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Abstract Number: 1380

Multicenter Prospective Study on the Role of Urinary HER2 As a Lupus Nephritis Biomarker

Patrícia Costa Reis1, Kelly Maurer2, Emily von Scheven3, Kathleen O'Neil4, Jon M. Burnham5, Laura E. Schanberg6, Michelle Petri7 and Kathleen E. Sullivan8, 1Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, 2Immunology ARC 1216, The Children's Hospital of Philadelphia, Philadelphia, PA, 3Division of Rheumatology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, 4Pediatrics, Indiana University, Indianapolis, IN, 5Pediatric Rheumatology, Children's Hospital Philadelphia, Philadelphia, PA, 6Pediatrics, Duke Medical Center, Durham, NC, 7Rheumatology Division, Johns Hopkins University School of Medicine, Baltimore, MD, 8Allergy Immunology, The Children's Hospital of Philadelphia, Philadelphia, PA

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Biomarkers, lupus nephritis and pediatric rheumatology

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Session Information

Date: Monday, November 14, 2016

Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects - Poster II: Myositis, Systemic Lupus Erythematosus, Sjögren's Syndrome

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

HER2 (Human Epidermal Growth Factor Receptor 2) is dramatically overexpressed in the glomeruli and in the tubular compartment of patients with lupus nephritis, but not in other proliferative glomerulonephritides. HER2 expression is also increased in NZM2410 mice and it correlates with disease activity. In human mesangial cells, α-interferon increases HER2 expression, which regulates miR-26a and miR-30b levels. These miRNAs control the expression of cell cycle related genes and consequently regulate mesangial cell proliferation. The dysregulation of this pathway contributes, therefore, to the aberrant mesangial cell proliferation seen in lupus nephritis. Furthermore, in an adult cohort, it was recently shown that urinary HER2 levels were increased in patients with active lupus nephritis and correlated with MCP-1 and VCAM-1 levels.

The goal of this study is to determine the role of HER2 as a urinary biomarker for lupus nephritis activity.

Methods: This is an interim analysis of a prospective study of patients with biopsy-proven lupus nephritis. Data were collected from one adult and four pediatric centers. Urine samples were collected from patients at every clinical visit and also from age-sex matched controls. Urine supernatants were analyzed by enzyme-linked immunosorbent assays for HER2. Clinical data were also collected. The activity of lupus nephritis was measured using renal SLEDAI.

Results: HER2 levels were significantly increased in the urine of lupus nephritis patients (N=135) when compared to controls (N=61) (p=0.003). Moreover, our preliminary prospective data from patients with lupus nephritis analyzed at different visits showed that HER2 levels tend to reflect a renal flare (N=22).

Conclusion: The urinary HER2 levels were significantly increased in patients with lupus nephritis and reflected renal disease activity. This evolving study will further analyse if HER2 levels can be clinically useful, namely if they can predict the occurrence of a flare. Finally, this work also establishes strong foundations to study the use of anti-HER2 drugs to control cell proliferation and damage in lupus nephritis.


Disclosure: P. Costa Reis, None; K. Maurer, None; E. von Scheven, None; K. O'Neil, None; J. M. Burnham, None; L. E. Schanberg, None; M. Petri, None; K. E. Sullivan, None.

To cite this abstract in AMA style:

Costa Reis P, Maurer K, von Scheven E, O'Neil K, Burnham JM, Schanberg LE, Petri M, Sullivan KE. Multicenter Prospective Study on the Role of Urinary HER2 As a Lupus Nephritis Biomarker [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/multicenter-prospective-study-on-the-role-of-urinary-her2-as-a-lupus-nephritis-biomarker/. Accessed .
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