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 language | English |
|---|---|
| Pages (from-to) | 692-702 |
| Journal | American Journal of Transplantation |
| Volume | 17 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2017 |
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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
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, Giancarlo; Carrea, Alba Maria; Ramondetta, Miriam; Sementa, Angela Rita; Basso, Sabrina; Quartuccio, Giuseppe; Klersy, Catherine; Bertocchi, M.; Verrina, Enrico; Garibotto, G.; Ghiggeri, Gian Marco; Cardillo, Massimo; Comoli, Patrizia; Ginevri, F.
In: American Journal of Transplantation, Vol. 17, No. 3, 2017, p. 692-702.Research output: Contribution to journal › Article
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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)
UR - http://www.scopus.com/inward/record.url?scp=84987630036&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84987630036&partnerID=8YFLogxK
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 -