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1.
Transfusion ; 61 Suppl 1: S144-S149, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269429

RESUMO

INTRODUCTION: Widely varying rates of alloimmunization associated with transfusing uncrossmatched RBC products to trauma patients as part of hemostatic resuscitation have been reported. We characterized the rates of RBC alloimmunization in our severely injured Rh(D) negative trauma population who received uncrossmatched Rh(D) positive RBC products. METHODS: In a 10-year retrospective analysis to assess Rh(D) alloimmunization risks, Rh(D) negative adult trauma patients initially requiring uncrossmatched group O Rh(D) positive RBC products with either RBC units or low titer group O whole blood as part of massive transfusion protocol (MTP) activation were identified. Only those Rh(D) negative patients whose initial antibody screenings were negative were included. Duration of serologic follow-up from date of MTP activation to either date of anti-D detection or most recent negative antibody screening was calculated. RESULTS: There were 129 eligible Rh(D) negative trauma patients identified. Median injury severity score was 25. Anti-D was detected in 10 (7.8%) patients after a median of 161.5 days; the median duration of serologic follow-up in those who did not have anti-D detected was 220 days. Patients who had anti-D detected were less severely injured and received fewer Rh(D) positive RBC products versus those who did not. DISCUSSION: In our severely injured adult trauma patients with MTP activation requiring uncrossmatched group O Rh(D) positive RBC products, the rate of anti-D detection was low. Additional studies are necessary to determine generalizability of these findings and fully characterize alloimmunization risks in trauma patients with varying extents of injury.


Assuntos
Transfusão de Eritrócitos/efeitos adversos , Isoanticorpos/imunologia , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Imunoglobulina rho(D)/imunologia , Ferimentos e Lesões/imunologia , Adulto , Tipagem e Reações Cruzadas Sanguíneas , Feminino , Humanos , Escala de Gravidade do Ferimento , Isoanticorpos/sangue , Masculino , Estudos Retrospectivos , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Imunoglobulina rho(D)/sangue , Ferimentos e Lesões/sangue , Ferimentos e Lesões/terapia
2.
Transfusion ; 61 Suppl 1: S150-S158, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269438

RESUMO

INTRODUCTION: Early transfusion reduces mortality in bleeding patients. In this setting, RhD-positive blood products might be transfused. This study determined the association between the RhD-alloimmunization rate and the number of RhD-positive products transfused. METHODS: RhD-negative patients between 13 and 50 years who were transfused with ≥1 RhD-positive red blood cell (RBC) or whole blood units between January 1, 2000 and December 31, 2019 in a healthcare network were identified. Study patients had to have had at least one antibody detection test performed ≥14 days after the index RhD-positive transfusion and not receive RhIg. Patients were stratified into groups that received 1, 2, 3-5, 6-10, 11-20, and >20 RhD-positive transfusions and the RhD-alloimmunization rate was determined for each group. RESULTS: There were 335 patients included; 52/335 (15.5%) were females. Overall, there were 117/335 (34.9%, CI: 29.8%-40.3%) recipients who became RhD-alloimmunized. There was no significant dosage effect in the RhD-alloimmunization rates as the exposure to RhD-positive units increased from one RhD-positive unit to more than 20 RhD-positive units (p = .270 for non-parametric trend test). In an exploratory analysis, patients who received 100% of their RhD-positive transfusions within 72 h of the index transfusion had a significantly higher rate of RhD-alloimmunization compared to those who were transfused over a longer period of time (42.3% vs. 21.4%, respectively; p = .001). CONCLUSION: These results suggest that there may not be an increased RhD-alloimmunization risk with transfusing multiple RhD-positive units after one RhD-positive unit has been transfused. These findings need confirmation in larger studies.


Assuntos
Transfusão de Eritrócitos/efeitos adversos , Eritrócitos/imunologia , Isoanticorpos/imunologia , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Adulto , Feminino , Humanos , Isoanticorpos/sangue , Masculino , Pessoa de Meia-Idade , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Adulto Jovem
3.
Transfus Apher Sci ; 60(5): 103188, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34144875

RESUMO

OBJECTIVES AND BACKGROUND: In December 2019, the first case of COVID-19 was reported in Wuhan, China. Its causative virus, is a novel strain of RNA viruses with high mortality rate. There is no definitive treatment, but among available approaches the use of recovered patients' plasma containing specific antibodies can enhance the immune response against coronavirus. However, the dearth of eligible donors and also ABO incompatibility in plasma transfusion, have limited this therapeutic method. Therefore, it is highly desirable to introduce a simple procedure that allows efficient reduction or even removal of natural ABO antibodies. Accordingly, we aimed to evaluate a RBC-mediated adsorption technique that reduces the titer of the mentioned antibodies in plasma. METHODS/MATERIALS: This experimental study was conducted in Kerman University of Medical Sciences, Kerman, Iran. The pre- and post-incubation antibody titers of 168 plasma samples were determined. For incubation, each plasma sample was exposed (60 min) to different percentages of RBCs at room temperature or 4 °C. RESULTS: The results evidenced that both the concentration of RBCs and temperature had significant decreasing effects on antibody titer (P < 0.001) and all concentrations significantly reduced titer. Compared to RT, 4 °C further reduced the antibody titer. Overall, the best incubation condition for reducing antibody titer in all blood groups was 4 °C and 2% RBCs concentration. CONCLUSION: The presented adsorption procedure is able to produce universal plasma (we call it Ubiquitous Convalescent Plasma) with a non-immunogenic level of ABO mismatch antibodies which can be used for COVID-19 patients with any type of blood group with desirable simplicity, feasibility, and efficacy.


Assuntos
COVID-19/terapia , Técnicas de Imunoadsorção , Isoanticorpos/sangue , Plasma , SARS-CoV-2 , Sistema ABO de Grupos Sanguíneos/imunologia , Adsorção , Antígenos de Grupos Sanguíneos , COVID-19/sangue , Temperatura Baixa , Convalescença , Contagem de Eritrócitos , Eritrócitos/imunologia , Humanos , Imunização Passiva/métodos , Isoanticorpos/imunologia
6.
Medicine (Baltimore) ; 100(21): e25958, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032705

RESUMO

RATIONALE: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been demonstrated to increase the risk of antibody-mediated rejection. We report a case of AT1R-Ab mediated rejection which caused early critical cortical infarction. PATIENT CONCERNS: A 52-year-old man with end-stage kidney disease underwent preemptive kidney transplantation (KT) from his wife. He had no immunologic risk except ABO incompatibility. Proper desensitization treatment were applied prior to KT. On postoperative day 1, he showed stable clinical course with adequate urine output, but there was no decrease in serum creatinine level and imaging studies showed hypoperfusion in the transplanted kidney. DIAGNOSES: Allograft biopsy revealed total cortical infarction with severe necrotizing vasculitis, but the medullary area was preserved. Serum AT1R-Ab concentration was elevated from 10.9 U/mL before KT to 19.1 U/mL on 7 days after KT. INTERVENTIONS: He was treated with plasmapheresis, intravenous immunoglobulin, rituximab, high-dose methylprednisolone, and bortezomib. OUTCOMES: The treatment showed a partial response, and he was discharged with 7.3 mg/dL creatinine level. At 4 months, his creatinine plateaued at 5.5 mg/dL and AT1R-Ab decreased to 3.6 U/mL. LESSONS: This case highlights the risk of early active antibody-mediated rejection by preformed AT1R-Ab, suggesting its ability to exhibit atypical histopathologic findings, such as total cortical infarction.


Assuntos
Rejeição de Enxerto/imunologia , Infarto/imunologia , Isoanticorpos/sangue , Necrose do Córtex Renal/imunologia , Transplante de Rim/efeitos adversos , Receptor Tipo 1 de Angiotensina/imunologia , Aloenxertos/irrigação sanguínea , Aloenxertos/imunologia , Aloenxertos/patologia , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Teste de Histocompatibilidade , Humanos , Fatores Imunológicos/administração & dosagem , Infarto/sangue , Infarto/diagnóstico , Infarto/terapia , Isoanticorpos/imunologia , Córtex Renal/irrigação sanguínea , Córtex Renal/imunologia , Córtex Renal/patologia , Necrose do Córtex Renal/sangue , Necrose do Córtex Renal/diagnóstico , Necrose do Córtex Renal/terapia , Falência Renal Crônica/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Plasmaferese , Cônjuges , Fatores de Tempo
7.
Transfusion ; 61(7): 2054-2063, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33960433

RESUMO

BACKGROUND: Daratumumab, a human anti-CD38 monoclonal antibody used to treat multiple myeloma, interferes with pretransfusion testing and can mask alloantibodies. Incidence of alloimmunization in patients on daratumumab has not been well characterized, and optimal transfusion guidelines regarding prophylactic antigen matching, accounting for both patient safety and efficiency, have not been well established for these patients. METHODS: Records of patients who received daratumumab between January 1, 2014 and July 2, 2019 were reviewed. Daratumumab interference with pretransfusion testing was managed by testing with reagent red blood cells (RBCs) treated with 0.2 M dithiothreitol. When daratumumab was present during antibody testing, patients were transfused with RBC units prophylactically matched for D, C, c, E, e, and K antigens per hospital policy. RESULTS: Out of 90 patients identified, 52 received a total of 638 RBC transfusions (average of 12.3 units per patient, SD 17.2, range 1-105, median 5 among those transfused). Alloantibodies existing before daratumumab initiation were identified in seven patients. No new alloantibodies were detected in any patients after starting daratumumab treatment. CONCLUSIONS: The incidence of alloimmunization in patients receiving daratumumab is low. Whether this is due to the effect of daratumumab, underlying pathophysiology, or other factors, is unknown. Because these patients require a large number of RBC transfusions overall and have little observed alloimmunization, phenotype matching (beyond RhD) may be unnecessary. Since the use of dithiothreitol cannot rule out the presence of anti-K, we recommend transfusion of ABO-compatible units, prophylactically matched for the D and K antigens only.


Assuntos
Anticorpos Monoclonais/imunologia , Antineoplásicos Imunológicos/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Artefatos , Incompatibilidade de Grupos Sanguíneos/sangue , Tipagem e Reações Cruzadas Sanguíneas , Transfusão de Sangue , Eritrócitos/imunologia , Isoanticorpos/sangue , Mieloma Múltiplo/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/diagnóstico , Incompatibilidade de Grupos Sanguíneos/epidemiologia , Tipagem e Reações Cruzadas Sanguíneas/métodos , Terapia Combinada , Ditiotreitol/farmacologia , Eritrócitos/efeitos dos fármacos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Incidência , Isoanticorpos/biossíntese , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Transplante Autólogo
8.
Transfusion ; 61(7): 2035-2040, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33983627

RESUMO

BACKGROUND: Delayed hemolytic transfusion reactions (DHTRs) are reported to be rare occurrences but may be more frequently observed in the trauma setting where patients are heavily transfused, followed over long inpatient admissions, and have frequent subsequent blood counts as they undergo multiple surgical interventions. STUDY DESIGN AND METHODS: We examined the rates of DHTRs on a per transfusion and per patient basis in an academic county hospital with a level 1 trauma center serving a four-state region and over a 3-year period. DHTRs were entered sequentially into a registry as they were observed, and a retrospective review of all new alloantibodies detected was performed to identify any additional DHTRs. The number of units of red blood cells (RBCs), the number of unique patients, types of alloantibodies, and number of transfusions were extracted from blood bank records. RESULTS: Twenty-nine DHTRs were observed from January 1, 2017, through December 31, 2019, from newly observed alloantibodies after a median of 12 red blood cells (RBCs) transfusions per patient. These reactions occurred in response to 24,633 unique transfusions in 6905 unique patients, so the observed rates were about 1:849 RBC transfusions and 1:238 transfused patients. Evidence of delayed hemolysis was seen in five additional patients who were transfused during emergency resuscitation and later found to have had known RBC antibodies. DISCUSSION: We report a higher rate of DHTRs than previously described to demonstrate that DHTRs are not rare in trauma centers.


Assuntos
Anemia Hemolítica/epidemiologia , Reação Transfusional/epidemiologia , Centros de Traumatologia/estatística & dados numéricos , Centros Médicos Acadêmicos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica/etiologia , Criança , Pré-Escolar , Emergências , Eritrócitos/imunologia , Feminino , Humanos , Incidência , Isoanticorpos/sangue , Masculino , Pessoa de Meia-Idade , Noroeste dos Estados Unidos/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo
9.
Transplantation ; 105(6): 1317-1325, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34019363

RESUMO

BACKGROUND: In March 2016, Australia's deceased donor kidney allocation program introduced calculated panel reactive antibody (cPRA) based on antibody exclusions using multiplex assays to define sensitization for waitlisted candidates. We aimed to assess the impact of this change and review access to transplantation for highly sensitized patients under the current allocation rules. METHODS: Registry data were used to reconstruct changes in panel reactive antibody (PRA)/cPRA for all patients active on the waiting list between 2013 and 2018. A multilevel, mixed-effects negative binomial regression model was used to determine the association between sensitization and transplantation rate in the cPRA era. RESULTS: Following the introduction of cPRA, there was an increase in the percentage of the waiting list classified as highly sensitized (PRA/cPRA ≥80%) from 7.2% to 27.8% and very highly sensitized (PRA/cPRA ≥99%) from 2.7% to 15.3%. Any degree of sensitization was associated with a decreased rate of transplantation with a marked reduction for those with cPRA 95%-98% (adjusted incidence rate ratio, 0.36 [95% confidence interval, 0.28-0.47], P < 0.001) and cPRA ≥99% (adjusted incidence rate ratio, 0.09 [95% confidence interval, 0.07-0.12], P < 0.001). CONCLUSIONS: The proportion of the waiting list classified as highly sensitized increased substantially following the introduction of cPRA, and despite current prioritization, very highly sensitized patients have markedly reduced access to deceased donor transplantation.


Assuntos
Antígenos HLA/imunologia , Teste de Histocompatibilidade , Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim , Doadores de Tecidos/provisão & distribuição , Listas de Espera , Adulto , Austrália , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Acesso aos Serviços de Saúde , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
10.
Transfusion ; 61(8): 2255-2264, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34002408

RESUMO

BACKGROUND: Patients with sickle cell disease (SCD) are frequent recipients of red blood cell (RBC) transfusions and are at risk for RBC alloimmunization. RBC alloimmunization is diagnosed by identifying RBC alloantibodies as part of pre-transfusion testing, but this testing fails to detect alloantibodies that have evanesced. It may be beneficial to screen for new RBC alloantibody development after transfusion before possible antibody evanescence. STUDY DESIGN AND METHODS: Our institution started a new initiative for episodically transfused patients with SCD to obtain at least one antibody screen 2-6 months after transfusion as part of their clinical care. A database was created to prospectively track all transfused patients for 1 year and their post-transfusion antibody screen results. Patients received prophylactically CEK-matched RBC units. RESULTS: During the study year, 138 patients with SCD received a total of 242 RBC transfusions. Patients with a history of an RBC alloantibody (n = 13, 9.4%) had previously received more RBC units than non alloimmunized patients (median 11 vs. 2 RBC units, p = .0002). A total of 337 post-transfusion antibody screens were obtained in 127 patients (92.0%) with 110 patients (79.7%) having at least one antibody screen 2-6 months post-transfusion. With this prospective testing, two new RBC alloantibodies (anti-C and -M) were identified in two patients. CONCLUSION: It is feasible to test for new RBC alloantibody development in most episodically transfused patients with SCD as part of their routine care. The yield of this screening appears low with CEK matching, but it could still provide important information for individual patients.


Assuntos
Anemia Falciforme/terapia , Transfusão de Eritrócitos , Eritrócitos/imunologia , Isoanticorpos/imunologia , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/imunologia , Criança , Pré-Escolar , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/métodos , Feminino , Humanos , Isoanticorpos/sangue , Masculino , Estudos Prospectivos
11.
PLoS One ; 16(4): e0249934, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33886604

RESUMO

De novo donor-specific antibodies (dnDSA) are associated with antibody-mediated rejection (ABMR) and allograft loss. We tested Immucor* (IM) Luminex Single-antigen beads (LSAB) assay and C3d-fixing antibodies in the setting of dnDSA and subclinical (s) ABMR. This retrospective multicentric study included 123 patients biopsied because of the presence of subclinical de novo DSA detected by One Lamda* Labscreen (MFI > 1000). In 112 patients, sera of the day of the biopsy were available and tested in a central lab with IM Lifecodes LSAB and C3d fixing antibodies assays. In 16 patients (14.3%), no DSA was detected using Immucor test. In 96 patients, at least one DSA was determined with IM. Systematic biopsies showed active sABMR in 30 patients (31.2%), chronic active sABMR in 17 patients (17.7%) and no lesions of sABMR in 49 KT recipients (51%). Intensitity criteria (BCM, BCR and AD-BCR) of DSA were not statistically different between these 3 histological groups. The proportion of patients with C3d-fixing DSA was not statistically different between the 3 groups and did not offer any prognostic value regarding graft survival. Performing biopsy for dnDSA could not be guided by the intensity criteria of IM LSAB assay. C3d-fixing DSA do not offer added value.


Assuntos
Complemento C3d/imunologia , Rejeição de Enxerto/diagnóstico , Isoanticorpos/sangue , Transplante de Rim/efeitos adversos , Adulto , Biomarcadores/sangue , Feminino , França , Rejeição de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
12.
Hum Immunol ; 82(8): 568-573, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33910707

RESUMO

HLA antibodies are typically produced after exposure to transplanted tissue, pregnancy, and blood products. Sensitization delays access to transplantation and preclude utilization of donor organs. Infections and vaccinations have also been reported to result in HLA antibody formation. It is not known if patients develop HLA antibodies after infection with SARS-CoV-2. Here we analyzed a series of eighteen patients waiting for kidney transplantation who had symptomatic COVID-19 disease and recovered. None of the patients in this initial series developed de novo HLA antibodies. Notably, there was no increase in preexisting HLA antibodies in four highly sensitized patients with a CPRA > 80%. These preliminary data suggest that there may not be a need to repeat HLA antibody testing or perform a physical crossmatch on admission serum before kidney transplant for COVID-19 recovered patients. Data from a large number of patients with different demographics needed.


Assuntos
COVID-19/imunologia , Antígenos HLA/imunologia , Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim , SARS-CoV-2/imunologia , Listas de Espera , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/terapia , COVID-19/virologia , Bases de Dados Factuais , Feminino , Teste de Histocompatibilidade , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/patogenicidade
13.
Transfusion ; 61(6): 1972-1979, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33811650

RESUMO

BACKGROUND: Red blood cell alloimmunization is the first cause of fetal and neonatal anemia. Alloimmunizations with anti-PP1Pk or anti-P can cause recurrent miscarriages and hemolytic disease of the fetus and newborn in the 2nd and 3rd trimesters of pregnancy. We report on a pregnant patient immunized with anti-P and a history of recurrent miscarriages. CASE REPORT: This P2 k (GLOB:-1; P1PK:-1,3) patient had a first pregnancy marked by a caesarean at 38 weeks of gestation (WG) for non-reassuring fetal heart rate. Then, she had three early spontaneous miscarriages. The fifth pregnancy began with a high titer of anti-P at 128. Early initiation of treatment with Intravenous Immunoglobulins (IVIg) and plasma exchanges (PE) starting at 5 WG permitted us to reduce the titer of anti-P below 32. A healthy infant was delivered by caesarean at 38 WG without anemia at birth and no exchange transfusion was required. DISCUSSION AND REVIEW OF THE LITERATURE: The P and Pk antigens are expressed on placental, trophoblastic, and embryonic cells. This explains why P1 k (GLOB:-1; P1PK:1,3), P2 k (GLOB:-1; P1PK:-1,3), or Tj(a-)/p (GLOB:-1; P1PK:-1,-3) patients are prone to recurrent abortions in the first trimester of pregnancy. A literature review demonstrated 87% (68/78) of miscarriages in p patients. However, publication biases are possible with the most severe cases being reported. CONCLUSION: Immunizations to P and PP1Pk antigens differ from others in their physiopathology and precocity. The association of PE and IVIg seems to be an effective treatment in the management of anti-PP1Pk or anti-P fetomaternal incompatibilities.


Assuntos
Aborto Habitual/sangue , Isoanticorpos/sangue , Sistema do Grupo Sanguíneo P/sangue , Aborto Habitual/imunologia , Adulto , Eritroblastose Fetal/sangue , Eritroblastose Fetal/imunologia , Feminino , Humanos , Isoanticorpos/imunologia , N-Acetilgalactosaminiltransferases/sangue , N-Acetilgalactosaminiltransferases/imunologia , Sistema do Grupo Sanguíneo P/imunologia , Gravidez
16.
Front Immunol ; 12: 629608, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777014

RESUMO

Red blood cells expressing alloantigens are well known to be capable of inducing robust humoral alloantibody responses both in transfusion and pregnancy. However, the majority of transfusion recipients and pregnant women never make alloantibodies, even after repeat exposure to foreign RBCs. More recently, RBCs have been used as a cellular therapeutic-very much like transfusion, engineered RBCs are highly immunogenic in some cases but not others. In animal models of both transfusion and RBC based therapeutics, RBCs that do not induce an immune response also cause tolerance. Despite a robust phenomenology, the mechanisms of what regulates immunity vs. tolerance to RBCs remains unclear. However, it has been reported that copy number of alloantigens on the RBCs is a critical factor, with a very low copy number causing non-responsiveness (in both humans and mice) and also leading to tolerance in mice. Recently, we reported that an IgG2c specific for an RBC antigen can substantially enhance the humoral immune response upon transfusion of RBCs expressing that antigen. Herein, we report that an IgG2c converts RBCs with low antigen copy number from a tolerogenic to an immunogenic stimulus. These findings report the first known stimulus that induces humoral alloimmunization to a low copy number RBC alloantigen and identify a previously undescribed molecular switch that has the ability to affect responder vs. non-responder phenotypes of transfusion recipients.


Assuntos
Transfusão de Eritrócitos/efeitos adversos , Eritrócitos/imunologia , Dosagem de Genes , Tolerância Imunológica , Imunidade Humoral , Imunoglobulina G/imunologia , Isoanticorpos/imunologia , Isoantígenos/genética , Isoantígenos/imunologia , Animais , Variações do Número de Cópias de DNA , Epitopos , Feminino , Imunoglobulina G/sangue , Isoanticorpos/sangue , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
17.
Front Immunol ; 12: 634368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717174

RESUMO

Immunological rejection is an important factor resulting in allograft dysfunction, and more valid therapeutic methods need to be explored to improve allograft outcomes. Many researches have indicated that artemisinin and its derivative exhibits immunosuppressive functions, apart from serving as a traditional anti-malarial drug. In this assay, we further explored the therapeutic effects of artemisinin for transplant rejection in a rat cardiac transplantation model. We found that it markedly attenuated allograft rejection and histological injury and significantly prolonged the survival of allograft. Upon further exploring the mechanism, we demonstrated that artemisinin not only attenuated T cell-mediated rejection (TCMR) by reducing effector T cell infiltration and inflammatory cytokine secretion and increasing regulatory T cell infiltration and immunoregulatory cytokine levels, but also attenuated antibody-mediated rejection (ABMR) through inhibition of B cells activation and antibody production. Furthermore, artemisinin also reduced macrophage infiltration in allografts, which was determined to be important for TCMR and ABMR. Moreover, we demonstrated that artemisinin significantly inhibited the function of pure T cells, B cells, and macrophages in vitro. All in all, this study provide evidence that artemisinin significantly attenuates TCMR and ABMR by targeting multiple effectors. Therefore, this agent might have potential for use in clinical settings to protect against transplant rejection.


Assuntos
Artemisininas/farmacologia , Linfócitos B/efeitos dos fármacos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Coração/efeitos adversos , Imunossupressores/farmacologia , Transplante de Pele/efeitos adversos , Linfócitos T/efeitos dos fármacos , Adolescente , Adulto , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Células Cultivadas , Quimiotaxia de Leucócito/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Humanos , Isoanticorpos/sangue , Ativação Linfocitária/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Fenótipo , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fatores de Tempo , Adulto Jovem
18.
Transfusion ; 61(7): 2019-2024, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33745158

RESUMO

Disparities are prevalent in numerous areas of healthcare. We sought to investigate whether there were racial/ethnic disparities among pregnant women with the most severe form of alloimmunization who require intrauterine transfusions (IUT). We reviewed patients who underwent IUT for alloimmunization at a single fetal treatment center between 2015 and 2020. This "IUT cohort" was compared to an "Alloimmunization cohort": patients seen at our institution with a diagnosis of alloimmunization during pregnancy, who did not receive IUT. We collected maternal demographics including self-identified race/ethnicity and primary language, transfusion, and antibody characteristics. The cohorts were compared using unpaired t-tests, Mann-Whitney tests, and Fischer's exact tests, as appropriate. The IUT cohort included 43 patients and the alloimmunization cohort included 1049 patients. Compared to the alloimmunization cohort, there were significantly more patients of Latina descent in the IUT cohort (23.3% vs. 3.4%, p < .0001), and more non-English speakers (18.6% vs. 4.6%, p = .001). Twenty-one percent (9/43) of patients had immigrated to the United States, all of whom had pregnancies or miscarriages in their country of origin. A third of patients had new antibodies identified on serial screens during the current pregnancy. Significantly more women of Latina ethnicity and non-English speakers required IUTs compared to the cohort of women with alloimmunization. Insufficient access to care prior to arriving in the United States and among racial and ethnic minorities in the United States may contribute to these findings. Providers should be cognizant of potential, racial, and ethnic inequalities among women receiving intrauterine transfusions.


Assuntos
Transfusão de Sangue Intrauterina/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Histocompatibilidade Materno-Fetal/imunologia , Troca Materno-Fetal/imunologia , Aborto Espontâneo/etnologia , Adulto , Estudos de Coortes , Grupos de Populações Continentais/estatística & dados numéricos , Conjuntos de Dados como Assunto , Emigrantes e Imigrantes/estatística & dados numéricos , Grupos Étnicos/estatística & dados numéricos , Feminino , Disparidades em Assistência à Saúde/estatística & dados numéricos , Hispano-Americanos/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Humanos , Imunoglobulina G/imunologia , Isoanticorpos/sangue , Isoanticorpos/imunologia , Paridade , Gravidez , Imunoglobulina rho(D)/sangue , São Francisco , Classe Social
20.
Transfusion ; 61(4): 1336-1340, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33666248

RESUMO

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a transfusion complication often mediated by recipient exposure to plasma from donors with human leukocyte antigen (HLA) and human neutrophil antigen (HNA) antibodies. Recipient anti-donor HLA or HNA antibodies have rarely been implicated. STUDY DESIGN AND METHODS: Herein, we describe a case of fatal TRALI mediated by recipient anti-HLA and anti-HNA antibodies. Cognate antibody-antigen match was confirmed with serologic and molecular assays. RESULTS: A 69-year-old G5P5 female with no prior transfusion history and metastatic cholangiocarcinoma with thromboembolic complications presented with heart failure and dyspnea. She was transfused 15 ml of a unit of Fya -negative red blood cells and subsequently developed acute onset dyspnea, hypoxemia, hypotension, and fever. Clinical investigations revealed bilateral infiltrates on chest X-ray and cognate recipient HLA and HNA antibodies to donor antigens. The patient died of acute respiratory failure within 24 h of transfusion. In total, the patient had Fya , HLA Class I, HNA, and human platelet antigen (HPA) alloantibodies. The 63-year-old female donor had detectable HLA class II antibodies (recipient class II genotype unavailable). CONCLUSION: The pathophysiology of TRALI has traditionally been ascribed to underlying conditions that put the recipient at risk in combination with donor biological response modifiers. This case illustrates alternative pathogenic mediators including alloantibodies to donor HLA and HNA. Additional studies to determine the contribution and frequency of recipient alloantibodies in TRALI may inform future mitigation strategies to further reduce the incidence of TRALI, particularly in female transfusion recipients.


Assuntos
Colangiocarcinoma/secundário , Antígenos HLA/imunologia , Neutrófilos/imunologia , Lesão Pulmonar Aguda Relacionada à Transfusão/diagnóstico , Idoso , Doadores de Sangue , Colangiocarcinoma/complicações , Dispneia/etiologia , Evolução Fatal , Feminino , Febre/etiologia , Humanos , Hipotensão/etiologia , Hipóxia/etiologia , Isoanticorpos/sangue , Pessoa de Meia-Idade , Plasma/imunologia , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Tromboembolia/etiologia , Reação Transfusional/complicações , Lesão Pulmonar Aguda Relacionada à Transfusão/complicações , Lesão Pulmonar Aguda Relacionada à Transfusão/imunologia , Lesão Pulmonar Aguda Relacionada à Transfusão/fisiopatologia , Transplantados
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