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The clinical and genomic significance of donor-specific antibody-positive/C4d-negative and donor-specific antibody-negative/C4d-negative transplant glomerulopathy.
Hayde, Nicole; Bao, Yi; Pullman, James; Ye, Bin; Calder, R Brent; Chung, Monica; Schwartz, Daniel; Lubetzky, Michelle; Ajaimy, Maria; de Boccardo, Graciela; Akalin, Enver.
Afiliação
  • Hayde N; Division of Pediatric Nephrology,, †Montefiore-Einstein Center for Transplantation,, ‡Department of Pathology,, §Computational Genomics Facility, Department of Genetics, and, ‖Division of Nephrology, Albert Einstein College of Medicine, Bronx, New York.
Clin J Am Soc Nephrol ; 8(12): 2141-8, 2013 Dec.
Article em En | MEDLINE | ID: mdl-24030736
BACKGROUND: This study investigated the mechanisms involved in development of donor-specific antibody (DSA) and/or C4d-negative transplant glomerulopathy (TGP) by allograft gene expression profiles using microarrays. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This cohort study was conducted in kidney transplant recipients. Patients were eligible for inclusion if they required a clinically indicated biopsy at any time point after their transplant. They were then classified according to their histopathology findings and DSA and C4d results. Eighteen chronic antibody-mediated rejection (CAMR), 14 DSA+/C4d- TGP, 25 DSA-/C4d- TGP, and 47 nonspecific interstitial fibrosis/tubular atrophy (IFTA) biopsy specimens were identified. In a subset of patients from the study population, biopsy specimens in each group and normal transplant kidney specimens were analyzed with Affymetrix Human Gene 1.0 ST Arrays. RESULTS: The mean sum score of glomerulitis and peritubular capillaritis increased from 0.28±0.78 in IFTA specimens to 0.75±0.85 in DSA-/C4d- TGP specimens, 1.71±1.49 in DSA+/C4d-/TGP specimens, and 2.11±1.74 in CAMR specimens (P<0.001). During a median follow-up time of 2 (interquartile range, 1.4-2.8) years after biopsy, graft loss was highest in CAMR specimens (27.8%) compared to IFTA specimens (8.5%), DSA+/C4d- TGP specimens (14.3%), and DSA-/C4d- TGP specimens (16%) (P=0.01). With use of microarrays, comparison of the gene expression profiles of DSA-/C4d- TGP specimens with glomerulitis + peritubular capillaritis scores > 0 to normal and IFTA biopsy specimens revealed higher expression of quantitative cytotoxic T cell-associated transcripts (QCAT). However, both CAMR and DSA+/C4d- TGP specimens had higher expression of not only QCAT but also IFN-γ and rejection-induced, constitutive macrophage-associated, natural killer cell-associated, and DSA-selective transcripts. Endothelial cell-associated transcript expression was upregulated only in CAMR biopsy specimens. CONCLUSIONS: These results suggested that DSA+/C4d- TGP biopsy specimens may be classified as CAMR. In contrast, DSA-/C4d- TGP specimens showed increased cytotoxic T cell-associated transcripts, suggesting T cell activation as a mechanism of injury.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Complemento C4b / Transplante de Rim / Genômica / Glomerulonefrite / Rejeição de Enxerto / Histocompatibilidade / Isoanticorpos Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Complemento C4b / Transplante de Rim / Genômica / Glomerulonefrite / Rejeição de Enxerto / Histocompatibilidade / Isoanticorpos Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2013 Tipo de documento: Article