Non-HLA antibodies to immunogenic epitopes predict the evolution of chronic renal allograft injury.
Chronic allograft injury (CAI) results from a humoral response to mismatches in immunogenic epitopes between the donor and recipient. Although alloantibodies against HLA antigens contribute to the pathogenesis of CAI, alloantibodies against non-HLA antigens likely contribute as well. Here, we used high-density protein arrays to identify non-HLA antibodies in CAI and subsequently validated a subset in a cohort of 172 serum samples collected serially post-transplantation. There were 38 de novo non-HLA antibodies that significantly associated with the development of CAI (P<0.01) on protocol post-transplant biopsies, with enrichment of their corresponding antigens in the renal cortex. Baseline levels of preformed antibodies to MIG (also called CXCL9), ITAC (also called CXCL11), IFN-γ, and glial-derived neurotrophic factor positively correlated with histologic injury at 24 months. Measuring levels of these four antibodies could help clinicians predict the development of CAI with >80% sensitivity and 100% specificity. In conclusion, pretransplant serum levels of a defined panel of alloantibodies targeting non-HLA immunogenic antigens associate with histologic CAI in the post-transplant period. Validation in a larger, prospective transplant cohort may lead to a noninvasive method to predict and monitor for CAI.
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5208, USA.
Tara K
TK
Sigdel
Li
L
Li
Tim Q
TQ
Tran
Purvesh
P
Khatri
Maarten
M
Naesens
Poonam
P
Sansanwal
Hong
H
Dai
Szu-chuan
SC
Hsieh
Minnie M
MM
Sarwal
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000917:Antibody Formation / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001707:Biopsy, Needle; D002908:Chronic Disease; D015331:Cohort Studies; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007518:Isoantibodies / Q000097:blood*; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
D015415:Biomarkers; D000939:Epitopes; D006680:HLA Antigens; D007518:Isoantibodies