Review Article

Apoptosis and Autoimmunity

Autoimmunity in acute rheumatic fever (ARF) is triggered by group-A beta hemolytic streptococci (GAS). Although most of the recent work has focused on the major impact of lymphocytes, the exact immunopathogenesis is still unresolved. Regulation of self-tolerance in response to GAS has been investigated in various animal experiments. This study aimed to associate the ratio of lymphocytes bearing adhesion/costimulatory molecules, Bcl-2/CD95 and serum TGF-β1 concentrations with clinical stages of ARF. Thirty-five patients were assigned according to the clinical stages. Bcl-2 expression on CD19+ and CD3+ lymphocytes was similar within patient groups and controls. CD62p expression was higher in patients with carditis. The ratio of ICAM-1 bearing lymphocytes was significantly different between patient groups and controls and was increased through acute to remission stages longitudinally. In contrast, a gradual and significant decrease in TGF-β1 concentrations was observed longitudinally from acute to chronic stages. A positive correlation has been documented between ICAM-1+ lymphocyte ratios and Fas+ cytotoxic T cell ratios supported by a prominent increase in CD95+ T cells. These data draw our attention to the role of ICAM-1, Fas and TGF-β1 in ARF pathogenesis through the perspective of self-tolerance in a clinical setting.

The regulation of apoptotic cell death may have a profound effect on the pathogenesis and progression of colon cancer. Survivin, a member of the inhibitor of apoptosis gene family, has been detected in fetal tissue and in a variety of human malignancies. In the current study, we investigated survivin expression by an immunohistochemical approach in benign, hyperplastic, premalignant, and malignant lesions of the colon. Survivin was detected in all cases of normal colonic mucosa (20/20), hyperplastic polyps (20/20), adenomatous polyps (20/20), and in both well differentiated and moderately differentiated colonic adenocarcinomas (20/20). In the normal colonic mucosa, survivin expression was mostly restricted to the base of the colonic crypts. All epithelial cells showed uniformly intense staining for survivin in hyperplastic polyps. By contrast, adenomas and adenocarcinomas showed a heterogeneous staining pattern with cell-to-cell, gland-to-gland, and regional variability in the intensity of survivin staining. In contrast to the basal preponderance of staining in normal colonic mucosa, numerous survivin positive cells were present at the luminal surface of hyperplastic polyps, adenomatous polyps, and adenocarcinomas. In conclusion, the expression of survivin is not a specific marker of adenocarcinoma of the colon but does show characteristic and reproducible patterns of expression in non-neoplastic proliferative lesions and in normal colonic mucosa. HUM PATHOL 32:119-125. Copyright © 2001 by W.B. Saunders Company

To investigate the molecular mechanism of glandular parenchyma destruction in Sjögren's syndrome (SS), Bcl-2, Bax, Bcl-X, and Bak expression were studied. SS (n= 18) and control salivary glands (n= 6) were examined by immunohistochemistry. Apoptosis was assessed byin situDNA nick end labeling. Infiltrating mononuclear cells in the SS salivary gland showed elevated Bcl-2. These mononuclear cells expressed increased Bax but did not undergo apoptosis. Both SS and control salivary gland ductal epithelial cells expressed Bcl-2, Bax, and Bcl-X. SS, but not normal, salivary gland acinar cells expressed Bax and underwent apoptosis. These results suggest that elevated Bax expression in SS salivary gland acinar cells may play an important role in the apoptotic pathway. In contrast, Bcl-2 expression in SS infiltrating mononuclear cells and ductal cells may contribute to their survival.