Identification of New Biomarkers in Haemophilic Arthropathy Through Transcriptome Analysis

Chronic arthropathy is one of the most common complications of haemophilia, affecting up to 90 per cent of patients aged 4 years and over in at least one joint. The joints most commonly affected are the elbows, knees and ankles. Despite the significant progress made in recent decades in the management of the condition, arthropathy remains one of the main unresolved problems associated with haemophilia.

It is well established that prophylaxis with factor VIII is effective in reducing the risk of joint bleeds and, particularly when started early, is capable of preserving joint structure and function. However, even a single episode of joint bleeding is sufficient to cause irreversible changes to the synovial membrane and predisposes the patient to subsequent bleeds, leading to the development of histopathological changes such as hypertrophy, villous formation, angiogenesis and inflammatory infiltration, and ultimately the onset of chronic arthropathy.

The study aims to assess gene expression in biological samples obtained via synovectomy and joint replacement surgery, and in peripheral blood, from patients with severe haemophilia A or B; to compare these data with those from patients with osteoarthritis and rheumatoid arthritis; and to correlate the gene expression data with information relating to the clinical -laboratory findings, a history of inhibitors, and ultrasound and histological findings.

Endpoints:

• To establish a correlation between the expression of genes associated with inflammation and angiogenesis, as assessed in biopsy samples or synovial fluid, and the severity of haemophilic arthropathy;
• To establish a correlation between the expression of genes associated with inflammation and angiogenesis, as assessed in peripheral blood, and the severity of haemophilic arthropathy.
• In order to assess gene expression in inflammatory and fibrosis pathways - given that it is not possible to obtain samples from healthy individuals - transcriptomic data will be compared with data obtained from samples of osteoarthritis and rheumatoid arthritis as controls for degenerative and inflammatory diseases, respectively.