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1.
Front Immunol ; 15: 1384823, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840925

RESUMO

Objective: In a cooperative study of the University Hospital Leipzig, University of Leipzig, and the Charité Berlin on kidney transplant patients, we analysed the occurrence of HLA-specific antibodies with respect to the HLA setup of the patients. We aimed at the definition of specific HLA antigens towards which the patients produced these antibodies. Methods: Patients were typed for the relevant HLA determinants using mainly the next-generation technology. Antibody screening was performed by the state-of-the-art multiplex-based technology using microspheres coupled with the respective HLA alleles of HLA class I and II determinants. Results: Patients homozygous for HLA-A*02, HLA-A*03, HLA-A*24, HLA-B*07, HLA-B*18, HLA-B*35, HLA-B*44, HLA-C*03, HLA-C*04, and HLA-C*07 in the class I group and HLA-DRB1*01, HLA-DRB1*03, HLA-DRB1*07, HLA-DRB1*15, HLA-DQA1*01, HLA-DQA1*05, HLA-DQB1*02, HLA-DQB1*03(7), HLA-DQB1*06, HLA-DPA1*01, and HLA-DPB1*04 in the class II group were found to have a significant higher antibody production compared to the heterozygous ones. In general, all HLA determinants are affected. Remarkably, HLA-A*24 homozygous patients can produce antibodies towards all HLA-A determinants, while HLA-B*18 homozygous ones make antibodies towards all HLA-B and selected HLA-A and C antigens, and are associated with an elevation of HLA-DRB1, parts of DQB1 and DPB1 alleles. Homozygosity for the HLA class II HLA-DRB1*01, and HLA-DRB1*15 seems to increase the risk for antibody responses against most of the HLA class I antigens (HLA-A, HLA-B, and HLA-C) in contrast to HLA-DQB1*03(7) where a lower risk towards few HLA-A and HLA-B alleles is found. The widely observed differential antibody response is therefore to be accounted to the patient's HLA type. Conclusion: Homozygous patients are at risk of producing HLA-specific antibodies hampering the outcome of transplantation. Including this information on the allocation procedure might reduce antibody-mediated immune reactivity and prevent graft loss in a patient at risk, increasing the life span of the transplanted organ.


Assuntos
Antígenos HLA , Homozigoto , Isoanticorpos , Transplante de Rim , Humanos , Fatores de Risco , Antígenos HLA/genética , Antígenos HLA/imunologia , Isoanticorpos/imunologia , Teste de Histocompatibilidade , Alelos , Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Masculino , Feminino
2.
J Clin Invest ; 134(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828725

RESUMO

Although antibody-mediated lung damage is a major factor in transfusion-related acute lung injury (ALI), autoimmune lung disease (for example, coatomer subunit α [COPA] syndrome), and primary graft dysfunction following lung transplantation, the mechanism by which antigen-antibody complexes activate complement to induce lung damage remains unclear. In this issue of the JCI, Cleary and colleagues utilized several approaches to demonstrate that IgG forms hexamers with MHC class I alloantibodies. This hexamerization served as a key pathophysiological mechanism in alloimmune lung injury models and was mediated through the classical pathway of complement activation. Additionally, the authors provided avenues for exploring therapeutics for this currently hard-to-treat clinical entity that has several etiologies but a potentially focused mechanism.


Assuntos
Lesão Pulmonar Aguda , Ativação do Complemento , Imunoglobulina G , Humanos , Imunoglobulina G/imunologia , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Ativação do Complemento/imunologia , Animais , Isoanticorpos/imunologia , Multimerização Proteica/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Complexo Antígeno-Anticorpo/imunologia
3.
HLA ; 103(6): e15560, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38839559

RESUMO

De novo anti-HLA donor-specific antibodies (DSAs) were rarely reported in stem cell transplantation patients. We present a case of 39-year-old acute myelogenous leukaemia patient who developed de novo DSAs only 16 days after transplantation with the highest mean fluorescence intensity (MFI) of 7406.23, which were associated with poor graft function (PGF). We used plasma exchange (PE) and intravenous immunoglobulin (IVIg) to reduce DSA level. A series of treatment including mesenchymal stem cells and donor cell transfusion were used to help recover graft function. On day 130, the patient achieved a successful engraftment.


Assuntos
Antígenos HLA , Transplante de Células-Tronco Hematopoéticas , Isoanticorpos , Leucemia Mieloide Aguda , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Antígenos HLA/imunologia , Isoanticorpos/imunologia , Isoanticorpos/sangue , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/imunologia , Masculino , Doadores de Tecidos , Transplante Haploidêntico/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Troca Plasmática/métodos , Feminino , Teste de Histocompatibilidade
4.
J Pregnancy ; 2024: 5539776, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883212

RESUMO

Background: There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant women. Methods: Using the microcolumn gel antiglobulin method, 18,010 Chinese women with a history of pregnancy and pregnant women were screened for irregular RBC antibodies, and for those with positive test results, antibody specificity was determined. The detection rate and specificity of irregular RBC antibodies in women with a history of multiple pregnancies (two or more) and first-time pregnant women were determined. Results: In addition to 25 patients who passively acquired anti-D antibodies via an intravenous anti-D immunoglobulin injection, irregular RBC antibodies were detected in 121 (0.67%) of the 18,010 women. Irregular RBC antibodies were detected in 93 (0.71%) of the 13,027 women with a history of multiple pregnancies, and antibody specificity was distributed mainly in the Rh, MNSs, Lewis, and Kidd blood group systems; irregular RBC antibodies were detected in 28 (0.56%) of the 4983 first-time pregnant women, and the antibody specificity was distributed mainly in the MNSs, Rh, and Lewis blood group systems. The difference in the percentage of patients with irregular RBC antibodies between the two groups was insignificant (χ 2 = 1.248, P > 0.05). Of the 121 women with irregular RBC antibodies, nine had anti-Mur antibodies, and one had anti-Dia antibodies; these antibodies are clinically important but easily missed because the antigenic profile of the reagent RBCs that are commonly used in antibody screens does not include the antigens that are recognized by these antibodies. Conclusion: Irregular RBC antibody detection is clinically important for both pregnant women with a history of multiple pregnancies and first-time pregnant women. Mur and Dia should be included in the antigenic profile of reagent RBCs that are used for performing antibody screens in the Chinese population.


Assuntos
Eritrócitos , Humanos , Feminino , Gravidez , Eritrócitos/imunologia , China , Adulto , Gravidez Múltipla , Isoanticorpos/sangue , Imunoglobulina rho(D)/sangue , Sensibilidade e Especificidade , Especificidade de Anticorpos , Sistema do Grupo Sanguíneo MNSs/imunologia , Povo Asiático , Sistema do Grupo Sanguíneo Kidd/imunologia , População do Leste Asiático
5.
Pediatrics ; 153(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38784990

RESUMO

BACKGROUND AND OBJECTIVES: Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in ∼4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. METHODS: We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. RESULTS: A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. CONCLUSIONS: Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia.


Assuntos
Eritroblastose Fetal , Isoanticorpos , Isoimunização Rh , Humanos , Feminino , Gravidez , Recém-Nascido , Isoanticorpos/imunologia , Isoanticorpos/sangue , Isoimunização Rh/imunologia , Isoimunização Rh/epidemiologia , Eritroblastose Fetal/imunologia , Eritroblastose Fetal/epidemiologia , Eritroblastose Fetal/diagnóstico , Resultado da Gravidez/epidemiologia , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Masculino , Imunoglobulina rho(D)/imunologia , Adulto , Estudos Retrospectivos
6.
Transpl Immunol ; 84: 102049, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729449

RESUMO

INTRODUCTION: Antibody-mediated rejection (AMR) is the most common cause of immune-mediated allograft failure after kidney transplant and impacts allograft survival. Previous sensitization is a major risk factor for development of donor specific antibodies (DSA). AMR can have a wide range of clinical features such as impaired kidney function, proteinuria/hypertension or can be subclinical. HLA molecules have specific regions of antigens binding antibodies called epitopes and eplets are considered essential components responsible for immune recognition. We present a patient with subclinical AMR 1 week post transplantation. CASE REPORT: A 48-year-old, caucasian woman with end-stage kidney disease (ESKD) secondary to autosomal dominant polycystic kidney disease (ADPKD) on peritoneal dialysis was registered in deceased donor waitlist. She was a hypersensitized patient from 3 prior pregnancies with a calculated panel reactive antibody of 93,48%. She was transplanted through kidney paired exchange donation with no evidence of DSA pre transplantation. Surgery and post-op were unremarkable with excellent and immediate graft function. Per protocol DSA levels on the 5th day was DR1 of 3300 MFI, with an increase in MFI by day 13 with 7820 MFI and a new B41 1979MFI. Allograft kidney biopsy findings were diagnostic of AMR and she was treated with immunoglobulin and plasmapheresis. As early onset AMR post transplantation was observed an anamnestic response was hypothesized from a previous exposure to allo-HLA. We decided to type her husband, her son's father, which was presented with DSA. Mismatch eplet analysis revealed a shared 41 T and 67LQ eplets between the donor and husband, responsible for the reactivity and new HLA class I B41 and HLA class II DR1 DSA, respectively. DISCUSSION: Shared eplets between the patient husband and donor was responsible for the alloimmune response and early development of DSAs. This case highlights the importance of early monitoring DSA levels in highly sensitized patients after transplant in order to promptly address and lower inflammatory damage. Mismatch eplet analysis can provide a thorough and precise evaluation of immune compatibility providing a useful technique to immune risk stratification, donor selection and post-transplant immunosuppressive therapy and monitoring.


Assuntos
Rejeição de Enxerto , Teste de Histocompatibilidade , Isoanticorpos , Falência Renal Crônica , Transplante de Rim , Humanos , Feminino , Pessoa de Meia-Idade , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/diagnóstico , Isoanticorpos/imunologia , Isoanticorpos/sangue , Falência Renal Crônica/imunologia , Falência Renal Crônica/cirurgia , Falência Renal Crônica/terapia , Antígenos HLA/imunologia , Rim Policístico Autossômico Dominante/imunologia , Doadores de Tecidos
7.
Transpl Immunol ; 84: 102054, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38750972

RESUMO

BACKGROUND: Immune-mediated rejection is the most common cause of allograft failure in kidney transplant (KT) patients. Exposure to alloantigen, including human leukocyte antigen (HLA), results in the production of donor-specific antibodies (DSA). There are limited data about low levels of mean fluorescence intensity (MFI) DSA, especially post-transplantation. This study evaluated allograft outcomes in KT patients with low MFI DSA. METHODS: From January 2007 to December 2021, KT patients who were tested for post-transplant DSA at Ramathibodi Hospital, Bangkok, Thailand, with the DSA MFI ≤ 1000 were evaluated. These KT patients were categorized into two groups: very low DSA (VLL; MFI = 1-500) and low DSA (LL; MFI = 501-1000). All KT patients were evaluated for the primary outcomes, such as the incidence of acute rejection, serum creatinine levels at one and five years after transplantation as well as allograft and patient survivals. RESULTS: Among 36 KT patients 25 were included as those with VLL and 11 as those with LL. The LL group had significantly higher T-cell mediated allograft rejection (TCMR) than the VLL group (45% vs. 12%, P = 0.04). In addition, 10 patients, 5 in the VLL group and 5 in the LL group developed antibody-mediated allograft rejection (ABMR). Both TCMR and ABMR were confirmed by biopsy results. There was a trend toward higher MFI in KT patients with ABMR than without ABMR (P = 0.22). At 5 post-transplant years, serum creatinine, allograft and patient survivals were comparable between these two groups. Furthermore, the univariate and multivariate analyzes revealed that the LL group was a high risk for rejection. CONCLUSION: Low MFI DSA values after transplantation may be associated with a higher incidence of rejection, but this finding did not show differences in allograft and patient survival in this study's analysis.


Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Antígenos HLA , Isoanticorpos , Transplante de Rim , Doadores de Tecidos , Humanos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/diagnóstico , Masculino , Feminino , Isoanticorpos/sangue , Pessoa de Meia-Idade , Adulto , Antígenos HLA/imunologia , Sobrevivência de Enxerto/imunologia , Aloenxertos/imunologia , Transplante Homólogo , Estudos Retrospectivos
8.
Transfusion ; 64(6): 1167-1170, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38693097

RESUMO

BACKGROUND: Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) results from maternal platelet alloimmunization against paternal antigens inherited by the fetus, most often due to the Human Platelet Antigen (HPA)-1 system in Caucasians. We investigated in 2023, a 30-year-old Caucasian woman Gravida 2 Para 1 who gave birth at 35 weeks of gestation to a male (body weight 2210 g) without signs of bleeding. A severe thrombocytopenia (platelet count at 3 G/L) was discovered incidentally a few hours after delivery in the context of the management of a respiratory distress. The newborn recovered after one platelet concentrate transfusion and normalized his platelet count at Day 5. STUDY DESIGN AND METHODS: FNAIT investigation was performed according to guideline recommendations. Platelet genotyping was carried out by multiplex PCR. Maternal serological investigation included Monoclonal Antibody-specific Immobilization of Platelet Antigens method (MAIPA) and Luminex technology. RESULTS: Parental and newborn genotyping pointed out an HPA-4 incompatibility between the mother and the newborn and the father. Serological investigation revealed an anti-HPA-4b alloantibody confirming the diagnosis of neonatal alloimmune thrombocytopenia. CONCLUSION: We described the third case of anti-HPA-4b alloantibody discovered in a Caucasian mother. This case strengthens the need for reference laboratory to genotype a panel of HPA alleles reflecting local genetic population diversity and for crossmatch of maternal serum with fresh paternal platelets in clinical suspected cases of neonatal alloimmune thrombocytopenia.


Assuntos
Antígenos de Plaquetas Humanas , Isoanticorpos , Trombocitopenia Neonatal Aloimune , Humanos , Isoanticorpos/sangue , Isoanticorpos/imunologia , Trombocitopenia Neonatal Aloimune/imunologia , Trombocitopenia Neonatal Aloimune/sangue , Feminino , Antígenos de Plaquetas Humanas/imunologia , Antígenos de Plaquetas Humanas/genética , Recém-Nascido , Adulto , Gravidez , Masculino , Transfusão de Plaquetas , População Branca
9.
Xenotransplantation ; 31(3): e12862, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38761019

RESUMO

Prolonged survival in preclinical renal xenotransplantation demonstrates that early antibody mediated rejection (AMR) can be overcome. It is now critical to evaluate and understand the pathobiology of late graft failure and devise new means to improve post xenograft outcomes. In renal allotransplantation the most common cause of late renal graft failure is transplant glomerulopathy-largely due to anti-donor MHC antibodies, particularly anti-HLA DQ antibodies. We evaluated the pig renal xenograft pathology of four long-surviving (>300 days) rhesus monkeys. We also evaluated the terminal serum for the presence of anti-SLA class I and specifically anti-SLA DQ antibodies. All four recipients had transplant glomerulopathy and expressed anti-SLA DQ antibodies. In one recipient tested for anti-SLA I antibodies, the recipient had antibodies specifically reacting with two of three SLA I alleles tested. These results suggest that similar to allotransplantation, anti-MHC antibodies, particularly anti-SLA DQ, may be a barrier to improved long-term xenograft outcomes.


Assuntos
Rejeição de Enxerto , Xenoenxertos , Antígenos de Histocompatibilidade Classe I , Transplante de Rim , Macaca mulatta , Transplante Heterólogo , Animais , Transplante Heterólogo/métodos , Rejeição de Enxerto/imunologia , Transplante de Rim/métodos , Antígenos de Histocompatibilidade Classe I/imunologia , Suínos , Xenoenxertos/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Sobrevivência de Enxerto/imunologia , Isoanticorpos/imunologia , Humanos
10.
Clin Immunol ; 264: 110240, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38734036

RESUMO

Kidney transplant (KT) candidates with donor-specific antibodies (DSA) exhibit exceedingly high antibody-mediated rejection (ABMR) and allograft loss rates. Currently, treatment of ABMR remains an unmet clinical need. We report the use of the anti-C5 eculizumab and the type-2 anti-CD20 obinutuzumab in two patients with early ABMR. Eculizumab (900 mg IV) led to complete inhibition of the terminal complement cascade (unremarkable AP50 and CH50 activity) and prompt stoppage of complement-dependent antibody-mediated allograft injury (clearance of intra-graft C4d and C5b-9 deposition). Despite complement inhibition, obinutuzumab (1000 mg IV) determined full and long-lasting peripheral B-cell depletion, with significant reduction in all DSA. Graft function improved, remaining stable up to three years of follow-up. No signs of active ABMR and rebound DSA were detected. Obinutuzumab B-cell depletion and inhibition of DSA production were not affected by complement blockage. Further studies are needed to confirm the potential benefit of obinutuzumab in association with complement inhibitors.


Assuntos
Anticorpos Monoclonais Humanizados , Rejeição de Enxerto , Transplante de Rim , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Masculino , Pessoa de Meia-Idade , Complemento C5/antagonistas & inibidores , Complemento C5/imunologia , Feminino , Antígenos CD20/imunologia , Adulto , Linfócitos B/imunologia , Linfócitos B/efeitos dos fármacos , Inativadores do Complemento/uso terapêutico , Isoanticorpos/imunologia
11.
Transplant Proc ; 56(4): 885-891, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38729828

RESUMO

Anti-human leukocyte antigen (anti-HLA) sensitization in lung transplant recipients (LTRs) can significantly impact graft survival and patient outcomes. The global pandemic, induced by the SARS-CoV-2 virus, brought about numerous challenges in the medical sphere, including potential alterations in HLA immunization patterns among LTRs. A retrospective analysis of LTRs group transplanted from July 2018 to 1 March 2020 (pre-pandemic) was compared with patients transplanted from 1 March 2020 to December 2022 (during the pandemic). Totally 92 patients were controlled. Patients were also divided into 2 groups: vaccinated and non-vaccinated. The results of cytotoxic crossmatch, results of anti-HLA antibody testing, presence of DSA before and after transplantation, and early and late graft function were compared between groups. In the pandemic and vaccinated groups, an increase was observed in the number of positive crossmatch tests performed with a pool of B lymphocytes. However, the presence of dithiothreitol abolished the positive reaction in 90% of cases. We also observed an increased percentage of patients immunized based on the results of solid phase tests both in the pandemic group and in the group of patients who received vaccination against the SARS-CoV-2 virus. It might be that the pandemic/vaccination has influenced the prevalence of anti-HLA immunization in LTRs. Further studies are essential to establish causative factors and develop targeted interventions for this population of patients.


Assuntos
COVID-19 , Antígenos HLA , Transplante de Pulmão , Humanos , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/epidemiologia , Antígenos HLA/imunologia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , SARS-CoV-2/imunologia , Teste de Histocompatibilidade , Sobrevivência de Enxerto , Isoanticorpos/sangue , Pandemias , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Imunização
12.
Immunohematology ; 40(1): 15-27, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38739027

RESUMO

In pregnancy, D- pregnant women may be at risk of becoming immunized against D when carrying a D+ fetus, which may eventually lead to hemolytic disease of the fetus and newborn. Administrating antenatal and postnatal anti-D immunoglobulin prophylaxis decreases the risk of immunization substantially. Noninvasive fetal RHD genotyping, based on testing cell-free DNA extracted from maternal plasma, offers a reliable tool to predict the fetal RhD phenotype during pregnancy. Used as a screening program, antenatal RHD screening can guide the administration of antenatal prophylaxis in non-immunized D- pregnant women so that unnecessary prophylaxis is avoided in those women who carry a D- fetus. In Europe, antenatal RHD screening programs have been running since 2009, demonstrating high test accuracies and program feasibility. In this review, an overview is provided of current state-of-the-art antenatal RHD screening, which includes discussions on the rationale for its implementation, methodology, detection strategies, and test performance. The performance of antenatal RHD screening in a routine setting is characterized by high accuracy, with a high diagnostic sensitivity of ≥99.9 percent. The result of using antenatal RHD screening is that 97-99 percent of the women who carry a D- fetus avoid unnecessary prophylaxis. As such, this activity contributes to avoiding unnecessary treatment and saves valuable anti-D immunoglobulin, which has a shortage worldwide. The main challenges for a reliable noninvasive fetal RHD genotyping assay are low cell-free DNA levels, the genetics of the Rh blood group system, and choosing an appropriate detection strategy for an admixed population. In many parts of the world, however, the main challenge is to improve the basic care for D- pregnant women.


Assuntos
Sistema do Grupo Sanguíneo Rh-Hr , Imunoglobulina rho(D) , Humanos , Gravidez , Feminino , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Sistema do Grupo Sanguíneo Rh-Hr/genética , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Imunoglobulina rho(D)/uso terapêutico , Imunoglobulina rho(D)/sangue , Diagnóstico Pré-Natal/métodos , Isoanticorpos/sangue , Isoanticorpos/imunologia , Eritroblastose Fetal/prevenção & controle , Eritroblastose Fetal/diagnóstico , Eritroblastose Fetal/sangue , Eritroblastose Fetal/imunologia
13.
J Clin Apher ; 39(3): e22120, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38733134

RESUMO

Anti-PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti-PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti-PP1PK alloimmunization in a 23-year-old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti-PP1Pk titers. Twice-weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery-peak systolic velocities (MCA-PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen-negative, ABO-compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA-PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice-weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti-PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti-PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan.


Assuntos
Imunoglobulinas Intravenosas , Troca Plasmática , Humanos , Troca Plasmática/métodos , Feminino , Gravidez , Imunoglobulinas Intravenosas/uso terapêutico , Adulto Jovem , Eritroblastose Fetal/terapia , Eritroblastose Fetal/prevenção & controle , Recém-Nascido , Isoanticorpos/sangue , Isoanticorpos/imunologia , Adulto
14.
Transpl Int ; 37: 12774, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779355

RESUMO

Lung transplantation (LuTx) is an established treatment for patients with end-stage lung diseases, however, outcomes are limited by acute and chronic rejection. One aspect that has received increasing attention is the role of the host's humoral alloresponse, particularly the formation of de novo donor-specific antibodies (dnDSAs). The aim of this study was to investigate the clinical significance of transient and persistent dnDSAs and to understand their impact on outcomes after LuTx. A retrospective analysis was conducted using DSA screening data from LuTx recipients obtained at the Medical University of Vienna between February 2016 and March 2021. Of the 405 LuTx recipients analyzed, 205 patients developed dnDSA during the follow-up period. Among these, 167 (81%) had transient dnDSA and 38 (19%) persistent dnDSA. Persistent but not transient dnDSAs were associated with chronic lung allograft dysfunction (CLAD) and antibody-mediated rejection (AMR) (p < 0.001 and p = 0.006, respectively). CLAD-free survival rates for persistent dnDSAs at 1-, 3-, and 5-year post-transplantation were significantly lower than for transient dnDSAs (89%, 59%, 56% vs. 91%, 79%, 77%; p = 0.004). Temporal dynamics of dnDSAs after LuTx have a substantial effect on patient outcomes. This study underlines that the persistence of dnDSAs poses a significant risk to graft and patient survival.


Assuntos
Rejeição de Enxerto , Isoanticorpos , Transplante de Pulmão , Doadores de Tecidos , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Rejeição de Enxerto/imunologia , Adulto , Isoanticorpos/imunologia , Isoanticorpos/sangue , Sobrevivência de Enxerto/imunologia , Idoso
15.
Clin Transplant ; 38(5): e15338, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38762787

RESUMO

BACKGROUND: Kidney transplantation is the optimal treatment for end-stage renal disease. However, highly sensitized patients (HSPs) have reduced access to transplantation, leading to increased morbidity and mortality on the waiting list. The Canadian Willingness to Cross (WTC) program proposes allowing transplantation across preformed donor specific antibodies (DSA) determined to be at a low risk of rejection under the adaptive design framework. This study collected patients' perspectives on the development of this program. METHODS: Forty-one individual interviews were conducted with kidney transplant candidates from three Canadian transplant centers in 2022. The interviews were digitally recorded and transcribed for subsequent analyses. RESULTS: Despite limited familiarity with the adaptive design, participants demonstrated trust in the researchers. They perceived the WTC program as a pathway for HSPs to access transplantation while mitigating transplant-related risks. HSPs saw the WTC program as a source of hope and an opportunity to leave dialysis, despite acknowledging inherent uncertainties. Some non-HSPs expressed concerns about fairness, anticipating increased waiting times and potential compromise in kidney graft longevity due to higher rejection risks. Participants recommended essential strategies for implementing the WTC program, including organizing informational meetings and highlighting the necessity for psychosocial support. CONCLUSION: The WTC program emerges as a promising strategy to enhance HSPs' access to kidney transplantation. While HSPs perceived this program as a source of hope, non-HSPs voiced concerns about distributive justice issues. These results will help develop a WTC program that is ethically sound for transplant candidates.


Assuntos
Rejeição de Enxerto , Acessibilidade aos Serviços de Saúde , Falência Renal Crônica , Transplante de Rim , Listas de Espera , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Canadá , Falência Renal Crônica/cirurgia , Falência Renal Crônica/psicologia , Adulto , Rejeição de Enxerto/etiologia , Prognóstico , Seguimentos , Sobrevivência de Enxerto , Doadores de Tecidos/provisão & distribuição , Doadores de Tecidos/psicologia , Obtenção de Tecidos e Órgãos , Idoso , Isoanticorpos/imunologia
16.
Clin Transplant ; 38(5): e15330, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38716787

RESUMO

INTRODUCTION: Since the 2018 change in the US adult heart allocation policy, more patients are bridged-to-transplant on temporary mechanical circulatory support (tMCS). Previous studies indicate that durable left ventricular assist devices (LVAD) may lead to allosensitization. The goal of this study was to assess whether tMCS implantation is associated with changes in sensitization. METHODS: We included patients evaluated for heart transplants between 2015 and 2022 who had alloantibody measured before and after MCS implantation. Allosensitization was defined as development of new alloantibodies after tMCS implant. RESULTS: A total of 41 patients received tMCS before transplant. Nine (22.0%) patients developed alloantibodies following tMCS implantation: 3 (12.0%) in the intra-aortic balloon pump group (n = 25), 2 (28.6%) in the microaxial percutaneous LVAD group (n = 7), and 4 (44.4%) in the veno-arterial extra-corporeal membrane oxygenation group (n = 9)-p = .039. Sensitized patients were younger (44.7 ± 11.6 years vs. 54.3 ± 12.5 years, p = .044), were more likely to be sensitized at baseline - 3 of 9 (33.3%) compared to 2 out of 32 (6.3%) (p = .028) and received more transfusions with red blood cells (6 (66.6%) vs. 8 (25%), p = .02) and platelets (6 (66.6%) vs. 5 (15.6%), p = .002). There was no significant difference in tMCS median duration of support (4 [3,15] days vs. 8.5 [5,14.5] days, p = .57). Importantly, out of the 11 patients who received a durable LVAD after tMCS, 5 (45.5%) became sensitized, compared to 4 out of 30 patients (13.3%) who only had tMCS-p = .028. CONCLUSIONS: Our findings suggest that patients bridged-to-transplant with tMCS, without significant blood product transfusions and a subsequent durable LVAD implant, have a low risk of allosensitization. Further studies are needed to confirm our findings and determine whether risk of sensitization varies by type of tMCS and duration of support.


Assuntos
Transplante de Coração , Coração Auxiliar , Isoanticorpos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Isoanticorpos/imunologia , Isoanticorpos/sangue , Seguimentos , Adulto , Fatores de Risco , Prognóstico , Estudos Retrospectivos , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/terapia , Rejeição de Enxerto/etiologia
17.
Transpl Int ; 37: 12591, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694489

RESUMO

Tacrolimus is pivotal in pancreas transplants but poses challenges in maintaining optimal levels due to recipient differences. This study aimed to explore the utility of time spent below the therapeutic range and intrapatient variability in predicting rejection and de novo donor-specific antibody (dnDSA) development in pancreas graft recipients. This retrospective unicentric study included adult pancreas transplant recipients between January 2006 and July 2020. Recorded variables included demographics, immunosuppression details, HLA matching, biopsy results, dnDSA development, and clinical parameters. Statistical analysis included ROC curves, sensitivity, specificity, and predictive values. A total of 131 patients were included. Those with biopsy-proven acute rejection (BPAR, 12.2%) had more time (39.9% ± 24% vs. 25.72% ± 21.57%, p = 0.016) and tests (41.95% ± 13.57% vs. 29.96% ± 17.33%, p = 0.009) below therapeutic range. Specific cutoffs of 31.5% for time and 34% for tests below the therapeutic range showed a high negative predictive value for BPAR (93.98% and 93.1%, respectively). Similarly, patients with more than 34% of tests below the therapeutic range were associated with dnDSA appearance (38.9% vs. 9.4%, p = 0.012; OR 6.135, 1.346-27.78). In pancreas transplantation, maintaining optimal tacrolimus levels is crucial. Suboptimal test percentages below the therapeutic range prove valuable in identifying acute graft rejection risk.


Assuntos
Rejeição de Enxerto , Imunossupressores , Transplante de Pâncreas , Tacrolimo , Humanos , Rejeição de Enxerto/imunologia , Tacrolimo/uso terapêutico , Masculino , Estudos Retrospectivos , Feminino , Adulto , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Isoanticorpos/sangue , Isoanticorpos/imunologia , Doadores de Tecidos , Fatores de Tempo , Biópsia , Sobrevivência de Enxerto
18.
Pediatr Transplant ; 28(5): e14774, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38808699

RESUMO

BACKGROUND: Antibody-mediated rejection is one of the most significant risk factors for allograft dysfunction and failure in children and adolescents with kidney transplants, yet optimal treatment remains unidentified. To date, there are mixed findings regarding the use of Bortezomib, a plasma cell apoptosis inducer, as an adjunct therapy in the treatment of antibody-mediated rejection. METHODS: In a retrospective single center study, we reviewed the efficacy and tolerability of bortezomib as adjunct therapy for treatment-refractory antibody-mediated rejection. RESULTS: Six patients with a median age of 14.6 years (range 6.9-20.1 years) received bortezomib at a mean of 71 months (range 15-83 months) post-kidney transplant. Four patients experienced decline in estimated glomerular filtration rate (eGFR) from 4% to 42%. One patient started bortezomib while on hemodialysis and did not recover graft function, and another patient progressed to hemodialysis 6 months after receiving bortezomib. Although DSA did not completely resolve, there was a statistically significant decline in DSA MFI pre and 12-months post-BZ (p = .012, paired t-test) for the subjects who were not on dialysis at the time of bortezomib. Chronic Allograft Damage Index (CADI) score of ≥3 was seen in all six subjects at their biopsy prior to therapy. No adverse effects were reported. CONCLUSIONS: Bortezomib was well tolerated and resulted in improvements in MFI of DSA among four pediatric subjects without allograft failure, although no effects were observed on eGFR trajectory. Further studies are needed to clarify whether earlier intervention with bortezomib could prevent renal failure progression.


Assuntos
Bortezomib , Taxa de Filtração Glomerular , Rejeição de Enxerto , Transplante de Rim , Humanos , Bortezomib/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Estudos Retrospectivos , Masculino , Adolescente , Feminino , Criança , Adulto Jovem , Resultado do Tratamento , Imunossupressores/uso terapêutico , Isoanticorpos/imunologia
19.
Pediatr Transplant ; 28(5): e14773, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38808702

RESUMO

BACKGROUND: Optimizing graft survival and diminishing human leukocyte antigen (HLA) sensitization are essential for pediatric kidney transplant recipients. More precise HLA matching predicting epitope mismatches could reduce alloreactivity. We investigated the association of predicted HLA B- and T-cell molecular mismatches with the formation of de novo donor-specific antibodies, HLA antibodies, rejection, and graft survival. METHODS: Forty-nine pediatric kidney transplant recipients transplanted from 2009 to 2020 were retrospectively studied. Donors and recipients were high-resolution HLA typed, and recipients were screened for HLA antibodies posttransplant. HLA-EMMA (HLA Epitope MisMatch Algorithm) and PIRCHE-II (Predicted Indirectly ReCognizable HLA Epitopes) predicted the molecular mismatches. The association of molecular mismatches and the end-points was explored with logistic regression. RESULTS: Five recipients (11%) developed de novo donor-specific antibodies. All five had de novo donor-specific antibodies against HLA class II, with four having HLA-DQ antibodies. We found no associations between PIRCHE-II or HLA-EMMA with de novo donor-specific antibodies, HLA sensitization, graft loss, or rejection. However, we did see a tendency towards an increased odds ratio in PIRCHE-II predicting de novo donor-specific antibodies formation, with an odds ratio of 1.12 (95% CI: 0.99; 1.28) on HLA class II. CONCLUSION: While the study revealed no significant associations between the number of molecular mismatches and outcomes, a notable trend was observed - indicating a reduced risk of dnDSA formation with improved molecular match. It is important to acknowledge, however, that the modest population size and limited observed outcomes preclude us from making definitive conclusions.


Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Antígenos HLA , Teste de Histocompatibilidade , Transplante de Rim , Linfócitos T , Humanos , Rejeição de Enxerto/imunologia , Criança , Sobrevivência de Enxerto/imunologia , Feminino , Masculino , Estudos Retrospectivos , Adolescente , Pré-Escolar , Antígenos HLA/imunologia , Linfócitos T/imunologia , Isoanticorpos/imunologia , Isoanticorpos/sangue , Lactente , Antígenos HLA-B/imunologia , Linfócitos B/imunologia
20.
Hum Immunol ; 85(3): 110806, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38664156

RESUMO

Donor exchange programs were designed to allocate organs for highly sensitized (HS) patients. The allocation algorithm differs slightly among countries and includes different strategies to improve access to transplants in HS patients. However, many HS patients with a calculated panel reactive of antibodies (cPRA) of 100 % remain on the waiting list for a long time. Some allocation algorithms assume immunological risk, including Imlifidase treatment, to increase the chance of transplantation in very HS patients. Here, we describe our unicenter experience of low-risk delisting strategy in 15 HS patients included in the Spanish donor exchange program without donor offers. After delisting, 7 out of 15 HS patients reduced the cPRA below 99.95 % and impacted the reduction of time on the waiting list (p = 0.01), where 5 out of 7 achieved transplantation. Within those HS that remained above 99.95 %, 1 out of 8 was transplanted. All the HS were transplanted with delisted DSA, and only one with DSA level rebounded early after transplantation. All HS transplanted after delisting maintain graft function. The transplant immunology laboratories are challenged to search intermediate risk assessment methods for delisting high HS patients.


Assuntos
Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Listas de Espera , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Transplante de Rim , Isoanticorpos/imunologia , Isoanticorpos/sangue , Idoso , Sobrevivência de Enxerto/imunologia , Espanha , Antígenos HLA/imunologia , Teste de Histocompatibilidade/métodos , Algoritmos
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