Expression of apoptotic and proliferation factors in gastric mucosa of patients with systemic sclerosis correlates with form of the disease.

ABSTRACT

Despite high prevalence of patients with gastric disease in systemic sclerosis (SSc), its pathogenesis is still poorly understood. We immunohistochemically analysed biopsies of gastric mucosa (GM) in 5 controls and 15 patients with different forms of SSc limited cutaneous (lc), diffuse cutaneous moderate (sys1) and severe (sys2). The number of positive cells was analysed by a Kruskall-Wallis test, P < 0.05 was considered statistically significant. Percentage of proliferating (Ki-67 positive) cells was highest in sys1 (3% in superficial and 4,6% in deeper parts of GM), which dropped to 1% in sys2. Percentage of α-smooth muscle actin (α-SMA) positive cells was 5% in controls, 9% in superficial GM, while in deeper GM rose from 7% to 19% in sys1 and sys2, thus indicating increased myofibroblast population. Caspase-3 positive apoptotic cells characterized 1,5-2% of controls, 8% of superficial and 6% of deeper GM cells in sys1. In sys2, apoptosis affected 50% of surface epithelial and gland cells and 30% of deeper glands, and correlated with increased fibrosis and decreased syndecan-1 expression. Our data demonstrate that sys1 is the most "active" proliferating form of SSc. Sys2 characterize collagen deposition, surface epithelium defects, extensive apoptosis and low proliferation, GM atrophy and loss of function.