Background Recently, a dramatic increase in HER2 expression in the glomeruli and in the tubular compartment of patients with lupus nephritis was observed. A similar pattern was not seen in patients with IgA nephropathy, post-streptococcal glomerulonephritis or granulomatosis with polyangiitis. HER2 overexpression was also found in NZM2410 mice and it correlated with disease activity. In vitro, IRF1 and α-interferon increased HER2 expression in human mesangial cells and HER2 regulated the levels of miR-26a and miR-30b. These miRNAs control mesangial cell proliferation, by regulating the expression of several genes, including those controlling cell cycle. It was also found that urinary HER2 levels were increased in patients with active lupus nephritis in an adult cohort and correlated with the urine protein:creatinine ratio and with the levels of MCP-1 and VCAM-1.
Objectives Determine the role of HER2 as a urinary biomarker for lupus nephritis activity.
Methods This is an interim analysis of a prospective, multicentric study, of patients with juvenile-onset systemic lupus erythematosus with biopsy-proven lupus nephritis. Urine samples were collected from patients at every clinical visit and also from age-sex matched controls. The samples were centrifuged and the 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. Unpaired and paired t tests were used for the comparisons between samples. The relationship between HER2 and disease activity was defined by Pearson's correlation and linear regression.
Results Urinary HER2 is significantly increased in children with lupus nephritis (N=15) when compared to controls (N=24) (p=0.003). Furthermore, our preliminary data from patients analyzed at different visits showed that HER2 levels tend to reflect disease activity.
Conclusions HER2 was significantly increased in the urine of children with lupus nephritis and its levels changed between visits, reflecting disease activity. Further studies are necessary to determine if HER2 levels can be clinically useful, namely if they can predict the occurrence of a flare. These findings also support the study of anti-HER2 drugs for cell proliferation control in lupus nephritis.
Costa Reis P, Russo PA, Zhang Z et al. The role of microRNAs and Human Epidermal Growth Factor Receptor 2 in Proliferative Lupus Nephritis. Arthritis Rheumatol. 2015 Sep;67(9).
Disclosure of Interest None declared