Recurrence of nephrotic syndrome after transplantation in CNF is due to autoantibodies to nephrin.
The novel gene NPHS1 is defective in the patients with congenital nephrotic syndrome of the Finnish type (CNF) leading to abnormal expression of the respective protein product nephrin in glomerular cells. CNF patients are treated with early nephrectomy and renal transplantation, but about 20% show recurrence of nephrotic syndrome (NS). We used indirect immunofluorescence microscopy and immunoblotting and an ELISA assay to search for circulating autoantibodies to nephrin, the protein defect in CNF patient kidneys. In serial serum samples gathered before and after recurrence of NS, we show an increased antibody titer to nephrin prior to the NS episode and a subsequent drop in antibody level after its successful treatment and reactivity of the high titer sera with glomeruli in indirect immunofluorescence microscopy as well. The results show that the transplantation treatment introduces a neoantigen inducing production of autoantibodies, which may be pathogenic for perturbation of the function of the glomerular filtration barrier.
Wang
S X
SX
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Finland.
Ahola
H
H
Palmen
T
T
Solin
M L
ML
Luimula
P
P
Holthöfer
H
H
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood* / Q000378:metabolism; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009404:Nephrotic Syndrome / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012008:Recurrence
D001323:Autoantibodies; D008565:Membrane Proteins; D011506:Proteins; C113267:nephrin