Blood Protein Levels Linked to Disease Activity in Children with SLE and May Be Biomarkers, Study Reports

Blood Protein Levels Linked to Disease Activity in Children with SLE and May Be Biomarkers, Study Reports
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blood biomarkers

Levels of proteins associated with changes in the inner wall of blood vessels — the endothelium —  are higher in children and adolescents with systemic lupus erythematosus (SLE) and are potential biomarkers of disease activity, as well as of brain and kidney involvement, a study suggests.

The study, “Biomarkers associating endothelial Dysregulation in pediatric-onset systemic lupus erythematous,” was published in the journal Pediatric Rheumatology.

Between 10% and 20% of all SLE cases arise during childhood and are associated with more severe disease and faster progression than adult-onset SLE. Adolescents with the disease are also at a significantly higher risk of kidney and neurological complications compared to patients whose disease starts in adulthood.

Researchers are looking for better ways to monitor disease activity, which could improve how SLE is managed in young patients.

The sustained inflammatory reaction in SLE also affects the vascular system. Vasculopathy (disease of the blood vessels) is commonly found in these patients, and associated with serious conditions in vital organs that include the central nervous system (brain and spinal cord).

Vascular disease is often preceded by damage in the endothelium. To explore whether markers of endothelial damage could reflect disease status in young SLE patients, a team from Taiwan used blood samples from those pediatric-onset to compare their endothelium-related proteins levels with samples from healthy controls.

The samples were collected at Chang Gung Memorial Hospital between 2015 and 2018. Mean age at diagnosis of the study’s 118 patients (107 females) was 13 years.

Regarding disease progression, 15 patients (12.7%) showed neurological manifestations and 60 (50.8%) had kidney involvement. A total of 73 (61.9%) patients had lupus nephritis, a type of kidney inflammation and one of the most common manifestations in people with SLE.

Results showed that blood levels of three proteins — Tie2, vascular endothelial growth factor (VEGF), and thrombomodulin — were significantly higher in SLE patients, particularly those with active disease, compared with controls. Of note, Tie2 has been associated with endothelial cell survival and blood vessel formation, VEGF with survival of these cells, and thrombomodulin with endothelial injury.

In contrast, levels of ADAMTS13 (an enzyme involved in blood clotting) were lower in patients with active disease. Lower ADAMTS13 levels is linked to higher disease activity, as measured by the SLE Disease Activity Index (SLEDAI).

Patients with neurological manifestations had lower blood levels of ADAMTS13 (437.8 vs. 544.7 nanograms/ml) than those without these complications.

Researchers also found that thrombomodulin levels were higher in patients with kidney involvement compared to patients without such complications, 6055 vs. 3416 picograms (pg)/ml.

Thrombomodulin levels higher than 4346.79 pg/ml also predicted disease activity better than the amount of anti-double stranded (ds) DNA autoantibodies, a standard parameter of disease activity in pediatric SLE. If higher than 3333.6 pg/ml, thrombomodulin also predicted renal complications better than these autoantibodies, known to correlate with the presence of lupus nephritis.

“[T]he elevation of thrombomodulin in cases with kidney involvement may be explained by a possible pro-thrombotic [blood clotting] tendency and sequential endothelium injury,” the researchers wrote. Its excretion via the kidneys is a likely explanation for why it stood out in this study, they added.

Overall, these results suggest that “endothelial dysregulation associating proteins seems to be potent biomarkers [disease] SLE activity as well as organ involvement in [pediatric]SLE patients,” the team wrote.

“These biomarkers may be beneficial in understanding of the vascular pathogenesis and disease monitoring” the scientists added.

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