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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
Author(s) -
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.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14000
Subject(s) - medicine , biopsy , donor specific antibodies , kidney transplantation , transplantation , kidney , homing (biology) , antibody , pathology , human leukocyte antigen , isoantibodies , immunology , antigen , surgery , biology , ecology
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 ( dn DSA ) 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 dn DSA s with flow bead technology. Intragraft dn DSA s ( gDSA s) were never detected in the absence of serum dn DSA s ( sDSA s), whereas in the presence of sDSA s, gDSA s were demonstrated in 72% of biopsy specimens. A significantly higher homing capability was expressed by class II sDSA s endowed with high mean fluorescence intensity and C3d‐ and/or C1q‐fixing properties. In patients with available sequential biopsy specimens, we detected gDSA s 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 gDSA s could represent an instrumental tool to identify, among sDSA s, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management.