Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss

A. Nocera, A. Tagliamacco, M. Cioni, A. Innocente, I. Fontana, Giancarlo Barbano, Alba Maria Carrea, Miriam Ramondetta, Angela Rita Sementa, Sabrina Basso, Giuseppe Quartuccio, Catherine Klersy, M. Bertocchi, Enrico Verrina, G. Garibotto, Gian Marco Ghiggeri, Massimo Cardillo, Patrizia Comoli, F. Ginevri

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens. A significantly higher homing capability was expressed by class II sDSAs endowed with high mean fluorescence intensity and C3d- and/or C1q-fixing properties. In patients with available sequential biopsy specimens, we detected gDSAs before the appearance of antibody-mediated rejection. In sDSA-positive patients, gDSA positivity did not allow stratification for antibody-mediated graft lesions and graft loss. However, a consistent detection of skewed unique DSA specificities was observed over time within the graft, likely responsible for the damage. Our results indicate that gDSAs could represent an instrumental tool to identify, among sDSAs, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management.

Original languageEnglish
Pages (from-to)692-702
JournalAmerican Journal of Transplantation
Volume17
Issue number3
DOIs
Publication statusPublished - 2017

Fingerprint

Tissue Donors
Transplants
Kidney
Antibodies
Serum
Biopsy
Antibody Specificity
Kidney Transplantation
Fluorescence
Pediatrics
Technology
Wounds and Injuries

Keywords

  • Alloantibody
  • Biomarker
  • Biopsy
  • Clinical research/practice
  • Kidney transplantation/nephrology
  • Monitoring: immune
  • Pediatrics
  • Rejection: antibody-mediated (ABMR)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

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title = "Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss",
abstract = "Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72{\%} of biopsy specimens. A significantly higher homing capability was expressed by class II sDSAs endowed with high mean fluorescence intensity and C3d- and/or C1q-fixing properties. In patients with available sequential biopsy specimens, we detected gDSAs before the appearance of antibody-mediated rejection. In sDSA-positive patients, gDSA positivity did not allow stratification for antibody-mediated graft lesions and graft loss. However, a consistent detection of skewed unique DSA specificities was observed over time within the graft, likely responsible for the damage. Our results indicate that gDSAs could represent an instrumental tool to identify, among sDSAs, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management.",
keywords = "Alloantibody, Biomarker, Biopsy, Clinical research/practice, Kidney transplantation/nephrology, Monitoring: immune, Pediatrics, Rejection: antibody-mediated (ABMR)",
author = "A. Nocera and A. Tagliamacco and M. Cioni and A. Innocente and I. Fontana and Giancarlo Barbano and Carrea, {Alba Maria} and Miriam Ramondetta and Sementa, {Angela Rita} and Sabrina Basso and Giuseppe Quartuccio and Catherine Klersy and M. Bertocchi and Enrico Verrina and G. Garibotto and Ghiggeri, {Gian Marco} and Massimo Cardillo and Patrizia Comoli and F. Ginevri",
year = "2017",
doi = "10.1111/ajt.14000",
language = "English",
volume = "17",
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journal = "American Journal of Transplantation",
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TY - JOUR

T1 - Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss

AU - Nocera, A.

AU - Tagliamacco, A.

AU - Cioni, M.

AU - Innocente, A.

AU - Fontana, I.

AU - Barbano, Giancarlo

AU - Carrea, Alba Maria

AU - Ramondetta, Miriam

AU - Sementa, Angela Rita

AU - Basso, Sabrina

AU - Quartuccio, Giuseppe

AU - Klersy, Catherine

AU - Bertocchi, M.

AU - Verrina, Enrico

AU - Garibotto, G.

AU - Ghiggeri, Gian Marco

AU - Cardillo, Massimo

AU - Comoli, Patrizia

AU - Ginevri, F.

PY - 2017

Y1 - 2017

N2 - Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens. A significantly higher homing capability was expressed by class II sDSAs endowed with high mean fluorescence intensity and C3d- and/or C1q-fixing properties. In patients with available sequential biopsy specimens, we detected gDSAs before the appearance of antibody-mediated rejection. In sDSA-positive patients, gDSA positivity did not allow stratification for antibody-mediated graft lesions and graft loss. However, a consistent detection of skewed unique DSA specificities was observed over time within the graft, likely responsible for the damage. Our results indicate that gDSAs could represent an instrumental tool to identify, among sDSAs, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management.

AB - Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens. A significantly higher homing capability was expressed by class II sDSAs endowed with high mean fluorescence intensity and C3d- and/or C1q-fixing properties. In patients with available sequential biopsy specimens, we detected gDSAs before the appearance of antibody-mediated rejection. In sDSA-positive patients, gDSA positivity did not allow stratification for antibody-mediated graft lesions and graft loss. However, a consistent detection of skewed unique DSA specificities was observed over time within the graft, likely responsible for the damage. Our results indicate that gDSAs could represent an instrumental tool to identify, among sDSAs, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management.

KW - Alloantibody

KW - Biomarker

KW - Biopsy

KW - Clinical research/practice

KW - Kidney transplantation/nephrology

KW - Monitoring: immune

KW - Pediatrics

KW - Rejection: antibody-mediated (ABMR)

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U2 - 10.1111/ajt.14000

DO - 10.1111/ajt.14000

M3 - Article

VL - 17

SP - 692

EP - 702

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 3

ER -