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Factor XIIIa, a circulating form of transglutaminase, plays a key role in intestinal mucosal repair. We found that transglutaminase levels are decreased in serum of patients with inflammatory bowel diseases and demonstrated in a rat model of chronic colitis that serum transglutaminase is closely related to the severity of intestinal damage. We aimed, therefore, to correlate serum transglutaminase levels with standard endoscopic and histopathologic grading systems in patients affected by ulcerative colitis (UC). In 249 patients with UC, we assayed serum transglutaminase activity by a radioenzymatic method and measured clinical activity index (CAI) according to modified Rachmilewitz's criteria. In a subset of 82 patients undergoing colonoscopy, endoscopic and histologic indices were studied. Biopsy specimens were also taken from 28 patients to measure myeloperoxidase (MPO) as a marker of mucosa inflammation. Serum transglutaminase levels significantly correlated with the CAI scoring (r = -0.63; P < 0.01); likewise serum transglutaminase showed the best correlation with endoscopic (r = -0.71; P < 0.001) and histologic (r = -0.79; P < 0.001) scores. Myeloperoxidase activity was significantly higher in patients with active UC than those in remission (P < 0.01), showing a significant correlation with serum transglutaminase levels (r = -0.68; P < 0.01). Immunohistochemistry showed factor XIIIa localization in the extracellular matrix of damaged mucosa. In conclusion, these results suggest that transglutaminase assay can be useful in managing UC as a serological, noninvasive indicator of intestinal mucosal status. [ABSTRACT FROM AUTHOR]

Factor XIII (FXIII) is the plasma-borne transglutaminase involved in fibrin clot stabilization and wound healing. FXIII levels in the plasma of patients with inflammatory bowel diseases are lower than normal and there is a significant inverse correlation of FXIII levels with clinical severity. Moreover, uncontrolled studies report beneficial effects of FXIII supplementation in patients resistant to conventional therapies. We investigated the effects of intravenous recombinant FXIII (rFXIII) treatment in experimentally induced rat colitis to verify that FXIII was the active agent in plasma FXIII concentrates and to better understand the potential therapeutic use of this protein. Colitis was induced by instillation of 12% 2.4,6-trinitrobenzenesulfonic acid (TNBS) in 50% ethanol into the colon of male Wistar rats. Rats were treated with 0.65 mg/kg rFXIII or vehicle (intravenously) daily for 10 days. Treatment was started either immediately after TNBS/EtOH instillation (to evaluate effects on developing lesions) or seven days later (to evaluate effects on established lesions). In both cases rats were killed either immediately after the end of treatment (to evaluate immediate effects) or 17 days later (to evaluate long-lasting effects). The effects of rFXIII were compared to positive (5-amino-2-hydroxybenzoic acid) control over a 35-day time course. The severity of lesions was determined by colon weight and macroscopic and histologic scores. Transglutaminase activity was measured in both colon tissue and serum. rFXIII treatment reduced lesion severity significantly not only in developing but also in established lesions. Improvements in healing persisted at least 18 days after treatment was discontinued. Serum and tissue transglutaminase levels were restored by rFXIII treatment. In conclusion, pure rFXIII is as effective as plasma FXIII concentrates in a rat model of experimental colitis. In addition, rFXIII significantly improves the healing of preexisting lesions, a characteristic useful in treatment of human inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to the article "Factor XIII Subunits in Relation to Same Others Hemostatic Parameters in Ulcerative Colitis," by Anthony Stadnicki, J. KJoczko, A. Nowak and colleagues in a 1991 issue of the "American Journal of Gastroenterology."