Identifying compartment-specific non-HLA targets after renal transplantation by integrating transcriptome and “antibodyome” measures
Open Access
- 17 March 2009
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 106 (11), 4148-4153
- https://doi.org/10.1073/pnas.0900563106
Abstract
We have conducted an integrative genomics analysis of serological responses to non-HLA targets after renal transplantation, with the aim of identifying the tissue specificity and types of immunogenic non-HLA antigenic targets after transplantation. Posttransplant antibody responses were measured by paired comparative analysis of pretransplant and posttransplant serum samples from 18 pediatric renal transplant recipients, measured against 5,056 unique protein targets on the ProtoArray platform. The specificity of antibody responses were measured against gene expression levels specific to the kidney, and 2 other randomly selected organs (heart and pancreas), by integrated genomics, employing the mapping of transcription and ProtoArray platform measures, using AILUN. The likelihood of posttransplant non-HLA targets being recognized preferentially in any of 7 microdissected kidney compartments was also examined. In addition to HLA targets, non-HLA immune responses, including anti-MICA antibodies, were detected against kidney compartment-specific antigens, with highest posttransplant recognition for renal pelvis and cortex specific antigens. The compartment specificity of selected antibodies was confirmed by IHC. In conclusion, this study provides an immunogenic and anatomic roadmap of the most likely non-HLA antigens that can generate serological responses after renal transplantation. Correlation of the most significant non-HLA antibody responses with transplant health and dysfunction are currently underway.This publication has 44 references indexed in Scilit:
- AILUN: reannotating gene expression data automaticallyNature Methods, 2007
- Identification of differentially expressed proteins in ovarian cancer using high-density protein microarraysProceedings of the National Academy of Sciences of the United States of America, 2007
- Evaluation and integration of 49 genome-wide experiments and the prediction of previously unknown obesity-related genesBioinformatics, 2007
- NCBI GEO: mining tens of millions of expression profiles--database and tools updateNucleic Acids Research, 2006
- A gene atlas of the mouse and human protein-encoding transcriptomesProceedings of the National Academy of Sciences of the United States of America, 2004
- Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation1Transplantation, 2003
- Significance analysis of microarrays applied to the ionizing radiation responseProceedings of the National Academy of Sciences of the United States of America, 2001
- The Banff 97 working classification of renal allograft pathologyKidney International, 1999
- Autoimmune diseases: nuclear autoantigens can be found at the cell-surfaceMolecular Biology Reports, 1996
- Anatomy of the Human BodyThe American Journal of the Medical Sciences, 1919