Non-HLA antibodies to immunogenic epitopes predict the evolution of chronic renal allograft injury

Tara K. Sigdel, Li Li, Tim Q. Tran, Purvesh Khatri, Maarten Naesens, Poonam Sansanwal, Hong Dai, Szu Chuan Hsieh, Minnie M. Sarwal

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

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 highdensity 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.

Original languageEnglish
Pages (from-to)750-763
Number of pages14
JournalJournal of the American Society of Nephrology : JASN
Volume23
Issue number4
DOIs
StatePublished - Apr 2012
Externally publishedYes

Fingerprint

Dive into the research topics of 'Non-HLA antibodies to immunogenic epitopes predict the evolution of chronic renal allograft injury'. Together they form a unique fingerprint.

Cite this