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FRI0481 Increased Caspase-3 Activity in the Stomach Tissue Correlates with Disease Activity and Severity in Systemic Sclerosis Patients – A Pilot Study
  1. M. Radić1,
  2. K. Borić1,
  3. S. Mardešić2,
  4. I. Tadin3,
  5. D. Martinović Kaliterna1
  1. 1Division of Rheumatology and Clinical Immunology, University Hospital Centre Split, University of Split School of Medicine
  2. 2Department of Histology and Embryology, University of Split Medical School
  3. 3Division of Gastroenterology, University Hospital Centre Split, University of Split School of Medicine, Split, Croatia

Abstract

Background Systemic sclerosis (SSc) is an autoimmune disease characterized by chronic inflammation, vascular injury and excessive fibrosis. Apoptosis is a key mechanism involved in all the stages of the disease: vascular damage, immune dysfunction, and fibrosis. Caspases are a family of endoproteases that provide critical links in cell regulatory networks controlling inflammation and cell death. Dysregulation of caspases underlies human diseases including cancer and inflammatory disorders, and major efforts to design better therapies for these diseases seek to understand how these enzymes work and how they can be controlled.

Objectives This pilot study aimed to explore the expression of caspase-3 in stomach tissue in SSc patients and possible correlation with disease activity and severity.

Methods A total of thirteen stomach tissue biopsies (11 SSc and 2 controls) were collected. The same investigator, blind to clinical features, performed upper gastrointestinal endoscopy. The sections of stomach tissue were separately incubated for 45 min with rabbit anti-human/mouse active caspase-3 primary antibody. The intensity of apoptosis according to the caspase 3 activity was semiquantitatively selected into four categories: mild, moderate and abundant. We evaluated the disease activity and severity using clinical and laboratory parameters according to a modified Medsger severity scale and activity score. The disease activity was assessed according to Valentini's Scleroderma Disease Activity Index. In all the patients skin involvement was assessed by the modified Rodnan skin score (mRSS). The study was approved by the University Hospital Split Ethics Committee.

Results Eleven SSc female patients [mean age 54.3 (13.6) years, median disease duration 13 years with minimum–maximum range 1–35 years] were enrolled in this study after they gave written informed consent. All patients fulfilled the ACR criteria for the diagnosis of SSc. Five SSc patients had moderate/abundant and six had mild apoptosis on the basis of the caspase 3 activity. In SSc patients, the number of apoptotic cells is high, and their distribution is observed in several layers of the stomach wall, including blood vessels (Figure 1). The skin involvement and disease duration were highly different between SSc patients regarding to the apoptosis level (P<0.05, P<0.05, Mann–Whitney test). No significant difference was found for autoantibody profile between SSc patients regarding apoptosis levels of stomach tissue. Disease activity and severity were higher in SSc patients with moderate/abundant apoptosis of the stomach tissue (P<0.05, P<0.05, Mann-Whitney test).

Figure 1.

Normal mucosa of the stomach: columnar surface epithelium (e), connective tissue lamina propria (lp), glands (g) (A); brown-staining nuclei and nuclear fragments of caspase-3 positive apoptotic cells in the lamina propria. Immunohistochemical staining to caspase-3 (B); part of lymphocyte accumulation and blood vessel (bv), both contacting numerous apoptotic cells (arrows) (C).

Conclusions In SSc patients we have showed increased caspase-3 activity (cell death) in the stomach tissue. Increased cell death in the stomach tissue correlates with disease duration, activity, severity and skin involvement.

Disclosure of Interest None declared

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