HER2 May Be Biomarker of Kidney Disease in Children, Teens with Lupus, Study Suggests

HER2 May Be Biomarker of Kidney Disease in Children, Teens with Lupus, Study Suggests

High levels of a protein called HER2 in the urine can help identify children and adolescents with lupus who are at risk of serious kidney complications, a study suggests.

While the study is still ongoing, the finding suggests that the use of approved HER2 inhibitors such as Tyverb (lapatinib) or Herceptin (trastuzumab) may also be beneficial for pediatric lupus patients. Additional studies are still warranted to further confirm the therapeutic activity of these medicines for lupus patients.

In general, children and teens with lupus have more severe disease symptoms, more years of disease burden, and a higher rate of kidney inflammation. These complications are linked to an increased risk of lupus nephritis, a kidney disease characterized by active and damaging inflammation.

Kidney disease in pediatric patients can often go undetected until it’s too late. Because lupus nephritis can severely affect a patient’s outcome and survival, it is imperative for researchers to find methods to detect kidney disease in its early stages.

Since 2014, the Lupus Foundation of America has been funding a research project studying if HER2 levels in urine may help identify active flares of lupus nephritis. The five-year project is being led by Kathleen Sullivan, MD, PhD, at the Children’s Hospital of Philadelphia.

Early results have already shown that HER2 in the urine identifies lupus nephritis flares with 80% accuracy.

More recently, the team performed a multicenter study that included 100 children with lupus nephritis from five U.S. academic centers and 91 age-matched healthy controls. Urine samples were collected over the course of four years, and potential urinary biomarkers of lupus nephritis were measured, including HER2, TWEAK, and VCAM-1.

The study, “CS-33 Performance of urinary HER2 as a biomarker of active proliferative lupus nephritis,” was published in the journal Lupus Science & Medicine.

The team found that children with lupus nephritis had significantly higher levels of HER2 than controls. Children with active kidney disease were found to have even higher urinary HER2 values.

In addition, HER2 levels were more sensitive at detecting lupus nephritis flares than TWEAK and more specific than VCAM-1.

Based on these findings, the team believes that urinary HER2 is “a promising new biomarker for determination of lupus nephritis flare” in children. “These results provide further impetus to explore already-available HER2-inhibiting drugs for the treatment of lupus nephritis,” they said.

Sullivan and her team are currently working with Michele Petri, MD, a professor at Johns Hopkins Medicine in Baltimore, to conduct a similar study in adults with lupus.

Preliminary results collected from 142 patients and 23 healthy controls revealed that adult lupus patients also have increased levels of urinary HER2, with the difference also being greatest in patients with active lupus nephritis.

During the final year of the LFA-funded project, the team will continue their investigation to further assess the potential of HER2 as a biomarker for lupus nephritis.

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