CD13 levels elevated in scleroderma, but biomarker value unclear
Study finds soluble CD13 higher in patients but not tied to severity
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Levels of soluble CD13, the circulating form of a protein involved in inflammation and fibrosis (scarring), are generally higher in people with scleroderma, but do not clearly correlate with disease severity or specific clinical features, a new study reports.
The findings suggest that CD13 alone is unlikely to serve as a reliable standalone biomarker for scleroderma, though more research is needed to understand whether it may help track how the disease changes over time.
The study, “Soluble CD13 in systemic sclerosis: clinical observations and transcriptomic insights from peripheral blood,” was published in Arthritis Research & Therapy.Â
What scleroderma is and why CD13 may be involved
Scleroderma, also called systemic sclerosis or SSc, is a disease marked by inflammation and fibrosis that can affect the skin and internal organs. The causes of scleroderma are still not completely understood.
CD13 is a signaling protein known to help regulate inflammation and fibrosis. In this study, the researchers examined whether blood levels of soluble CD13 (sCD13) are altered in people with scleroderma and whether they correlate with SSc subtypes, blood vessel complications, skin and lung fibrosis, or SSc-specific autoantibodies — immune proteins that mistakenly attack the body’s own tissues.
The researchers first analyzed plasma CD13 levels in 30 people: 10 with limited scleroderma, 10 with more severe diffuse scleroderma, and 10 healthy individuals. The groups were matched for factors such as age and sex. Here, the researchers found that CD13 levels were significantly higher in participants with diffuse scleroderma than in those with limited disease, but neither group showed significantly higher levels when compared with healthy controls.
In a larger group designed to evaluate blood vessel complications, blood levels of CD13 were significantly higher in people with scleroderma than in controls, but no difference was seen between disease subtypes. Likewise, in a third group of patients with early-stage scleroderma, CD13 levels were again elevated compared with controls, but did not differ between disease subtypes.
“Altogether, significant elevation of sCD13 in SSc patients compared to healthy controls was consistently observed, however there was no difference between disease subtypes,” the team wrote.
Higher CD13 levels not clearly tied to disease severity
The researchers then examined whether blood levels of soluble CD13 were linked to disease severity or clinical features. Overall, most analyses found no significant associations.
However, patients with higher CD13 levels at the initial assessment tended to show greater improvement in skin fibrosis scores over the following year, as measured by the modified Rodnan skin score. This “suggests that higher circulating [CD13] may be associated with greater potential for improvement in skin fibrosis,” the researchers wrote. This finding was unexpected given that CD13 is thought mainly to promote fibrosis, so the researchers called for further tests to better understand its specific role in scleroderma.
Additional analyses showed that CD13 levels tended to decrease over time, and larger decreases were associated with greater improvement in skin fibrosis scores. However, larger declines in CD13 were also linked to worsening lung function, highlighting that changes in skin and lung involvement may not follow the same pattern.
This suggests “that skin involvement may not reliably indicate overall disease severity and that its progression does not parallel [lung] outcomes,” the scientists wrote. “These findings also suggest that [CD13] may vary over time and that its relationship with skin and lung fibrosis may depend on the disease phase.”
CD13 linked to inflammatory activity in specific immune cells
In further analyses, the researchers examined gene activity from public datasets to better understand how CD13 is involved in scleroderma. They found that CD13-related gene activity was closely linked to inflammatory pathways, particularly in myeloid cells — a type of immune cell involved in inflammation and tissue damage.
These findings suggest that examining CD13-related activity in specific cell types may be more informative than simply measuring levels of the protein in a blood sample. This is because the protein’s role may depend on where it is active in the body, and blood levels alone may not fully reflect the disease processes occurring in affected tissues. “The discrepancy between systemic [body-wide CD13] levels and tissue-level fibrotic activity underscores the importance of local context in interpreting biomarker data,” the investigators added.
Overall, the scientists said more research is needed to better understand how CD13 contributes to scleroderma.
