Patterns of nephrin and a new proteinuria-associated protein expression in human renal diseases.
BACKGROUND
Many factors contribute to the pathogenesis of glomerular proteinuria, but no exact molecular mechanisms are known to date. The recently reported protein nephrin, encoded by the NPHS1 gene, appears to be crucial for the integrity of the glomerular filtration barrier.


METHODS
Immunohistochemistry was used to detect possible changes in glomerular nephrin, and a new proteinuria-associated protein expression was developed in various diagnostic groups of human kidney biopsies.


RESULTS
In normal control kidney, antibodies to intracellular and extracellular nephrin domain showed a typical podocyte pattern of reactivity, while the 18C7 antibody to a normally inaccessible proteinuria-associated epitope was negative. Instead, strong glomerular positivity by 18C7 was seen in membranous glomerulonephropathy, membranoproliferative glomerulonephritis, systemic lupus erythematosus and cryoglobulinemic nephritis, while with antibodies to either intracellular or extracellular nephrin domains, a down-regulation in nephrin expression pattern was shown.


CONCLUSIONS
Unmasking or de novo expression of distinct glomerular proteins may be an important feature reflecting the pathophysiological events in these diseases with altered glomerular permeability, while only mild changes in the slit diaphragm protein nephrin appear to take place.
Wang
Shi-Xuan
SX
Department of Bacteriology and Immunology, Haartman Institute and University Central Hospital, University of Helsinki, Helsinki, Finland.
Rastaldi
Maria P
MP
Pätäri
Anu
A
Ahola
Heikki
H
Heikkilä
Eija
E
Holthöfer
Harry
H
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001706:Biopsy; D000939:Epitopes / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000473:pathology / Q000503:physiopathology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics* / Q000276:immunology; D011507:Proteinuria / Q000473:pathology / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D008565:Membrane Proteins; D011506:Proteins; C113267:nephrin