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, G Barbano, A Carrea, M Ramondetta, A Sementa, S Basso, G Quartuccio, C Klersy, M Bertocchi, E Verrina, G Garibotto, G M Ghiggeri, M Cardillo, P Comoli, F Ginevri

Research output: Contribution to journalArticle

10 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
Number of pages11
JournalAmerican Journal of Transplantation
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 2017

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

Keywords

  • Adolescent
  • Adult
  • Antibody Specificity
  • Child
  • Child, Preschool
  • Complement C1q
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection
  • Graft Survival
  • HLA Antigens
  • Humans
  • Infant
  • Isoantibodies
  • Kidney Failure, Chronic
  • Kidney Function Tests
  • Kidney Transplantation
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Tissue Donors
  • Young Adult
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

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. / Nocera, A; Tagliamacco, A; Cioni, M; Innocente, A; Fontana, I; Barbano, G; Carrea, A; Ramondetta, M; Sementa, A; Basso, S; Quartuccio, G; Klersy, C; Bertocchi, M; Verrina, E; Garibotto, G; Ghiggeri, G M; Cardillo, M; Comoli, P; Ginevri, F.

In: American Journal of Transplantation, Vol. 17, No. 3, 03.2017, p. 692-702.

Research output: Contribution to journalArticle

Nocera, A, Tagliamacco, A, Cioni, M, Innocente, A, Fontana, I, Barbano, G, Carrea, A, Ramondetta, M, Sementa, A, Basso, S, Quartuccio, G, Klersy, C, Bertocchi, M, Verrina, E, Garibotto, G, Ghiggeri, GM, Cardillo, M, Comoli, P & Ginevri, F 2017, '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', American Journal of Transplantation, vol. 17, no. 3, pp. 692-702. https://doi.org/10.1111/ajt.14000
Nocera, A ; Tagliamacco, A ; Cioni, M ; Innocente, A ; Fontana, I ; Barbano, G ; Carrea, A ; Ramondetta, M ; Sementa, A ; Basso, S ; Quartuccio, G ; Klersy, C ; Bertocchi, M ; Verrina, E ; Garibotto, G ; Ghiggeri, G M ; Cardillo, M ; Comoli, P ; Ginevri, F. / 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. In: American Journal of Transplantation. 2017 ; Vol. 17, No. 3. pp. 692-702.
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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.",
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AU - Fontana, I

AU - Barbano, G

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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.

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