Specificity and sensitivity of screening for anti-HLA antibodies in kidney allograft dysfunction.
BACKGROUND
Prospective testing for posttransplant circulating anti-HLA antibodies seems to be a critical noninvasive tool, but confirmatory data are lacking.


METHODS
Over the last 3 years, peritubular capillary (PTC) C4d deposition was prospectively sought by an immunofluorescence technique applied to frozen tissue in biopsies obtained for allograft dysfunction. Screening for circulating anti-HLA class I/II alloantibodies (AlloAb) by the flow cytometric test was performed simultaneously.


RESULTS
We evaluated 132 sets of biopsies and simultaneous serum samples. PTC C4d deposition was demonstrated in 15.9% (21/132) of biopsies. Circulating anti-HLA I/II AlloAb were detected in 25% (33/132) of serum samples. Employing receiver-operator characteristic (ROC) curves for all C4d-positive biopsies, screening for AlloAb showed a global specificity of 82% and sensitivity of 61.9%. When this analysis was restricted to biopsies obtained in the first month posttransplantation, the sensitivity increased to 81.8%, but the specificity decreased to 76.9%. After the first month posttransplantation, we observed sensitivity of 40.0% and a specificity of 86.4%. In the first month posttransplantation, all patients with a diagnosis of acute antibody-mediated rejection displayed circulating anti-HLA class I/II, but not always at the same time as the C4d-positive biopsy.


CONCLUSIONS
In the first month posttransplantation, prospective monitoring of anti-HLA antibodies may be useful. The high sensitivity allows the identification of patients at risk, affording an earlier diagnosis of antibody-mediated rejection. After the first month, the test can be used to evaluate allograft dysfunction episodes, since positivity is highly suggestive of an antibody-mediated process.
Viana
H
H
Hospital Curry Cabral, Servico de Nefrologia, Lisboa, Portugal. Viana.helena@gmail.com
Nolasco
F
F
Santos
M C
MC
Carvalho
F
F
Galvão
M J
MJ
Santos
A R
AR
Bordalo
J
J
Dos Santos
J R
JR
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015935:Complement C4b / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D012086:Reoperation / Q000706:statistics & numerical data; D012680:Sensitivity and Specificity; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology*
D015415:Biomarkers; D006680:HLA Antigens; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d