Early and Late Humoral Rejection: A Clinicopathologic Entity in Two Times

Pefaur, Jacqueline; Díaz, Pablo; Panace, Rita; Salinas, Pedro; Fiabane, A; Quinteros, N.; Chea, R.; Naranjo, E.; Wurgaft, A.; Beltrán, Eduardo; Elgueta, Susana; Wegmann, Marlene; Gajardo, J.G.; Contreras, Luis

doi:10.1016/j.transproceed.2008.03.123

Cited by 20 publications

(14 citation statements)

References 90 publications

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“…Bortezomib was well tolerated in our patients. The sole patient with early AMR in our cohort had dramatic recovery with the use of bortezomib as rescue therapy, consistent with previous studies [19, 20, 29]. This included resolution of DSAs, improvement in biopsy findings, and recovery of renal function.…”

Section: Discussionsupporting

confidence: 89%

Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection

et al. 2016

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Background Current therapeutic strategies to effectively treat antibody-mediated rejection (AMR) are insufficient. Thus, we aimed to determine the benefit of a therapeutic protocol using bortezomib for refractory C4d+ AMR in pediatric kidney transplant patients. Methods We examined 7 patients with treatment refractory C4d+ AMR. Immunosuppression included antithymocyte globulin or anti-CD25 monoclonal antibody for induction therapy with maintenance corticosteroids, calcineurin inhibitor, and antimetabolite. Estimated glomerular filtration rate (eGFR) calculated by the Schwartz equation, biopsy findings assessed by 2013 Banff criteria, and human leukocyte antigen (HLA) donor specific antibodies (DSA) performed using the Luminex single antigen bead assay were monitored pre- and post- bortezomib therapy. Results Seven patients (86% male, 86% with ≥6/8 HLA mismatch, and 14% with pre-formed DSA) age 5 to 19 (median 15) years developed refractory C4d + AMR between 1–145 (median 65) months post-transplantation. All patients tolerated bortezomib. One patient had allograft loss. Of the six patients with surviving grafts (86%), the mean pre-bortezomib eGFR was 42 mls/min/1.73 m2 and the mean 1 year post-bortezomib eGFR was 53 mls/min/1.73m2. Five of 7 (71%) had improvement of histological findings of AMR, C4d staining, and/or acute cellular rejection. Reduction in HLA DSAs was more effective for Class I than Class II. Conclusions Bortezomib appears safe and may correlate with stabilization of eGFR in pediatric kidney transplant patients with refractory C4d+ AMR.

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Section: Discussionsupporting

confidence: 89%

Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection

et al. 2016

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“…Cellular immunity includes T-cell-mediated cytotoxicity and also natural killer cell-mediated and macrophagemediated cytotoxicity [17][18][19]. Humoral immunity attacks allografts by producing specific antibodies against the grafts [20][21][22][23][24]. In addition, pre-existing conditions, such as diabetes mellitus, [25,26], hypertension [27,28], cardiovascular conditions [29,30], infections [31][32][33], malignancy [34][35][36], were all factors that affect the outcomes and survival of transplant grafts.…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of renal allograft rejection in serum using magnetic bead–based sample fractionation and MALDI-TOF MS

et al. 2010

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Proteomics is one of the emerging techniques for biomarker discovery. Biomarkers can be used for early noninvasive diagnosis and prognosis of diseases and treatment efficacy evaluation. In the present study, the well-established research systems of ClinProt Micro solution incorporated unique magnetic bead sample preparation technology, which, based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), have become very successful in bioinformatics due to its outstanding performance and reproducibility for discovery disease-related biomarker. We collected fasting blood samples from patients with biopsy-confirmed acute renal allograft rejection (n = 12), chronic rejection (n = 12), stable graft function (n = 12) and also from healthy volunteers (n = 13) to study serum peptidome patterns. Specimens were purified with magnetic bead-based weak cation exchange chromatography and analyzed with a MALDI-TOF mass spectrometer. The results indicated that 18 differential peptide peaks were selected as potential biomarkers of acute renal allograft rejection, and 6 differential peptide peaks were selected as potential biomarkers of chronic rejection. A Quick Classifier Algorithm was used to set up the classification models for acute and chronic renal allograft rejection. The algorithm models recognize 82.64% of acute rejection and 98.96% of chronic rejection episodes, respectively. We were able to identify serum protein fingerprints in small sample sizes of recipients with renal allograft rejection and establish the models for diagnosis of renal allograft rejection. This preliminary study demonstrated that proteomics is an emerging tool for early diagnosis of renal allograft rejection and helps us to better understand the pathogenesis of disease process.

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“…The prognostic value of this hallmark is confirmed for early rejection episodes [10,11] however it is not generally accepted as a negative prognostic factor in the late acute and chronic transplant rejection. Even though several studies showed that renal graft survival in C4d-positive late AMR was significantly lower compared to C4d-negative cases [19][20][21][22], other authors did not confirm this association [23][24][25]. Keiran et al, who studied the renal graft biopsies performed late (>10 years) after transplantation, demonstrated prognostic value of C4d expression only in its association with TG, while in the absence of the latter C4d-positivity did not influence the prognosis [26].…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Value of Late Kidney Transplant Rejection Pathology Characteristics

Stolyarevich¹,

Artyukhina²,

Zakharova³

et al. 2016

J Transplant Technol Res

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Renal allograft rejection, represented by the wide spectrum of lesions with different pathogenesis, pathology patterns, clinical course and prognosis, still remains the most often cause of late graft dysfunction. Moreover, a combination of several factors, either of which may impact the post-transplant course, generally take place. We aimed to analyze the incidence of late renal allograft rejection variants, and to determine clinical factors and pathology features, influencing prognosis in the specific types of late renal allograft rejection.The data obtained from 361 patients with acute (n=227) or chronic (n=134) late allograft rejection (mean time after kidney transplantation 48.8 ± 46.1 months) were analyzed retrospectively. C4d expression was found in 34% cases of acute rejection and in 58% cases of chronic rejection (64% in chronic transplant glomerulopathy and 52% in transplant vasculopathy). 5-year graft survival comprised 48% and 24% for acute and chronic transplant rejection respectively (Р<0.01). Combination of acute cell-mediated rejection with chronic transplant rejection did not influence significantly the prognosis for the latter. Diffuse C4d expression on peritubular capillaries turned to be an independent prognostic factor regardless the pathology variant of renal allograft rejection. In contrast, focal C4d expression had no impact on the prognosis, which did not differ significantly from C4d-negative type. On the other hand, in acute rejection prognosis for C4d-positive forms was worse compared to C4d-negative (55% vs 25%; P <0.01), while in chronic rejection there was no difference between C4d-positive and C4d-negative forms (26% vs 24%; P=NS). In multivariate Cox-model analysis, the following factors appeared to influence the prognosis: presence of chronic transplant glomerulopathy, features of vasculitis, severity of tubulitis, presence of thrombotic micrioangiopathy and prominence of interstitial fibrosis.

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Early and Late Humoral Rejection: A Clinicopathologic Entity in Two Times

Cited by 20 publications

References 90 publications

Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection

Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection

Proteomic profiling of renal allograft rejection in serum using magnetic bead–based sample fractionation and MALDI-TOF MS

The Prognostic Value of Late Kidney Transplant Rejection Pathology Characteristics

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