Next generation sequencing and functional analysis of patient urine renal progenitor-derived podocytes to unravel the diagnosis underlying refractory lupus nephritis.
Often the cause of refractory lupus nephritis (RLN) remains unclear. We performed next-generation sequencing for podocyte genes in an RLN patient and identified compound heterozygosity for APOL1 risk alleles G1 and G2 and a novel homozygous c.[1049C>T]+[1049C>T] NPHS1 gene variant of unknown significance. To test for causality renal progenitor cells isolated from urine of this patient were differentiated into podocytes in vitro. Podocytes revealed aberrant nephrin trafficking, cytoskeletal structure and lysosomal leakage, and increased detachment as compared with podocytes isolated from controls. Thus, lupus podocytopathy can be confirmed as a cause of RLN by functional genetics on patient-derived podocytes.
Department of Biomedical Experimental and Clinical Sciences 'Mario Serio', Florence, Italy Nephrology and Dialysis Unit, Meyer Children's University Hospital, Florence, Italy.
Paola
P
Romagnani
Department of Biomedical Experimental and Clinical Sciences 'Mario Serio', Florence, Italy Medical Genetic Unit, Meyer Children's University Hospital, Florence, Italy.
Sabrina
S
Giglio
Excellence Centre for Research, Transfer and High Education for the Development of De Novo Therapies (DENOTHE), University of Florence, Florence, Italy.
Maria Lucia
ML
Angelotti
Medical Genetic Unit, Meyer Children's University Hospital, Florence, Italy.
Aldesia
A
Provenzano
Nephrology and Dialysis Unit, Meyer Children's University Hospital, Florence, Italy.
Francesca
F
Becherucci
Nephrology and Dialysis Unit, Meyer Children's University Hospital, Florence, Italy.
Benedetta
B
Mazzinghi
Pathologisches Institut, Ludwig-Maximilians Universität, München, Germany.
Susanna
S
Müller
Department of Nephropathology, University of Erlangen-Nürnberg, Erlangen, Germany.
Kerstin
K
Amann
Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der LMU München, Innenstadt, Munich, Germany.
Marc
M
Weidenbusch
Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der LMU München, Innenstadt, Munich, Germany.
Simone
S
Romoli
Excellence Centre for Research, Transfer and High Education for the Development of De Novo Therapies (DENOTHE), University of Florence, Florence, Italy.
Elena
E
Lazzeri
Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der LMU München, Innenstadt, Munich, Germany.
Hans-Joachim
HJ
Anders
D000293:Adolescent; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008181:Lupus Nephritis / Q000175:diagnosis* / Q000209:etiology / Q000652:urine*; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D012008:Recurrence; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
exome; glomerulonephritis; panel; renal progenitors