Esophageal hypomotility and abnormalities of intestinal function are important manifestations in systemic sclerosis (SSc), but their pathogenesis is not well understood. Since there is evidence that plasma concentrations of certain gastrointestinal regulatory peptides are increased in SSc, we were interested in examining the peptide concentrations and localization in biopsy specimens from the intestinal mucosa in SSc patients. We studied 12 patients with gastrointestinal disease. Methods Levels of corticotrophin-releasing hormone (CRH), motilin, neuropeptide Y (NPY) and peptide YY (PYY) were determined by radioimmunoassay and high-performance liquid chromatography (HPLC), and the occurrence of motilin, PYY, somatostatin, and NPY were studied with immunohistochemistry. Results Except for the concentrations of CRH, which were increased 2-fold, the tissue concentration of motilin, NPY and PYY were decreased by approximately 50% among patients with esophageal and intestinal dysfunction (group B) compared to patients with impaired esophageal motility alone (group A). In addition, HPLC-characterization of motilin, NPY, and PYY showed a different pattern of fragments among patients in groups A and B. In all patients duodenal motilin, PYY, and somatostatin were localized in the endocrine cells. The distribution and frequency of the cells did not differ among the patients. NPY was localized to neuronal elements; there was no overt difference among the patients with respect to the frequency of NPY-containing nerves. Conclusion This study shows that patients with widespread gastrointestinal disease have lower tissue concentrations of regulatory peptides compared to patients with less widespread disease.