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B-cell protein sBCMA may be useful biomarker of SLE activity in children

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Study finds high levels of this immune system protein in untreated SLE children

by Lindsey Shapiro

Blood levels of an immune system protein called sBCMA were found elevated in untreated children with systemic lupus erythematosus (SLE) compared with treated patients and healthy children in China.

That’s according to a recent study, which also found that sBCMA levels declined after treatment.

Higher levels of the protein were associated with greater disease activity and immune markers in the blood.

The findings support “the clinical exploitation of serum [blood] sBCMA as a biomarker in [childhood SLE],” although additional studies are still needed, researchers noted.

The study, “Serum levels and significance of soluble B-cell maturation antigen in childhood-onset systemic lupus erythematosus with renal involvement,” was published in the journal Lupus.

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Childhood-onset SLE linked to higher disease activity

In SLE, immune B-cells produce self-reactive antibodies that wrongly target body tissues, leading to symptoms affecting multiple organ systems.

Childhood-onset SLE tends to be associated with higher disease activity and a greater prevalence of lupus nephritis, or inflammation in the kidneys.

Certain signaling molecules, namely B-cell activating factor of the TNF family and a proliferation-inducing ligand, are important for the survival and maintenance of B-cells.

Thus, these molecules and the receptors they act upon are thought to be key therapeutic targets in lupus and other autoimmune conditions.

One of these receptors is the B-cell maturation antigen (BCMA), a protein that is normally found on the surface of plasma cells — a type of mature, antibody-producing B-cell — and supports their long-term survival.

More recently, a soluble version of BCMA that’s shed from cell surfaces was identified. Called sBCMA, the protein was found to be elevated in adult SLE patients and its levels correlated with disease activity in some studies.

It’s thought that sBCMA could therefore be a promising disease biomarker, but its potential role in pediatric patients, particularly those with lupus nephritis, hasn’t been investigated.

In the report, researchers looked at sBCMA levels in the blood of 116 children with SLE and kidney involvement who were seen at a hospital in China from 2014 to 2019, along with 31 healthy children.

The 84 girls and 32 boys with SLE had a median age of 11.6 years, and had been living with the autoimmune disease for a median of 8.5 months. All met the criteria for lupus nephritis.

sBCMA level guarantee its clinical application as a biomarker in pediatric SLE population.

At the time of hospital admission, 100 children were receiving treatment and 16 were untreated.

Among untreated children with SLE, median sBCMA levels were at 130.2 nanograms per milliliter (ng/mL) of blood, which was significantly higher than in healthy children (51.2 ng/mL) or treated SLE patients (47.6 ng/mL).

For 11 children with repeat measurements before and after treatment, a significant 61% decrease in sBCMA levels was observed following treatment.

Higher levels of the protein were correlated weakly, but significantly, with greater disease activity, as measured by the SLE disease activity index-2K.

The 28 children considered to have high disease activity had significantly higher median sBCMA levels (88.4 ng/mL) compared with the 64 children with mild-to-moderate disease activity (45.9 ng/mL) or the 24 with no disease activity (47.6 ng/mL).

sBCMA levels were also correlated with other immune markers in the blood, and weakly associated with certain blood parameters, such as white blood cell and platelet counts.

However, sBCMA levels were not correlated with markers of kidney function.

Using sBCMA as biomarker may be more cost-effective and practical

The researchers noted several advantages of using sBCMA as an SLE biomarker, including that it does not seem to be influenced by age or sex, it’s stable at room temperature, and it’s easy and cost-effective to measure.

Moreover, it doesn’t require a lot of blood to be drawn, making it more practical for children.

“These beneficial features of serum [blood] sBCMA level guarantee its clinical application as a biomarker in pediatric SLE population,” the team wrote.

Still, larger studies with a more diverse patient population are needed, the team noted.

Future studies to investigate the effects of more recently approved SLE therapies, such as Benlysta (belimumab), are also warranted, the researchers wrote.

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