ESPN 54th Annual Meeting

ESPN 2022


 
Urinary HER2: a new biomarker of pediatric lupus nephritis activity
Patricia Costa-Reis 1 Kelly Maurer 2 Michelle A. Petri 3 Jon M. Burnham 2 Kathleen O’Neil 4 Marisa Klein-Gitelman 5 Emily von Scheven 6 Laura E. Schanberg 7 Kathleen E. Sullivan 1

1- Hospital de Santa Maria, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
2- Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, USA
3- Johns Hopkins University School of Medicine, Baltimore, USA
4- Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, USA
5- Children’s Hospital of Chicago, Northwestern Feinberg School of Medicine, Chicago, USA
6- University of California, San Francisco, USA
7- Duke Children’s Health Center, Durham, USA
 
Introduction:

 

Detecting active lupus nephritis in a background of pre-existing renal damage is challenging, so new biomarkers are much needed to guide clinical practice. Recently, we showed that HER2 (Human Epidermal Growth Factor Receptor 2) is highly expressed in the glomeruli and in the tubular compartment of patients with lupus nephritis and in a lupus mouse model (NZM2410), but not in healthy individuals or patients with other mesangioproliferative glomerulonephritides. Furthermore, we showed, in vitro, that HER2 controls mesangial cell proliferation through miR-26a and miR-30b. In this study, we explored the clinical utility of urinary HER2 (uHER2) as a biomarker of lupus nephritis activity.

Material and methods:

 

Prospective, multicenter, study of children and adolescents with biopsy-proven lupus nephritis. Clinical data and urine were collected periodically and uHER2 was quantified by ELISA. The control groups were: healthy individuals, patients with polyarticular juvenile idiopathic arthritis (JIA) and patients submitted to bone marrow transplant with acute kidney injury (AKI). A validation study was performed in an adult cohort.

Results:

 

We studied 771 samples of 113 children and adolescents with lupus nephritis (81% female; median age 15; 41% class IV). uHER2 was significantly increased in patients with active lupus nephritis (renal-SLEDAI≥4; p=0.006) and not in children with AKI (n=50), JIA (n=20) or healthy controls (n=40). uHER2 levels were associated with casts, hematuria and new onset proteinuria (p<0.05). Furthermore, uHER2 was significantly elevated in clinical visits prior to a renal SLEDAI≥4 (p<0.05).

In adults with SLE (n=189; 126 with lupus nephritis) uHER2 was significantly increased when nephritis was active when compared with patients with renal-SLEDAI 0 or healthy controls.

Conclusions:

 

In this prospective study of a large cohort of pediatric patients with lupus nephritis we showed that uHER2 is a biomarker of disease activity. This might be a new useful tool for clinical practice.