Antibody-mediated allograft rejection: Morphologic spectrum and serologic correlations in surveillance and for cause biopsies

John C. Papadimitriou, Cinthia B. Drachenberg, Emilio Ramos, Debra Kukuruga, David K. Klassen, Richard Ugarte, Joseph Nogueira, Charles Cangro, Matthew R. Weir, Abdolreza Haririan

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Subclinical antibody-mediated allograft rejection (AMR) has been characterized in serial biopsies from presensitized recipients but has not been systematically studied in conventional renal transplants. METHODS: We evaluated 1101 consecutive kidney transplant biopsies (400 surveillance biopsies [SBx] and 701 for cause biopsies [FCBx]) with concurrent donor-specific antibody (DSA) studies, C4d staining, and ultrastructural examination. RESULTS: A comparison of AMR-related features (DSA and DSA class, C4d staining, and microvascular injury) demonstrated that these were qualitatively and quantitatively associated with each other and with graft dysfunction. A major difference between SBx and FCBx was that the complete AMR phenotype was more common in FCBx. Among SBx, 8.5% showed complete or incomplete AMR with predominance of an incomplete phenotype (according to the Banff schema, these were acute AMR [23.5%], chronic active AMR [14.7%], suspicious for acute AMR [41.1%], suspicious for chronic active AMR [2.9%], and only microvascular injury insufficient to consider AMR [17.5%]). Persistence or worsening of AMR in a subsequent biopsy occurred in 38.2% of cases independently of the strength of AMR findings in the first biopsy (e.g., progression to chronic AMR occurred also in cases with suspicious or nondiagnostic findings). Temporal progression from subclinical to clinically evident AMR is consistent with the fact that, overall, the biopsies with incomplete phenotype (DSA±C4d) occurred between 14.52 and 20.86 months, whereas the complete phenotype occurred much later (36.71 months). CONCLUSION: An accurate diagnostic interpretation of the potentially important but incomplete, subclinical, AMR phenotype represents a serious challenge that may impact clinical management.

Original languageEnglish (US)
Pages (from-to)128-136
Number of pages9
JournalTransplantation
Volume95
Issue number1
DOIs
StatePublished - Jan 15 2013
Externally publishedYes

Fingerprint

Allografts
Biopsy
Antibodies
Phenotype
Transplants
Staining and Labeling
Kidney
Immunoglobulin Isotypes
Wounds and Injuries

Keywords

  • Banff grading schema
  • C4d
  • Capillaritis
  • CD68
  • Donor-specific antibody
  • Endothelial injury
  • Glomerular macrophages
  • Glomerulitis
  • HLA class I
  • HLA class II
  • Mean fluorescence index
  • Microvascular inflammation
  • Transplant glomerulopathy

ASJC Scopus subject areas

  • Transplantation

Cite this

Papadimitriou, J. C., Drachenberg, C. B., Ramos, E., Kukuruga, D., Klassen, D. K., Ugarte, R., ... Haririan, A. (2013). Antibody-mediated allograft rejection: Morphologic spectrum and serologic correlations in surveillance and for cause biopsies. Transplantation, 95(1), 128-136. https://doi.org/10.1097/TP.0b013e3182777f28

Antibody-mediated allograft rejection : Morphologic spectrum and serologic correlations in surveillance and for cause biopsies. / Papadimitriou, John C.; Drachenberg, Cinthia B.; Ramos, Emilio; Kukuruga, Debra; Klassen, David K.; Ugarte, Richard; Nogueira, Joseph; Cangro, Charles; Weir, Matthew R.; Haririan, Abdolreza.

In: Transplantation, Vol. 95, No. 1, 15.01.2013, p. 128-136.

Research output: Contribution to journalArticle

Papadimitriou, JC, Drachenberg, CB, Ramos, E, Kukuruga, D, Klassen, DK, Ugarte, R, Nogueira, J, Cangro, C, Weir, MR & Haririan, A 2013, 'Antibody-mediated allograft rejection: Morphologic spectrum and serologic correlations in surveillance and for cause biopsies', Transplantation, vol. 95, no. 1, pp. 128-136. https://doi.org/10.1097/TP.0b013e3182777f28
Papadimitriou, John C. ; Drachenberg, Cinthia B. ; Ramos, Emilio ; Kukuruga, Debra ; Klassen, David K. ; Ugarte, Richard ; Nogueira, Joseph ; Cangro, Charles ; Weir, Matthew R. ; Haririan, Abdolreza. / Antibody-mediated allograft rejection : Morphologic spectrum and serologic correlations in surveillance and for cause biopsies. In: Transplantation. 2013 ; Vol. 95, No. 1. pp. 128-136.
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AU - Ramos, Emilio

AU - Kukuruga, Debra

AU - Klassen, David K.

AU - Ugarte, Richard

AU - Nogueira, Joseph

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N2 - BACKGROUND: Subclinical antibody-mediated allograft rejection (AMR) has been characterized in serial biopsies from presensitized recipients but has not been systematically studied in conventional renal transplants. METHODS: We evaluated 1101 consecutive kidney transplant biopsies (400 surveillance biopsies [SBx] and 701 for cause biopsies [FCBx]) with concurrent donor-specific antibody (DSA) studies, C4d staining, and ultrastructural examination. RESULTS: A comparison of AMR-related features (DSA and DSA class, C4d staining, and microvascular injury) demonstrated that these were qualitatively and quantitatively associated with each other and with graft dysfunction. A major difference between SBx and FCBx was that the complete AMR phenotype was more common in FCBx. Among SBx, 8.5% showed complete or incomplete AMR with predominance of an incomplete phenotype (according to the Banff schema, these were acute AMR [23.5%], chronic active AMR [14.7%], suspicious for acute AMR [41.1%], suspicious for chronic active AMR [2.9%], and only microvascular injury insufficient to consider AMR [17.5%]). Persistence or worsening of AMR in a subsequent biopsy occurred in 38.2% of cases independently of the strength of AMR findings in the first biopsy (e.g., progression to chronic AMR occurred also in cases with suspicious or nondiagnostic findings). Temporal progression from subclinical to clinically evident AMR is consistent with the fact that, overall, the biopsies with incomplete phenotype (DSA±C4d) occurred between 14.52 and 20.86 months, whereas the complete phenotype occurred much later (36.71 months). CONCLUSION: An accurate diagnostic interpretation of the potentially important but incomplete, subclinical, AMR phenotype represents a serious challenge that may impact clinical management.

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KW - Mean fluorescence index

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KW - Transplant glomerulopathy

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