title: Tubular and endothelial chimerism in renal allografts using fluorescence and chromogenic in situ hybridization (FISH, CISH) technology.
abstract: The role of endothelial and tubular chimerism in renal allograft adaptation and rejection varies in different studies. We addressed the correlation between different clinico-pathological settings and sex-chromosomal endothelial and/or tubular chimerism in renal allografts. We examined the presence or absence of the X and Y chromosomes by fluorescence and chromogenic in situ hybridization (FISH, CISH) methodology on paraffin embedded kidney biopsies in 16 gender mismatched renal transplants (1 to 12 years post-transplantation). Twelve patients were male, four female. Four groups were selected: (i) Vascular calcineurin inhibitor toxicity without rejection; (ii) T-cell mediated vascular rejection; (iii) antibody mediated rejection; and (iv) C4d-positivity in AB0-incompatible transplants with or without rejection. Twelve non-transplant kidney biopsies (8 female, 4 male) were used as controls. Tubular chimerism was detected more frequently (69%) than endothelial chimerism (12%) in renal transplants. One of 12 control patients had tubular and endothelial chimeric cells (8%). The Y chromosome occurred in 8/12 male recipients (67%) in tubular epithelial cells and in 5/12 male recipients (42%) in endothelial cells. Double X chromosomes were detected in 3/4 female recipients in tubular epithelium. Tubular chimerism occurred more often with endothelial chimerism and capillaritis without correlation with other parameters, such as rejection. Combined Y chromosomal tubular and lymphatic endothelial chimerism correlated with T-cell mediated vascular rejection in two out of three patients (66%). Combined Y chromosomal tubular and peritubular capillary chimerism correlated with antibody mediated C4d+ rejection in one out of two patients (50%). Tubular and/or endothelial chimerism occur frequently in gender mismatched renal allografts and, when combined, this is associated with T-cell mediated rejection.
authors.affiliation: Institute of Surgical Pathology, Department Pathology, University Hospital Zurich, Zurich, Switzerland. zsuzsanna.varga@usz.ch
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Varga
authors.forename: Ariana
authors.initials: A
authors.lastname: Gaspert
authors.forename: Silvia
authors.initials: S
authors.lastname: Behnke
authors.forename: Adriana
authors.initials: A
authors.lastname: von Teichman
authors.forename: Florian
authors.initials: F
authors.lastname: Fritzsche
authors.forename: Thomas
authors.initials: T
authors.lastname: Fehr
mesh_terms: D000328:Adult; D019703:Calcineurin / Q000009:adverse effects; D002863:Chromogenic Compounds; D041321:Chromosomes, Human, X / Q000235:genetics*; D041322:Chromosomes, Human, Y / Q000235:genetics*; D002908:Chronic Disease; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D017404:In Situ Hybridization, Fluorescence; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018183:Transplantation Chimera / Q000235:genetics*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D002863:Chromogenic Compounds; D007166:Immunosuppressive Agents; D019703:Calcineurin