Plasma levels of IL-1β and IL-37 in patients with severe haemophilia

Abstract

Objective: Haemophilia A and B are disorders caused by the lack of clotting factors VIII and IX, respectively. Repeated bleeding into the same joint leads to haemophilic arthropathy (HA). Interleukin (IL)-1β is responsible for the pro-inflammatory response and IL-37 is induced by IL-1β stimuli to have an anti-inflammatory response and prevent uncontrolled inflammation and tissue damage. Our objective was to investigate plasma levels of IL-1β and IL-37 in patients with severe haemophilia with different severities of HA.

Methods: Peripheral blood samples were collected from 14 patients with severe haemophilia A and 6 with severe haemophilia B, and 18 healthy individuals. Plasma levels of IL-1β and IL-37 were detected by immunoassay, and severity of HA was evaluated using the Pettersson scoring system. Plasma levels of IL-1β and IL-37 were analysed in patients with severe haemophilia grouped by Pettersson score and in healthy individuals.

Results: Plasma levels of IL-1β and IL-37 were significantly higher in patients with severe haemophilia compared with healthy individuals and significantly lower in those with moderate to severe HA than in those with no or mild HA.

Conclusions: Plasma levels of IL-1β and IL-37 may be useful to track HA progression in patients with severe haemophilia.

Keywords: Haemophilia; Pettersson score; cytokine; haemophilic arthropathy; interleukin-1β; interleukin-37.

Figure 1.

Analysis of plasma levels of interleukin (IL)-1β and IL-37 between patients with severe haemophilia and healthy individuals. IL-1β and IL-37 plasma levels were significantly higher in patients with severe haemophilia (n = 20) than in healthy individuals (n = 18). *p < 0.05.

Figure 2.

Analysis of interleukin (IL)-1β and IL-37 plasma levels in patients with different Pettersson score (indicating severity of haemophilic arthropathy) profiles. Plasma levels of IL-1β and IL-37 were significantly higher in Pettersson group A or group B patients than in healthy individuals and significantly lower in Pettersson group B patients than in Pettersson group A patients. *p < 0.05 compared with healthy individuals; ^#p < 0.05 compared with Pettersson group A patients. Group A represents patients with a Pettersson score <5 for all joints; Group B represents patients with a Pettersson score ≥5 for any joint.

Figure 3.

Correlation between cytokine levels and Pettersson score (indicating severity of haemophilic arthropathy). We found negative correlations between interleukin (IL)-1β (r² = 0.2374; p = 0.0294) and IL-37 (r² = 0.2431; p = 0.0272) plasma levels and the sum of Pettersson scores. We found a positive correlation between IL-1β and IL-37 plasma levels (r² = 0.7196; p < 0.0001). The sum of Pettersson scores represents the total scores of six joints (bilateral elbows, bilateral ankles, and bilateral knees).