Identifying compartment-specific alloimmune targets after renal transplantation by integrating transcriptome and antibodyome measures.
Microarray technology has evolved as a powerful tool over the last decade, to identify biomarkers and study the mechanisms of diseases. We propose a novel application of integrated genomics by combining transcriptional levels with serological antibody profiling after kidney transplantation, with the aim of uncovering the relative immunogenicity of seven different renal compartments after allo-transplantation. Thirty-six paired pre- and post-transplant serum samples were examined from eighteen transplant recipients, across 5,056 protein targets on the ProtoArray V3.0 platform. Normal renal compartment-specific gene expression data from a cDNA platform were re-analyzed and both the cDNA and the ProtoArray platforms were re-annotated to most up-to-date NCBI gene identifiers; 3,835 genes/proteins are measured on both platforms. Antibody levels were ranked for individual patients and the hypergeometric enrichment statistic was applied on mapped compartment-specific expression data. We discovered that after transplantation, in addition to HLA and MICA responses, temporal alloimmune responses are seen against non-HLA antigens specific to different compartments of the kidney, with highest level responses noted against renal pelvis and cortex specific antigens. The renal medulla is of low immunogenicity as none of the outer or inner medulla specific targets generated significant post-transplant antibody responses. Immunohistochemistry confirmed pelvis and cortex specific localizations of selected targeted antigens, supporting the robust nature of this discovery. This study provides a road map of renal compartment-specific non-HLA antigenic targets responsible for generating alloimmune responses, opening the door for clinical correlations with post-transplant dysfunctional states to be determined.
http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10452
Li L, Wadia P, Chen R, Kambham N, Naesens M, Sigdel T, Miklos D, Sarwal MM, Butte AJ. Identifying compartment-specific alloimmune targets after renal transplantation by integrating transcriptome and antibodyome measures. Proc Natl Acad Sc U S A. 2009 Mar 17;106(11):4148-53.