Syndecan-1 levels may help ID AAV patients at risk of poor prognosis
High levels of protein in blood linked to disease activity, outcomes: Study
High blood levels of the syndecan-1 protein, known to promote the survival of antibody-producing B cells, may help identify ANCA-associated vasculitis (AAV) patients with high disease activity — and those at risk of a poor prognosis — a new study suggests.
The researchers defined two cut-off values of syndecan-1 that could make it possible to identify such AAV cases.
According to the team, patients with high blood levels of the protein had a significantly greater risk of having among the highest scores at diagnosis on a measure of disease activity.
“The strength of the present study is that it is the first to demonstrate the clinical implications of [blood levels of syndecan-1] measured at diagnosis in patients with AAV in estimating vasculitis activity at diagnosis and has the potential to predict all-cause mortality during follow-up,” the researchers wrote, adding, however, that one of the “critical limitations of this study [is] the small number of patients” involved.
Further research involving a greater number of patients is needed, the team noted.
Their study, “Serum syndecan1 has the potential to reflect activity at diagnosis and predict death during follow-up in patients with ANCA-associated vasculitis,” was published in the journal Arthritis Research & Therapy.
Investigating the relationship between syndecan-1 and patient outcomes
In AAV, the immune system wrongly produces self-targeting antibodies that damage blood vessels. B-cells, the immune cells responsible for antibody production, are thought to play a key role in AAV development.
Syndecan-1 is a protein found at high levels in the epithelial cells that cover body surfaces, and in fibroblasts, a type of connective tissue cell. The protein can be released into the bloodstream to enhance the survival and maturation of B-cells. Given that, elevated circulating levels of syndecan-1 may contribute to the progression of diseases like AAV, and serve as a biomarker of disease activity.
Now, researchers in the Republic of Korea examined the relationship between circulating syndecan-1 levels at AAV diagnosis and patients’ outcomes.
Data were analyzed from 79 people with AAV, whose median age at diagnosis was 64. About 60% were women. Among AAV types, 38 patients had microscopic polyangiitis, while 24 had granulomatosis with polyangiitis and 17 had eosinophilic granulomatosis with polyangiitis.
The most common organ involved was the lungs, in 63.3% of patients, followed by ear/nose/throat (51.9%), and kidneys (48.1%). Coexisting disorders included type 2 diabetes, high blood pressure, and altered fat levels in the blood.
Glucocorticoids were given to all but one patient. Cyclophosphamide was the most commonly administered immunosuppressant. During follow-up, which was at least six months, six patients died (7.6%) and 18 (22.8%) experienced worsening of their kidney disease.
Blood levels of syndecan-1 varied from 14.97 to 1,504 nanograms per milliliter (ng/mL).
Patients with higher protein levels at significant risk of poor outcomes
A first analysis revealed that circulating levels of syndecan-1 at the time of diagnosis correlated significantly with the Birmingham vasculitis activity score, known as BVAS. Higher BVAS values indicate more severe disease.
The team then found that patients grouped in the highest third of BVAS values at diagnosis more commonly had a syndecan-1 level of at least 76.1 ng/mL than a lower level (79.2% vs. 14.5%). Using this level as a cut-off had a sensitivity of 70.4% and a specificity of 90.4%. A test’s sensitivity is its ability to correctly identify those with a given disease, while its specificity refers to the percentage of unaffected cases being correctly ruled out.
Overall, patients with levels of at least 76.1 ng/mL of syndecan-1 had a significantly higher risk — about 22 times — of having the highest third of BVAS scores at diagnosis.
When BVAS scores were divided in two, the optimal cutoff of blood syndecan-1 was set as 60 ng/mL, with a sensitivity of 64.4% and a specificity of 79.4%.
A syndecan-1 cut-off of 120.1 ng/mL at diagnosis identified patients at risk of death from any cause with a sensitivity of 83.3% and a specificity of 87.7%. Death due to any cause was significantly higher among patients with syndecan-1 levels of 120.1 ng/mL or higher compared with those with lower levels (35.7% vs. 1.5%). The risk of death was about 35 times higher in patients with syndecan-1 levels above this threshold.
This study is the first to demonstrate that [blood syndecan-1] at diagnosis may not only reflect AAV activity at diagnosis but may also be associated with all-cause mortality during follow-up.
In a multivariate analysis — one based on the relationship between several variables — altered levels of fat molecules showed a tendency to be associated with death due to any cause.
In addition to the small number of patients involved, the researchers cited the study’s retrospective design as a “critical” limitation. The team called for “future prospective studies with more patients and [additional] clinical data.”
Still, the scientists noted that “this study is the first to demonstrate that [blood syndecan-1] at diagnosis may not only reflect AAV activity at diagnosis but may also be associated with all-cause mortality during follow-up.”
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