Elevated plasma cryofibrinogen in patients with active inflammatory bowel disease is morbigenous

Abstract

Aim: To investigate the role of cryofibrinogen (CF) in active inflammatory bowel disease (IBD).

Methods: CF was assayed in 284 subjects: 61 with active and 63 with inactive ulcerative colitis (UC), 45 who had proctocolectomy, 35 with active and 20 with inactive Crohn's disease (CD), 40 with other diseases and 20 healthy controls. Trypsin inhibitor (TI) and TI antibody (TI-Ab) were measured in plasma and CF complex by ELISA.

Results: CF in active UC was strikingly high compared with all other groups (c2<0.001). Similarly, CF was significantly higher in active CD than in inactive CD or in controls (c2<0.01). In UC, high CF and TI-Ab were associated with the need for operations. Further, high CF, CF/fibrinogen ratio, low TI and high TI-Ab in plasma were associated with disease activity or refractoriness to medication. Elevated CF was not associated with acute reactants like C-reactive protein and white blood cell counts except for erythrocyte sedimentation rate, suggesting that elevated CF was not a consequence of acute inflammation.

Conclusion: Elevated CF in active IBD appears to be morbigenous. CF promotes IBD via two main mechanisms, quenching of TI (an anti-inflammatory substance) and impairing microvascular perfusion by forming protein aggregates. CF may also serve as a biomarker of chronic IBD. Additional studies are warranted to fully evaluate the role of CF in IBD and the outcome should contribute to a better understanding of the pathogenesis of IBD.

Figure 1

Cryofibrinogen (CF) concentration in subgroups of 284 patients. ^bP<0.001 for active UC vs healthy control or UC post OP, inactive CD, acute colitis, and other disease control; ^dP< 0.01 for inactive UC and active CD vs healthy control, UC post OP, inactive CD, acute colitis, and other disease control; ^aP<0.05 for collagen disease vs healthy control or UC post OP, inactive CD, acute colitis; ^cP<0.05 for active UC vs inactive UC and active CD; ^eP<0.05 for UC post OP, inactive CD, acute colitis, and other disease control vs healthy control.

Figure 2

Simple regression analysis for relationship between plasma CF concentration and erythrocyte sedimentation rate (ESR) in 69 patients with active IBD.

Figure 3

Logistic regression analysis to determine the relationship between TI and anti-TI-ab in patients with IBD.

Figure 4

Simple regression analysis for the relationship between plasma CF concentration and TI-ab in 18 patients with active IBD.