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1.
Front Immunol ; 13: 839380, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493469

RESUMO

Introduction: Chronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other complications. Kidney transplantation is a renal-replacement therapy that offers better survival compared to dialysis. Antibody-mediated rejection (ABMR) is a significant complication following kidney transplantation: it contributes to both short- and long-term injury. The standard-of-care (SOC) therapy combines plasmapheresis and Intravenous Immunoglobulins (IVIg) with or without steroids, with or without rituximab: however, despite this combined treatment, ABMR remains the main cause of graft loss. IL-6 is a key cytokine: it regulates inflammation, and the development, maturation, and activation of T cells, B cells, and plasma cells. Tocilizumab (TCZ) is the main humanized monoclonal aimed at IL-6R and appears to be a safe and possible strategy to manage ABMR in sensitized recipients. We conducted a literature review to assess the place of the anti-IL-6R monoclonal antibody TCZ within ABMR protocols. Materials and Methods: We systematically reviewed the PubMed literature and reviewed six studies that included 117 patients and collected data on the utilization of TCZ to treat ABMR. Results: Most studies report a significant reduction in levels of Donor Specific Antibodies (DSAs) and reduced inflammation and microvascular lesions (as found in biopsies). Stabilization of the renal function was observed. Adverse events were light to moderate, and mortality was not linked with TCZ treatment. The main side effect noted was infection, but infections did not occur more frequently in patients receiving TCZ as compared to those receiving SOC therapy. Conclusion: TCZ may be an alternative to SOC for ABMR kidney-transplant patients, either as a first-line treatment or after failure of SOC. Further randomized and controlled studies are needed to support these results.


Assuntos
Transplante de Rim , Anticorpos Monoclonais Humanizados , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Antígenos HLA , Humanos , Inflamação/etiologia , Isoanticorpos , Transplante de Rim/efeitos adversos , Masculino
2.
Transpl Int ; 35: 10128, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35516975

RESUMO

In HLA-incompatible kidney transplantation, monitoring donor-specific antibodies (DSA) plays a crucial role in providing appropriate treatment and increases kidney survival times. This work aimed to determine if early post-transplant DSA dynamics inform graft outcome over and above other predictive factors. Eighty-eight cases were classified by unsupervised machine learning into five distinct DSA response groups: no response, fast modulation, slow modulation, rise to sustained and sustained. Fast modulation dynamics gave an 80% rate for early acute rejection, whereas the sustained group was associated with the lowest rejection rates (19%). In complete contrast, the five-year graft failure was lowest in the modulation groups (4-7%) and highest in the sustained groups (25-31%). Multivariable analysis showed that a higher pre-treatment DSA level, male gender and absence of early acute rejection were strongly associated with a sustained DSA response. The modulation group had excellent five-year outcomes despite higher rates of early rejection episodes. This work further develops an understanding of post-transplant DSA dynamics and their influence on graft survival following HLA-incompatible kidney transplantation.


Assuntos
Transplante de Rim , Anticorpos , Rejeição de Enxerto , Sobrevivência de Enxerto , Antígenos HLA , Humanos , Isoanticorpos , Masculino , Estudos Retrospectivos , Doadores de Tecidos
3.
Transpl Int ; 35: 10279, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35368637

RESUMO

The association between blood transfusion and the occurrence of de novo HLA donor specific antibodies (DSA) after kidney transplantation remains controversial. In this single-center observational study, we examined the association between early blood transfusion, i.e. before 1-month post-transplantation, and the risk of DSA occurrence, using Luminex based-methods. In total, 1,424 patients with a minimum of 1-month follow-up were evaluated between January 2007 and December 2018. During a median time of follow-up of 4.52 years, we observed 258 recipients who had at least one blood transfusion during the first month post-transplantation. At baseline, recipients in the transfused group were significant older, more sensitized against HLA class I and class II antibodies and had a higher 1-month serum creatinine. Cox proportional hazards regression analyses did not show any significant association between blood transfusion and the risk of de novo DSA occurrence (1.35 [0.86-2.11], p = 0.19), the risk of rejection (HR = 1.33 [0.94-1.89], p = 0.11), or the risk of graft loss (HR = 1.04 [0.73-1.50], p = 0.82). These data suggest then that blood transfusion may not be limited when required in the early phase of transplantation, and may not impact long-term outcomes.


Assuntos
Rejeição de Enxerto , Isoanticorpos , Aloenxertos , Transfusão de Sangue , Sobrevivência de Enxerto , Antígenos HLA , Humanos , Rim , Estudos Retrospectivos
4.
Transfusion ; 62(5): 948-953, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35470900

RESUMO

BACKGROUND: Alloimmunization can be a significant barrier to red blood cell (RBC) transfusion. While alloantigen matching protocols hold promise in reducing alloantibody formation, transfusion-dependent patients can still experience RBC alloimmunization and associated complications even when matching protocols are employed. As a result, complementary strategies capable of actively preventing alloantibody formation following alloantigen exposure are warranted. STUDY DESIGN AND METHODS: We examined whether pharmacological removal of macrophages using clodronate may provide an additional strategy to actively inhibit RBC alloimmunization using two preclinical models of RBC alloimmunization. To accomplish this, mice were treated with clodronate, followed by transfusion of RBCs expressing the HOD (HEL, OVA, and Duffy) or KEL antigens. On days 5 and 14 post transfusion, anti-HOD or anti-KEL IgM and IgG antibodies were evaluated. RESULTS: Low dose clodronate effectively eliminated key marginal zone macrophage populations from the marginal sinus. Prior treatment with clodronate, but not empty liposomes, also significantly inhibited IgM and IgG anti-HOD alloantibody formation following transfusion of HOD RBCs. Similar exposure to clodronate inhibited IgM and IgG antibody formation following KEL RBC transfusion. CONCLUSIONS: Clodronate can inhibit anti-HOD and anti-KEL antibody formation following RBC transfusion in preclinical models. These results suggest that clodronate may provide an alternative approach to actively inhibit or prevent the development of alloantibodies following RBC transfusion, although future studies will certainly be needed to fully explore this possibility.


Assuntos
Ácido Clodrônico , Isoantígenos , Animais , Ácido Clodrônico/farmacologia , Eritrócitos , Humanos , Imunoglobulina G , Imunoglobulina M , Isoanticorpos , Camundongos
7.
Front Immunol ; 13: 829228, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401541

RESUMO

Natural killer (NK) cells may contribute to antibody-mediated rejection (ABMR) of renal allografts. The role of distinct NK cell subsets in this specific context, such as NK cells expressing the activating receptor NKG2C, is unknown. Our aim was to investigate whether KLRC2 gene deletion variants which determine NKG2C expression affect the pathogenicity of donor-specific antibodies (DSA) and, if so, influence long-term graft survival. We genotyped the KLRC2 wt/del variants for two distinct kidney transplant cohorts, (i) a cross-sectional cohort of 86 recipients who, on the basis of a positive post-transplant DSA result, all underwent allograft biopsies, and (ii) 1,860 recipients of a deceased donor renal allograft randomly selected from the Collaborative Transplant Study (CTS) database. In the DSA+ patient cohort, KLRC2 wt/wt (80%) was associated with antibody-mediated rejection (ABMR; 65% versus 29% among KLRC2 wt/del subjects; P=0.012), microvascular inflammation [MVI; median g+ptc score: 2 (interquartile range: 0-4) versus 0 (0-1), P=0.002], a molecular classifier of ABMR [0.41 (0.14-0.72) versus 0.10 (0.07-0.27), P=0.001], and elevated NK cell-related transcripts (P=0.017). In combined analyses of KLRC2 variants and a functional polymorphism in the Fc gamma receptor IIIA gene (FCGR3A-V/F158), ABMR rates and activity gradually increased with the number of risk genotypes. In DSA+ and CTS cohorts, however, the KLRC2 wt/wt variant did not impact long-term death-censored graft survival, also when combined with the FCGR3A-V158 risk variant. KLRC2 wt/wt may be associated with DSA-triggered MVI and ABMR-associated gene expression patterns, but the findings observed in a highly selected cohort of DSA+ patients did not translate into meaningful graft survival differences in a large multicenter kidney transplant cohort not selected for HLA sensitization.


Assuntos
Transplante de Rim , Estudos Transversais , Rejeição de Enxerto , Humanos , Isoanticorpos , Transplante de Rim/efeitos adversos , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília D de Receptores Semelhantes a Lectina de Células NK , Receptores de Células Matadoras Naturais
8.
Trials ; 23(1): 270, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35395951

RESUMO

BACKGROUND: Antibody-mediated rejection (ABMR) is a cardinal cause of renal allograft loss. This rejection type, which may occur at any time after transplantation, commonly presents as a continuum of microvascular inflammation (MVI) culminating in chronic tissue injury. While the clinical relevance of ABMR is well recognized, its treatment, particularly a long time after transplantation, has remained a big challenge. A promising strategy to counteract ABMR may be the use of CD38-directed treatment to deplete alloantibody-producing plasma cells (PC) and natural killer (NK) cells. METHODS: This investigator-initiated trial is planned as a randomized, placebo-controlled, double-blind, parallel-group, multi-center phase 2 trial designed to assess the safety and tolerability (primary endpoint), pharmacokinetics, immunogenicity, and efficacy of the fully human CD38 monoclonal antibody felzartamab (MOR202) in late ABMR. The trial will include 20 anti-HLA donor-specific antibody (DSA)-positive renal allograft recipients diagnosed with active or chronic active ABMR ≥ 180 days post-transplantation. Subjects will be randomized 1:1 to receive felzartamab (16 mg/kg per infusion) or placebo for a period of 6 months (intravenous administration on day 0, and after 1, 2, 3, 4, 8, 12, 16, and 20 weeks). Two follow-up allograft biopsies will be performed at weeks 24 and 52. Secondary endpoints (preliminary assessment) will include morphologic and molecular rejection activity in renal biopsies, immunologic biomarkers in the blood and urine, and surrogate parameters predicting the progression to allograft failure (slope of renal function; iBOX prediction score). DISCUSSION: Based on the hypothesis that felzartamab is able to halt the progression of ABMR via targeting antibody-producing PC and NK cells, we believe that our trial could potentially provide the first proof of concept of a new treatment in ABMR based on a prospective randomized clinical trial. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT) 2021-000545-40 . Registered on 23 June 2021. CLINICALTRIALS: gov NCT05021484 . Registered on 25 August 2021.


Assuntos
Anticorpos Monoclonais Humanizados , Rejeição de Enxerto , Transplante de Rim , Aloenxertos , Anticorpos Monoclonais Humanizados/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/prevenção & controle , Humanos , Isoanticorpos , Rim/patologia , Rim/fisiologia , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Front Immunol ; 13: 838985, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281011

RESUMO

Introduction: Studies have shown reduced antiviral responses in kidney transplant recipients (KTRs) following SARS-CoV-2 mRNA vaccination, but data on post-vaccination alloimmune responses and antiviral responses against the Delta (B.1.617.2) variant are limited. Materials and methods: To address this issue, we conducted a prospective, multi-center study of 58 adult KTRs receiving mRNA-BNT162b2 or mRNA-1273 vaccines. We used multiple complementary non-invasive biomarkers for rejection monitoring including serum creatinine, proteinuria, donor-derived cell-free DNA, peripheral blood gene expression profile (PBGEP), urinary CXCL9 mRNA and de novo donor-specific antibodies (DSA). Secondary outcomes included development of anti-viral immune responses against the wild-type and Delta variant of SARS-CoV-2. Results: At a median of 85 days, no KTRs developed de novo DSAs and only one patient developed acute rejection following recent conversion to belatacept, which was associated with increased creatinine and urinary CXCL9 levels. During follow-up, there were no significant changes in proteinuria, donor-derived cell-free DNA levels or PBGEP. 36% of KTRs in our cohort developed anti-wild-type spike antibodies, 75% and 55% of whom had neutralizing responses against wild-type and Delta variants respectively. A cellular response against wild-type S1, measured by interferon-γ-ELISpot assay, developed in 38% of KTRs. Cellular responses did not differ in KTRs with or without antibody responses. Conclusions: SARS-CoV-2 mRNA vaccination in KTRs did not elicit a significant alloimmune response. About half of KTRs who develop anti-wild-type spike antibodies after two mRNA vaccine doses have neutralizing responses against the Delta variant. There was no association between anti-viral humoral and cellular responses.


Assuntos
/imunologia , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Monitorização Fisiológica/métodos , SARS-CoV-2/imunologia , Idoso , Anticorpos Antivirais/sangue , ELISPOT , Feminino , Humanos , Imunidade Celular , Isoanticorpos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo , Vacinação
11.
Transfusion ; 62(5): 1084-1088, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35318689

RESUMO

INTRODUCTION: Exposure to normal or variably expressed RhD antigens in an antigen-negative individual can elicit an immune response and lead to the formation of clinically significant anti-D alloantibodies. We present the case of anti-D alloimmunization by DEL variant missed in routine blood donor screening. MATERIAL AND METHODS: Blood donors were typed for D antigen using the direct serologic micromethod. Nonreactive samples were confirmed in the indirect antiglobulin method with an IgM/IgG anti-D monoclonal reagent. Genomic DNA was extracted using a commercial QIAamp DNA Blood Mini kit on the QIAcube device (Qiaqen, Germany). RHD genotyping was performed using the PCR-SSP genotyping kits- Ready Gene D weak, Ready Gene D weak screen, Ready Gene CDE, and Ready Gene D AddOn (Inno-Train, Germany). Unidentified alleles were sent for DNA genome sequencing. RESULTS: After identifying DEL positive blood units in RhD negative blood donor pool, a look-back study was performed to determine if their previous donations caused alloimmunization in recipients. Out of 40 D negative recipients, one developed anti-D alloantibody after 45 days. The patient did not receive other RhD positive blood products. Blood donor typed D negative in direct and indirect agglutination method. RHD screening was positive, but RHD genotyping and DNA sequencing showed no mutation indicating the normal genotype. CONCLUSION: Currently used methods in RHD genotyping are insufficient to identify many variant alleles, especially intronic variations. We suggest additional gene investigation including yet unexplored regions of regulation and intron regions to justify our serological finding.


Assuntos
Antígenos de Grupos Sanguíneos , Sistema do Grupo Sanguíneo Rh-Hr , Alelos , Doadores de Sangue , DNA , Genótipo , Humanos , Isoanticorpos , Fenótipo , Sistema do Grupo Sanguíneo Rh-Hr/genética
12.
Pediatr Transplant ; 26(4): e14251, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35279919

RESUMO

BACKGROUND: Our knowledge of de novo anti-HLA donor-specific antibodies (dnDSA) in liver transplantation continues to be defined. We hypothesized that differences of HLA-DR/DQ mismatches can improve precision in alloimmune risk categorization and be applied to tailor immunosuppression. METHODS: A retrospective chart review of 244 pediatric patients consecutively transplanted at our center between 2003 and 2019 was performed to identify patients tested for dnDSA. Records were queried for: demographics, pre-transplant diagnosis, biopsy-proven T-cell-mediated rejection (TCMR), radiology proven biliary complications, tacrolimus trough levels, dnDSA characteristics, and HLA typing. The eplet mismatch analyses were performed using HLAMatchmaker™ 3.1. All statistical analyses were conducted using R software version 3.40. RESULTS: There were 99 dnDSA-negative patients and 73 dnDSA-positive patients (n = 70 against class II and n = 3 against class I and II). ROC analysis identified optimal cutoff of eplet mismatch load for dnDSA and defined risk groups for an alloimmune outcome. Kaplan-Meier curves and log-rank tests showed high eplet mismatch load was associated with shorter dnDSA-free survival (log-rank p = .001). Multivariable Cox regression models showed that tacrolimus coefficient of variation and tacrolimus mean levels were significantly associated with dnDSA-free survival (p < .001 and p = .036). Fisher's exact test showed that dnDSA was associated with an increased likelihood of TCMR (OR 14.94; 95% CI 3.65 - 61.19; p < .001). Patients without TCMR were more likely to have dnDSA to HLA-DQ7 and less likely to have dnDSA to HLA-DQ2 (p = .03, p = .080). CONCLUSIONS: Mismatched epitope load predicts dnDSA-free survival in pediatric liver transplant, while dnDSA specificity may determine alloimmune outcome.


Assuntos
Transplante de Rim , Transplante de Fígado , Criança , Epitopos , Rejeição de Enxerto , Sobrevivência de Enxerto , Antígenos HLA , Teste de Histocompatibilidade , Humanos , Isoanticorpos , Estudos Retrospectivos , Tacrolimo/uso terapêutico
13.
Front Immunol ; 13: 809059, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250981

RESUMO

BACKGROUND: Many kidney allografts fail due to the occurrence of antibody-mediated rejection (ABMR), related to donor-specific anti-HLA antibodies (HLA-DSA). However, the histology of ABMR can also be observed in patients without HLA-DSA. While some non-HLA antibodies have been related to the histology of ABMR, it is not well known to what extent they contribute to kidney allograft injury. Here we aimed to investigate the role of 82 different non-HLA antibodies in the occurrence of histology of ABMR after kidney transplantation. METHODS: We included all patients who underwent kidney transplantation between 2004-2013 in a single center and had biobanked serum. Pre- and post-transplant sera (n=2870) were retrospectively tested for the presence of 82 different non-HLA antibodies using a prototype bead assay on Luminex (Immucor, Inc). A ratio was calculated between the measured MFI value and the cut-off MFI defined by the vendor for each non-HLA target. RESULTS: 874 patients had available pretransplant sera and were included in this analysis. Of them, 133 (15.2%) received a repeat kidney allograft, and 100 (11.4%) had pretransplant HLA-DSA. In total, 204 (23.3%) patients developed histology of ABMR after kidney transplantation. In 79 patients (38.7%) the histology of ABMR was explained by pretransplant or de novo HLA-DSA. The multivariable Cox analysis revealed that only the broadly non-HLA sensitized (number of positive non-HLA antibodies) patients and those with the highest total strength of the non-HLA antibodies (total ratios of the positive non-HLA antibodies) were independently associated with increased rates of histology of ABMR after transplantation. Additionally, independent associations were found for antibodies against TUBB (HR=2.40; 95% CI 1.37 - 4.21, p=0.002), Collagen III (HR=1.67; 95% CI 1.08 - 2.58, p=0.02), VCL (HR=2.04; 95% CI 1.12 - 3.71, p=0.02) and STAT6 (HR=1.47; 95% CI 1.01 - 2.15, p=0.04). The overall posttransplant non-HLA autoreactivity was not associated with increased rates of ABMRh. CONCLUSIONS: This study shows that patients highly and broadly sensitized against non-HLA targets are associated with an increased risk of ABMR histology after kidney transplantations in the absence of HLA-DSA. Also, some pretransplant non-HLA autoantibodies are individually associated with increased rates of ABMR histology. However, whether these associations are clinically relevant and represent causality, warrants further studies.


Assuntos
Transplante de Rim , Rejeição de Enxerto , Antígenos HLA , Humanos , Isoanticorpos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos
14.
Kyobu Geka ; 75(2): 111-113, 2022 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-35249086

RESUMO

We report a case of delayed hemolytic transfusion reaction (DHTR) after mitral valve replacement (MVR). A 67-year-old woman with a history of blood transfusion( BT) was admitted for MVR. Preoperative laboratory test proved to be negative for irregular antibodies except anti-Dia. She underwent MVR using a mechanical prosthesis and compatible blood products were transfused perioperatively. On post-operative day 13, she developed hemoglobinuria and anemia with elevated serum total bilirubin and lactic dehydrogenase levels. Transesophageal echocardiography showed trivial transvalvular leakage. Laboratory test successfuly identified another irregular antibody, anti-Jkb antibody. The patient had Jkb negative BT and did not need re-operation. Later, she recovered with no signs of hemolysis. Since anti-Jkb antibody gets undetectable within a few months, it is difficult to find out before surgery. As hemolysis following cardiac surgery is more commonly associated with prostheses and extracorporeal circulation than DHTR. Physicians should, however, be aware of this unusual complication especially in patients who underwent BT.


Assuntos
Anemia Hemolítica , Reação Transfusional , Idoso , Anemia Hemolítica/etiologia , Transfusão de Sangue , Feminino , Hemólise , Humanos , Isoanticorpos , Valva Mitral/cirurgia , Reação Transfusional/complicações
15.
Front Immunol ; 13: 818569, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281018

RESUMO

Despite the critical role of cytokines in allograft rejection, the relation of peripheral blood cytokine profiles to clinical kidney transplant rejection has not been fully elucidated. We assessed 28 cytokines through multiplex assay in 293 blood samples from kidney transplant recipients at time of graft dysfunction. Unsupervised hierarchical clustering identified a subset of patients with increased pro-inflammatory cytokine levels. This patient subset was hallmarked by a high prevalence (75%) of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA) and histological rejection (70%) and had worse graft survival compared to the group with low cytokine levels (HLA-DSA in 1.7% and rejection in 33.7%). Thirty percent of patients with high pro-inflammatory cytokine levels and HLA-DSA did not have histological rejection. Exploring the cellular origin of these cytokines, we found a corresponding expression in endothelial cells, monocytes, and natural killer cells in single-cell RNASeq data from kidney transplant biopsies. Finally, we confirmed secretion of these cytokines in HLA-DSA-mediated cross talk between endothelial cells, NK cells, and monocytes. In conclusion, blood pro-inflammatory cytokines are increased in kidney transplant patients with HLA-DSA, even in the absence of histology of rejection. These observations challenge the concept that histology is the gold standard for identification of ongoing allo-immune activation after transplantation.


Assuntos
Transplante de Rim , Soro Antilinfocitário , Citocinas , Células Endoteliais , Rejeição de Enxerto , Humanos , Isoanticorpos
16.
Blood Transfus ; 20(2): 132-142, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35244534

RESUMO

Despite stringent testing protocols, there always remains a chance of a delayed haemolytic transfusion reaction (DHTR) occurring as a result of an undetected or unknown antibody. In this systemic review and meta-analysis, we aimed to investigate improvements to patient outcomes that could be achieved through the implementation of a national antibody registry. A series of searches through PubMed and SCOPUS identified a collection of articles with relevant information, restricted to full text, English language articles available through the RMIT Library service. 25 articles were considered for the review, four of these found to have relevant, extractable data for use in the meta-analysis. Alloantibody evanescence rates were analysed for the potential for reducing DHTRs associated with transfusion services, returning significant results indicating antibody evanescence rates of up to 68.4% in one study, with p-values less than 0.001. Due to the small number of included studies however, the interference values were quite high for these analyses at greater than 90% for each. Additional, beneficial side-effects of such a system were also considered, along with reductions in DHTRs. In conclusion it was determined that a National antibody registry would contribute to improving patient outcomes, however further studies could be performed to determine a stronger correlation, and exact levels of improvement that could be achieved.


Assuntos
Isoanticorpos , Humanos
19.
Hum Immunol ; 83(3): 199-203, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35193786

RESUMO

This article describes my personal perspectives on HLA epitopes. It is not intended to be a general review of HLA epitopes as several versions have been published before. This article is an autobiographical reflection with three sections. The first part named "Past" is intended to show how traditional HLA typing and serological HLA data might be interpreted with epitopes. The second section named "Present" describes my experience with HLA epitopes including antibody verification and the concept of ^eplet load. The third part, "Future", expresses my (thoughts about HLA epitopes and their application in the clinical setting. The list of cited References includes publications selected from the HLAMatchmaker website www.epitopes.net. Most of these references have PDF documents than can be downloaded without charge.


Assuntos
Anticorpos , Antígenos HLA , Epitopos , Rejeição de Enxerto , Teste de Histocompatibilidade , Humanos , Isoanticorpos
20.
Transplant Proc ; 54(2): 335-340, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35101323

RESUMO

BACKGROUND: Preemptive living donor kidney transplantation (P-LDKT) has shown a better prognosis than nonpreemptive living donor KT (NP-LDKT) or deceased donor KT (DDKT). However, association between KT type and de novo donor specific antibody (dnDSA) is uncertain. MATERIALS: We retrospectively analyzed 1114 patients who underwent KT between 1994 and 2020. We investigated the clinical significance of dnDSA based on KT type. RESULTS: Mean follow-up duration was 131.5 ± 89.5 months. Mean age of recipients, mismatched number of human leukocyte antigens and incidence of delayed graft function were significantly higher in DDKT group than P-LDKT and NP-LDKT groups. There were no significant differences of incidence of dnDSA and acute rejection within 1 year among them. Death-censored graft survival rate was significantly lower in all groups with dnDSA than without dnDSA, respectively. In positive dnDSA, NP-LDKT and DDKT groups tended to be lower in the death-censored graft survival compared to P-LDKT and there was a significant interaction between type of KT and dnDSA (P = .010). Independent risk factors were acute rejection within 1 year (hazard ratio [HR], 4.341; 95% CI, 1.758-10.720; P = .001), dnDSA positivity (HR, 3.170; 95% CI, 1.364-7.371; P = .007), and eGFR at 12 months after KT (HR, 3.701; 95% CI 2.049-6.686; P < .001). CONCLUSIONS: There was no significant difference of incidence of dnDSA based on KT type, but allograft survival was poor in all recipients with dnDSA. NP-LDKT and DDKT with dnDSA showed poor prognosis compared to P-LDKT with dnDSA. Therefore, continuous and rigorous surveillance of DSA needs among NP-LDKT and DDKT.


Assuntos
Transplante de Rim , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Isoanticorpos , Transplante de Rim/efeitos adversos , Doadores Vivos , Estudos Retrospectivos
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