TY - JOUR
T1 - Antibody-mediated allograft rejection
T2 - Morphologic spectrum and serologic correlations in surveillance and for cause biopsies
AU - Papadimitriou, John C.
AU - Drachenberg, Cinthia B.
AU - Ramos, Emilio
AU - Kukuruga, Debra
AU - Klassen, David K.
AU - Ugarte, Richard
AU - Nogueira, Joseph
AU - Cangro, Charles
AU - Weir, Matthew R.
AU - Haririan, Abdolreza
PY - 2013/1/15
Y1 - 2013/1/15
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.
AB - 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.
KW - Banff grading schema
KW - C4d
KW - CD68
KW - Capillaritis
KW - Donor-specific antibody
KW - Endothelial injury
KW - Glomerular macrophages
KW - Glomerulitis
KW - HLA class I
KW - HLA class II
KW - Mean fluorescence index
KW - Microvascular inflammation
KW - Transplant glomerulopathy
UR - http://www.scopus.com/inward/record.url?scp=84872064806&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872064806&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e3182777f28
DO - 10.1097/TP.0b013e3182777f28
M3 - Article
C2 - 23222897
AN - SCOPUS:84872064806
SN - 0041-1337
VL - 95
SP - 128
EP - 136
JO - Transplantation
JF - Transplantation
IS - 1
ER -