Antibody Mediated Rejection

Terasaki, Paul I.; Mizutani, Kazuo

doi:10.2215/cjn.02311205

Cited by 42 publications

(26 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…plasma; (2) inflammation in the allograft microcirculation: peritubular capillaritis (ptc) and glomerulitis (g); (3) evidence of antibody interaction with vascular endothelium, as attested to by C4d deposits on the endothelial cells of peritubular capillaries (PTC), or of moderate microvascular inflammation, or of elevated endothelial injury-activated gene transcripts. As a marker, C4d is not sensitive, however.…”

mentioning

confidence: 99%

“…18,19 The aim of our work was to test the hypothesis that expression of EndMT markers could serve as evidence of current endothelial reaction following DSA binding and/or complement activation and thus help to consolidate the diagnosis of ABMR in renal grafts. Among the potential endothelial activation indicators analyzed, we studied particularly the expression of three mesenchymal markers: (1) fascin1, an actin-bundling protein involved in cell motility; (2) vimentin, an intermediate filament; and (3) hsp47, a collagen-specific chaperone protein, in endothelial cells from PTC of renal grafts with and without ABMR. Our study reveals that EndMT markers accurately diagnose ABMR and predict long-term graft dysfunction.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Markers of Endothelial-to-Mesenchymal Transition

Xu‐Dubois

Peltier

Brochériou

et al. 2016

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Antibody-mediated rejection (ABMR) is a leading cause of allograft loss. Treatment efficacy depends on accurate diagnosis at an early stage. However, sensitive and reliable markers of antibody-endothelium interaction during ABMR are not available for routine use. Using immunohistochemistry, we retrospectively studied the diagnostic value of three markers of endothelial-to-mesenchymal transition (EndMT), fascin1, vimentin, and heat shock protein 47, for ABMR in 53 renal transplant biopsy specimens, including 20 ABMR specimens, 24 cell-mediated rejection specimens, and nine normal grafts. We validated our results in an independent set of 74 unselected biopsy specimens. Endothelial cells of the peritubular capillaries in grafts with ABMR expressed fascin1, vimentin, and heat shock protein 47 strongly, whereas those from normal renal grafts did not. The level of EndMT marker expression was significantly associated with current ABMR criteria, including capillaritis, glomerulitis, peritubular capillary C4d deposition, and donor-specific antibodies. These markers allowed us to identify C4d-negative ABMR and to predict late occurrence of disease. EndMT markers were more specific than capillaritis for the diagnosis and prognosis of ABMR and predicted late (up to 4 years after biopsy) renal graft dysfunction and proteinuria. In the independent set of 74 renal graft biopsy specimens, the EndMT markers for the diagnosis of ABMR had a sensitivity of 100% and a specificity of 85%. Fascin1 expression in peritubular capillaries was also induced in a rat model of ABMR. In conclusion, EndMT markers are a sensitive and reliable diagnostic tool for detecting endothelial activation during ABMR and predicting late loss of allograft function.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Markers of Endothelial-to-Mesenchymal Transition

Xu‐Dubois

Peltier

Brochériou

et al. 2016

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…This may relate to the heterogeneity of the acute rejection injury (2) (3), but there is extensive evidence that antibodies recognizing and engaging with donor antigens also play a key role in renal allograft outcomes (4).…”

mentioning

confidence: 99%

Identifying compartment-specific non-HLA targets after renal transplantation by integrating transcriptome and “antibodyome” measures

Li¹,

Wadia²,

Chen

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

141

View full text Add to dashboard Cite

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.integrative genomics ͉ kidney compartment ͉ kidney transplantation ͉ non-HLA antigen

show abstract

“…The detrimental effect of HLA Class II -antibodies directed against allograft antigens on transplantation outcome is well established [10][11][12]. The significance of the DQ antibodies is increasingly recognized following the introduction of the SAB assay which considered today to be the most sensitive and specific method for alloimmunization assessment [13][14][15].…”

Section: Discussionmentioning

confidence: 99%