SERPINA3 Protein Could Help Indicate Progression, Severity of Lupus Nephritis in Children

SERPINA3 — a protein involved in inflammation — could serve as an urine indicator of lupus nephritis progression and chronic disease in children, a pilot study suggests.

The study, “Discovery of SERPINA3 as a candidate urinary biomarker of lupus nephritis activity,” was published in the journal Rheumatology.

Up to 80% of children with lupus develop an inflammation of the kidneys called lupus nephritis that can lead to permanent kidney damage if not treated promptly.

The gold standard for a lupus nephritis diagnosis is an invasive kidney biopsy, as traditional measures of lupus nephritis, such as the presence of protein or blood in urine, cannot distinguish between treatable inflammation and irreversible kidney damage.

Researchers have long searched for non-invasive biomarkers that could help determine the level of kidney damage related to lupus nephritis, especially in children.

Recently, advances in proteomics — the study of proteins produced in a given moment and set of conditions — have provided the opportunity to search for biomarkers related to various diseases.

In this pilot study, researchers used proteomics to search for urinary markers that could help determine the level of kidney tissue damage in lupus nephritis patients and differentiate the treatable and chronic forms of the disease.

Investigators collected urine samples of 20 children with different degrees of lupus nephritis and searched for proteins whose levels correlated with disease progression, assessed by a kidney biopsy.

Then, the seven best proteins found in this analysis were validated in another group of 41 patients, median age 16 years, most of whom were women (71%) and had proliferative lupus nephritis (67%).

In this validation group, none of the candidate biomarkers predicted the degree of chronicity of lupus nephritis. However, SERPINA3 levels in urine showed a moderate correlation with lupus nephritis activity. In the kidneys, this protein was found in blood vessels lining affected kidney structures.

SERPINA3 is an extracellular protein that controls inflammation, mainly by inhibiting neutrophils. In the kidney, it inhibits the angiotensin-converting enzyme, possibly helping reduce blood pressure.

Proteins related to SERPINA3, such SERPINA1, are associated with other renal and autoimmune diseases, which suggest that they might play in important role in lupus nephritis.

“Further research is needed to better delineate the role of serpins in the setting of inflammation, i.e. determine whether serpins help control inflammation or contribute to increased persistent inflammation or instead play more specific roles. While we understand that serpins certainly function in acute inflammation, less is known regarding a potential role in chronic disease,” the researchers said.

“Urine SERPINA3 holds potential as a novel biomarker of LN activity,” researchers stated. Still, they caution that more studies are needed to validate the findings in larger cohorts and to study the role of SERPINA3 in the development of lupus nephritis.