Soluble vascular cell adhesion molecular-1 is a potential biological indicator of hemophilic arthropathy

Abstract

Hemophilic arthropathy is the most common chronic complication in patients with hemophilia. The pathogenesis of hemophilic arthropathy involves the inflammatory processes associated with rheumatoid arthritis (RA). Determining the severity and/or progression of joint damage is crucial when evaluating the effect of treatment modalities. Identifying reliable biomarkers in the peripheral blood of patients with hemophilic arthropathy may be beneficial in clinical practice. Circulating soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin, and P-selectin levels are elevated in patients with RA. Our study investigated whether these soluble adhesion molecules can be used as biological indicators in the course of joint damage in patients with hemophilia A.Patients with hemophilia A (mild, moderate, and severe) were enrolled. The plasma levels of sVCAM-1, E-selectin, and P-selectin in patients with hemophilia A and control were measured using specific enzyme-linked immunosorbent assay kits. Joint damages were evaluated using Pettersson scores.No statistically significant differences were observed in E-selectin and P-selectin levels between patients and controls. The sVCAM-1 level was significantly higher in patients with hemophilia A than in controls. The differences remained significant in patients with severe hemophilia A but not in patients with mild or moderate hemophilia A. The degree of hemophilic arthropathy was evaluated using Pettersson scores, and a score higher than 5 indicated marked arthropathy. Patients with more than 1 joint with marked arthropathy showed significantly higher sVCAM-1 levels.sVCAM-1 levels in patients with hemophilia A are associated with the severity of hemophilic arthropathy.

Figure 1

(A) The plasma sVCAM-1 level was significantly higher in patients with hemophilia A (n = 35) than in controls (n = 20; ^∗∗P = 0.0046). (B) The plasma sVCAM-1 level was significantly higher in patients with severe hemophilia A (n = 22) than in controls (n = 20; ^∗∗P = 0.0047) but was not significantly different between controls and patients with mild (n = 9) or moderate (n = 4) hemophilia A.

Figure 2

Statistical analyses of sVCAM-1 levels were performed after excluding patients with hypertension, hepatitis B infection, and patients not cured of hepatitis C infection. (A) The plasma sVCAM-1 level was significantly higher in patients with hemophilia A (n = 30) than in controls (n = 20; ^∗P = 0.0163). (B) The plasma sVCAM-1 level was significantly higher in patients with severe hemophilia A (n = 17) than in controls (n = 20; ^∗P = 0.0119) but was not significantly different between controls and patients with mild (n = 9) or moderate (n = 4) hemophilia A.

Figure 3

(A) The plasma sE-selectin level was not significantly higher in patients with hemophilia A (n = 28) and controls (n = 9). (B) The plasma sE-selectin level was not significantly higher in patients with mild, moderate, and severe hemophilia A (n = 8, 4, and 16, respectively) and controls (n = 9). (C) The plasma sP-selectin level was not significantly higher in patients with hemophilia A (n = 28) and in controls (n = 9). (D) The plasma sP-selectin level was not significantly higher in patients with mild, moderate, and severe hemophilia A (n = 8, 4, and 16, respectively) than in controls (n = 9).

Figure 4

Statistical analyses of sVCAM-1 levels were performed after grouping by Pettersson score and severity of marked hemophilic arthropathy. The plasma sVCAM-1 level was significantly higher in groups 2 and 3 than in group 1; group 1: Pettersson score of 0 to 4 for every joint, group 2: Pettersson score higher than or equal to 5 for any joint, and group 3: Pettersson score higher than or equal to 5 for more than 2 joints.