Protein marker may detect early joint damage in hemophilia A
Study finds YKL-40 levels higher in patients with hemophilic arthropathy
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Measuring levels of YKL-40 — a protein associated with inflammation and tissue remodeling — may help detect hemophilic arthropathy, the joint damage caused by repeated bleeding, in people with severe hemophilia A, a study found.
The researchers said the results “suggest that YKL-40 has potential as a biomarker, with its concentrations corresponding to both the presence and severity of HAP [hemophilic arthropathy].”
The findings were published in a letter to the editor titled, “Circulating and Synovial Fluid Levels of YKL-40 Protein in Patients With Severe Haemophilia A: Preliminary Observations,” in Haemophilia.
Hemophilia A is caused by missing or poorly functioning clotting factor VIII, a protein needed to form blood clots. In severe disease, very low factor VIII levels can lead to spontaneous bleeding, most often into muscles and large joints such as the knees, ankles, and elbows. Repeated joint bleeds can lead to chronic inflammation, which can eventually result in hemophilic arthropathy, a chronic, painful form of joint disease.
Easily detectable markers that could help diagnose and track joint damage earlier or more accurately would represent an important step toward earlier intervention and better long-term joint health.
Comparing protein levels yields discovery
YKL-40 is produced by several cell types involved in inflammation and tissue remodeling, including immune cells and joint tissue cells. The protein has been linked to multiple inflammatory conditions and is elevated in joint fluid across different types of arthritis, suggesting it may be useful for monitoring joint disease.
To test its potential as a biomarker in hemophilia, scientists in Greece compared YKL-40 levels in children and adults with severe hemophilia A, examining YKL-40 levels in both blood and synovial (joint) fluid of those with hemophilic arthropathy.
They recruited 38 boys (mean age 13.9) and 32 adult men (mean age 46.2) with severe hemophilia A, all on preventive treatment, from two hemophilia centers in Athens.
At the time of testing, 18 of the children had no signs of hemophilic arthropathy, while the remaining 20 had joint disease classified as mild or moderate. In contrast, all adults in the study had severe hemophilic arthropathy. The researchers also included 50 age- and sex-matched healthy volunteers who served as controls.
YKL-40 levels rose with age in both groups. Levels were significantly higher in adults with hemophilic arthropathy compared with age-matched healthy controls, with mean values of 80.5 nanograms per milliliter (ng/mL) vs. 31.1 ng/mL.
In children with joint disease, YKL-40 levels were also higher than in healthy children, with mean values of 23.2 versus 17.0 ng/mL.
Within the pediatric group, YKL-40 levels did not differ significantly between mild and moderate arthropathy. However, children with hemophilic arthropathy, regardless of severity, had higher YKL-40 levels than boys with hemophilia without joint disease.
In a subset of adults with severe hemophilic arthropathy, synovial fluid YKL-40 levels were more than 10 times higher than blood levels, ranging from 750 to 1,100 ng/mL. The team also found a moderate link between YKL-40 and high-sensitivity C-reactive protein (hs-CRP), a marker of whole-body inflammation.
Together, the findings suggest that YKL-40 could be a useful biomarker to help identify hemophilic arthropathy — and potentially monitor joint damage — though the researchers noted that larger studies would be needed to confirm its clinical value.
“YKL-40 levels correlate with the presence and the severity of joint destruction and the disease activity in patients with arthropathies,” the researchers wrote. “Monitoring of [YKL-40] levels may provide insights into degree of inflammation … and the potential for tissue repair or further joint deterioration.”
