title: Clinical significance of the distribution of C4d deposits in different anatomic compartments of the allograft kidney.
abstract: Diffuse C4d deposition in peritubular capillaries is a well-recognized marker of antibody-mediated rejection. The significance of staining patterns that are focal or affect non-peritubular capillary compartments is less well defined. Paired frozen section and paraffin-embedded tissue stains were performed in 52 kidney allograft biopsies, and correlated with clinicopathologic parameters. Diffuse peritubular capillary C4d deposits were more often seen in frozen sections (22/52, 43% frozen tissue vs 10/52, 19% paraffin-embedded tissue), whereas focal staining was observed more frequently within paraffin sections (13/52, 25% paraffin-embedded tissue vs 7/52, 14% frozen tissue). In biopsies taken from patients with a history of donor-specific antibodies, diffuse, focal and negative peritubular capillary C4d staining patterns were seen in 11/14 (79%), 1/14 (7%) and 2/14 (14%) of frozen biopsies vs 5/14 (36%), 6/14 (43%) and 3/14 (21%) of paraffin-embedded biopsies. Transplant glomerulopathy score in paraffin-embedded biopsies was higher in specimens with vs without glomerular basement membrane C4d staining (1.5+/-0.8 vs 1.0+/-0.6, P=0.03). Tubular basement membrane staining was present in 4% paraffin-embedded and 48% frozen specimens independent of tubular atrophy. Arteriolar hyalinosis score in paraffin-embedded specimens was higher in biopsies with vs those without arteriolar C4d deposits (1.3+/-0.9 vs 0.9+/-0.8, P=0.04). Arterial staining was unrelated to the degree of intimal thickening. In conclusion, peritubular capillary deposits correlate well with circulating donor-specific antibody. For paraffin-embedded tissue, combining the results of focal and diffuse staining allows a diagnostic sensitivity comparable to diffuse staining in frozen tissue. Finally, C4d deposits preferentially in lesions of chronic transplant glomerulopathy and arteriolar hyalinosis.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Batal
authors.forename: Alin
authors.initials: A
authors.lastname: Girnita
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: Bassel Abou
authors.initials: BA
authors.lastname: Saab
authors.forename: Sean
authors.initials: S
authors.lastname: Stockhausen
authors.forename: Ron
authors.initials: R
authors.lastname: Shapiro
authors.forename: Amit
authors.initials: A
authors.lastname: Basu
authors.forename: Henkie
authors.initials: H
authors.lastname: Tan
authors.forename: Claire
authors.initials: C
authors.lastname: Morgan
authors.forename: Parmjeet
authors.initials: P
authors.lastname: Randhawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D015935:Complement C4b / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005629:Frozen Sections; D050533:Glomerular Basement Membrane / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D007519:Isoantigens / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D007684:Kidney Tubules / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D010446:Peptide Fragments / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014184:Transplantation, Homologous
chemical_list: D007518:Isoantibodies; D007519:Isoantigens; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d