Posttransplantation relapse of FSGS is characterized by glomerular epithelial cell transdifferentiation.
This study examined six cases of idiopathic nephrotic syndrome with primary lesions of focal segmental glomerulosclerosis (FSGS) that relapsed after renal transplantation. The glomerular lesions comprised the cellular, the collapsing, and the scar variants of FSGS and showed shedding of large round cells into Bowman's space and within the tubular lumens. Immunohistochemistry and confocal laser microscopy carried out on kidneys with FSGS relapse disclosed several phenomena. (1) Some podocytes that expressed podocalyxin, synaptopodin, and glomerular epithelial protein-1 were detached from the tuft and were free in the urinary space. (2) In the cellular variant, most podocytes had lost podocyte-specific epitopes (podocalyxin, synaptopodin, glomerular epithelial protein-1, Wilm's tumor protein-1, complement receptor-1, and vimentin). In the scar variant, these podocyte markers were absent from cobblestone-like epithelial cells and from pseudotubules. (3) Podocytes had acquired expression of various cytokeratins (CK; identified by the AE1/AE3, C2562, CK22, and AEL-KS2 monoclonal antibodies) that were not found in the podocytes of control glomeruli. Parietal epithelial cells expressed AE1/AE3 CK that were faintly, if ever, found on the parietal epithelial cells of normal glomeruli. (4) Numerous cells located at the periphery of the tuft or free in Bowman's space and within tubular lumens expressed macrophagic epitopes (identified by PGM1 [CD68], HAM56, and 25F9 monoclonal antibodies). These macrophage-like cells expressed the activation epitopes HLA-DR and CD16. (5) A number of these cells coexpressed podocalyxin + AE1/AE3 CK, podocalyxin + CD68, and CD68 + AE1/AE3. These findings suggest that in primary FSGS relapsing on transplanted kidneys, some "dysregulated" podocytes, occasionally some parietal epithelial cells, and possibly some tubular epithelial cells undergo a process of transdifferentiation. This process of transdifferentiation was especially striking in podocytes that acquired macrophagic and CK epitopes that are absent from normal adult and fetal podocytes.
Bariéty
Jean
J
University Hospital Broussais and INSERM U 430, Paris, France.
Bruneval
Patrick
P
University Hospital Broussais and INSERM U 430, Paris, France.
Hill
Gary
G
University Hospital Broussais and INSERM U 430, Paris, France.
Irinopoulou
Theano
T
University Hospital Broussais and INSERM U 430, Paris, France.
Mandet
Chantal
C
University Hospital Broussais and INSERM U 430, Paris, France.
Meyrier
Alain
A
University Hospital Broussais and INSERM U 430, Paris, France.
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017209:Apoptosis; D002454:Cell Differentiation; D003402:Creatine Kinase / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology; D000939:Epitopes; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000009:adverse effects*; D008264:Macrophages / Q000502:physiology; D018613:Microscopy, Confocal; D017452:Receptors, IgG / Q000032:analysis; D012008:Recurrence; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003402:Creatine Kinase; D000939:Epitopes; D017452:Receptors, IgG; C067980:CD68 antigen, human; D000097382:CD68 Molecule