Abstract
Objective Hemophilic arthropathy is characterized by recurrent bleeding episodes in patients with hemophilia leading to irreversible joint degeneration. The involvement of CX3CL1 (fractalkine) and its receptor CX3CR1 was observed in the pathogenesis of numerous arthritis-associated diseases. Taking this into account, we have presented a study investigating the role of the CX3CL1/CX3XR1 axis in the course of hemophilic arthropathy, including the CX3CL1-dependent expression of CD56+, CD68+, and CD31+ cells along with evaluation of articular cartilage and synovial membrane morphology. Methods The study was carried out using cases (n = 20) of end-stage hemophilic arthropathy with a severe type of hemophilia A and control cases (n = 20) diagnosed with osteoarthritis. The biofluids including blood serum and synovial fluid were obtained intraoperatively for the evaluation of CX3CL1 using the ELISA test. Tissue specimens including articular cartilage and synovial membrane were similarly collected during surgery and stained immunohistologically using selected antibodies including anti-CX3CR1, anti-CD56, anti-CD68, and anti-CD31. Additionally, the analysis included the assessment of articular cartilage, synovial membrane, and blood vessel morphology. Results In our study, we have documented increased average concentration of CX3CL1 in the blood serum of the study group (7.16 ± 0.53 ng/ml) compared to the control group (5.85 ± 0.70 ng/ml) without statistically significant difference in synovial fluid concentration at the same time. We have observed an increased macrophage presence with more marked proliferation and fibrosis of the synovial membrane in the study group. Remaining results such as expression of CX3CR1 presence of NK cells and larger surface area of blood vessels within the synovial membrane were noted also without statistical significance. Conclusions This study has demonstrated collective CX3CL1/CX3CR1 axis involvement in hemophilic arthropathy pathogenesis introducing new interesting diagnostics and a therapeutic target.
Highlights
The pathophysiology of hemophilia covers a sex-linked inherited coagulation disorder caused by the reduced levels of plasma glycoproteins including the coagulation factor VIII (FVIII) leading to the development of hemophilia A and the analogous reduced levels of coagulation factor IX (FIX) leading to the development of hemophilia B (Christmas disease) [1]
According to the obtained data, the average concentration of CX3CL1 in the serum was elevated in the study group (7:16 ± 0:53 ng/ ml) of hemophilic arthropathy (HA) patients compared to the control group (5:85 ± 0:70 ng/ml) of OA patients which was a statistically significant (p = 0:000078) difference (Figure 1(a))
We think that the complete elucidation of the role of CX3CL1 and CX3CR1 in the pathogenesis of HA and other joint pathologies necessitates much more research based on reliable methodology and larger patient groups and studies including experimental models to demonstrate the specific role of the CXRCL1/CX3CR1 axis in hemophilic arthropathy
Summary
The pathophysiology of hemophilia covers a sex-linked inherited coagulation disorder caused by the reduced levels of plasma glycoproteins including the coagulation factor VIII (FVIII) leading to the development of hemophilia A and the analogous reduced levels of coagulation factor IX (FIX) leading to the development of hemophilia B (Christmas disease) [1]. Cytokines seem to play a leading, but not completely clarified, role among various compounds participating in the induction and circuit-specific inflammatory processes in the pathogenesis of HA [9] This heterogeneous group of proteins has a number of features including the activation and proliferation of immune system cells resulting in functional influence of various types and lines of cells through multilevel and complex system of interconnections known as a cytokine network [10]. Reflecting on this, we hypothesize that the elucidation of the possible role of the CX3CL1/CX3CR1 axis in the pathogenesis of HA could provide a new potential supplementary diagnostic marker or therapeutic target [20] According to these facts, we conducted a study in an attempt to evaluate CX3CL1 concentration levels in the serum and synovial fluid along with expression of CX3CR1 in the articular cartilage and synovial membrane in patients with HA and OA which served as a comparative control group. The results of this study that pertain to the evaluation of a possible role of the CX3CL1/CX3CR1 axis in the pathogenesis of HA have been presented in this manuscript
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