title: Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes.
abstract: The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy.
authors: Division of Nephrology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
authors: Maarten
authors: M
authors: Naesens
authors: Purvesh
authors: P
authors: Khatri
authors: Li
authors: L
authors: Li
authors: Tara K
authors: TK
authors: Sigdel
authors: Matthew J
authors: MJ
authors: Vitalone
authors: Rong
authors: R
authors: Chen
authors: Atul J
authors: AJ
authors: Butte
authors: Oscar
authors: O
authors: Salvatierra
authors: Minnie M
authors: MM
authors: Sarwal
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002140:California; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents