Brief Communication Antibodies to m-type phospholipase A2 receptor in children with idiopathic membranous nephropathy VINOD KUMAR, 1 * RAJA RAMACHANDRAN, 1 * ASHWANI KUMAR, 2 RITAMBHRA NADA, 2 DEEPTI SURI, 3 ANJU GUPTA, 3 HARBIR SINGH KOHLI, 1 KRISHAN LAL GUPTA 1 and VIVEKANAND JHA 1,4 Departments of 1 Nephrology, 2 Histopathology, 3 Paediatric Allergy and Immunology, Postgraduate Institute of Medical Education & Research, Chandigarh and 4 George Institute for Global Health, New Delhi, India KEY WORDS: glomerulonephritis, membranous nephropathy, nephrotic syndrome, tacrolimus. Correspondence: Professor Vivekanand Jha, George Institute for Global Health, 219-221 Splendor Forum, Jasola, New Delhi 110025, India. Email: vjha@pginephro.org doi:10.1111/nep.12478 *Equal contributions. ABSTRACT: Idiopathic membranous nephropathy (IMN), the commonest cause of adult nephrotic syndrome (NS), accounts for only a minority of paediatric NS. Antibodies to m-type phospholipase A2 receptor (PLA2R) are seen in two-thirds of adult IMN cases. PLA2R staining in glomerular deposits is observed in 74% and 45% of adult and paediatric IMN cases, respectively. However, there are no reports of anti-PLA2R in paediatric IMN. We evalu- ated anti-PLA2R levels and PLA2R in gloemrular deposits in paediatric IMN seen at our center. Five cases were enrolled, all the cases stained for PLA2R in glomeruli and three (60%) had antibodies to PLA2R antigen. There was a parellel reduction in proteinuria and anti-PLA2R titer. The present report suggests that PLA2R has a contributory role in the patho- genesis of paediatric IMN. Membranous nephroapthy (MN) in children is usually sec- ondary to chronic hepatotropic viral diseases or lupus nephritis. Idiopathic membranous nephropathy (IMN) accounts for only 1–2% of nephrotic syndrome in children. 1,2 The compelling role of development of antibodies to m-type phospholipase A2 receptor (PLA2R) in the pathogenesis of IMN has been described in multiple publications. Almost all of this literature, however, has been limited to adults, where this condition is frequent. About 70–74% of adult IMN cases show elevated circulating levels of anti-PLA2R and staining for PLA2R in the glomerulus. 3,4 The circulating antibody levels correlate with disease activity and herald response to treatment, making them useful in diagnosis and follow up. Idiopathic membranous nephropathy is also seen in children and adolescents, albeit less frequently. Immuno- logical reactions against other antigens, such as bovine serum albumin and neural endopeptidase have been shown to be causal in those cases. 5,6 Cossey et al. evaluated staining for PLA2R in glomerular deposits in 22 patients with IMN between the ages of 4 and 17 years, and noted positivity in 45% of cases. 7 The frequency of anti- PLA2R positivity in the paediatric population has not been studied. METHODS This study was done from September 2011 to November 2014. A total of five cases of biopsy-proved IMN in children (≤13 years) were evaluated for circulating anti-PLA2R antibodies (enzyme linked immunosorbent assay (ELISA) and indirect immunofluores- cence (IIF) (EUROMMUN, Germany) (http://www.accessdata.fda .gov/cdrh_docs/reviews/K132379.pdf). All of these children had received steroids (oral prednisolone 2 mg/kg per day for 3–4 weeks) and underwent biopsy only after the nephrotic state was deemed to be steroid-resistant. The baseline blood samples were drawn just before initiation of therapy for IMN. Patients were treated with either Modified Ponticelli regimen 8,9 (intravenous pulse methyl prednisolone (20 mg/kg, to a maximum of 1 g) for 3 days followed by oral prednisolone (0.5 mg/kg per day) for 27 days of the 1st, 3rd and 5th month and oral cyclophosphamide (2 mg/kg per day) for 30 days on the 2nd, 4th and 6th month) or a combination of Tacrolimus (target trough level of 5– 10 ng/mL for 1st 6 months followed by 4–7 ng/mL for next 6 months) and steroids (oral prednisolone 0.5 mg/kg per day for 6 months). 10 For ELISA, diluted (1:101) test samples along with controls were incubated for 30 min followed by washing and incubation with peroxidase labelled anti human IgG. Plates were washed and incu- bated for an additional 15 min with chromogen substrate, and the colour intensity was measured at 450 and 620 nm. For IIF, we used Nephrology 20 (2015) 572–575 © 2015 Asian Pacific Society of Nephrology 572