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2.
Ann Hematol ; 100(10): 2463-2469, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34324022

RESUMO

Alloimmunization is a serious complication in ß-thalassemia major patients as a result of repeated blood transfusion. The immune checkpoint receptors play an important role in regulating immune system homeostasis and the function of the immune cells. This study aimed to evaluate the expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) immune checkpoint molecules in ß-thalassemia major patients with and without alloantibody. For this purpose, 68 ß-thalassemia major patients with (34 patients) and without (34 patients) alloantibody as well as 20 healthy controls were enrolled. The expression of these genes was evaluated in different groups of patients by SYBR Green real-time PCR method. Our results showed that the mean expression of LAG-3 was significantly increased in thalassemia patients compared to the control group (*P < 0.001). However, there was no significant difference in expression of the CTLA-4 and TIM-3 as well as LAG-3 genes between patients with and without alloantibody (P > 0.05). A positive correlation was observed between the level of LAG-3 expression with markers associated with Treg function including FOXP3 and GDF-15 genes in ß-thalassemia major patients. Taken together, the LAG-3 molecule might have a more prominent role in the abnormality of the immune system in thalassemia patients especially the function of regulatory T cells (Tregs), prior to the CTLA-4 and TIM-3 genes.


Assuntos
Antígenos CD/genética , Antígeno CTLA-4/genética , Receptor Celular 2 do Vírus da Hepatite A/genética , Talassemia beta/genética , Adolescente , Adulto , Antígenos CD/imunologia , Antígeno CTLA-4/imunologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Isoanticorpos/imunologia , Masculino , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Adulto Jovem , Talassemia beta/imunologia
3.
Clin Immunol ; 229: 108792, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34217849

RESUMO

This study evaluate the potential of plasmatic CXCL-10 (pCXCL-10) as a pre&post transplantation prognostic and diagnostic biomarker of T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR) and subclinical rejection (SCR) risk in adult kidney recipients considering BKV and CMV infections as possible clinical confounder factors. Twenty-eight of 100 patients included experienced rejection (TCMR:14; ABMR:14); 8 SCR; 13 and 16 were diagnosed with BKV and CMV infection, respectively. Pre-transplantation pCXCL-10 was significantly increased in TCMR and ABMR and post-transplantation in TCMR, ABMR and SCR compared with nonrejectors. All CMV+ patients showed pCXCL-10 levels above the cutoff values established for rejection whereas the 80% of BKV+ patients showed pCXCL-10 concentration < 100 pg/mL. pCXCL-10 could improve pre-transplantation patient stratification and immunosuppressive treatment selection according to rejection risk; and after kidney transplantation could be a potential early prognostic biomarker for rejection. Clinical confounding factor in BKV+ and particularly in CMV+ patients must be discarded.


Assuntos
Quimiocina CXCL10/sangue , Rejeição de Enxerto/sangue , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Adulto , Idoso , Vírus BK , Biomarcadores/sangue , Quimiocina CXCL10/urina , Infecções por Citomegalovirus/complicações , Feminino , Rejeição de Enxerto/etiologia , Humanos , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/complicações , Prognóstico , Estudos Prospectivos , Fatores de Risco , Linfócitos T/imunologia , Infecções Tumorais por Vírus/complicações
5.
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
6.
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
8.
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
9.
Front Immunol ; 12: 657894, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135891

RESUMO

We aimed to investigate the mechanisms of humoral immune activation in ABMR using a MHC-mismatched rat kidney transplant model. We applied low dose cyclosporine A (loCNI) to allow donor-specific antibody (DSA) formation and rejection and high dose cyclosporine A (hiCNI) for non-rejection. DSA and leukocyte subsets were measured by flow cytometry. Germinal centers (GC), T follicular helper cells (Tfh), plasma cells and interleukin-21 (IL-21) expression were analyzed by immunofluorescence microscopy. Expression of important costimulatory molecules and cytokines was measured by qRT-PCR. Allograft rejection was evaluated by a nephropathologist. We found that DSA formation correlated with GC frequency and expansion, and that GC size was linked to the number of activated Tfh. In hiCNI, GC and activated Tfh were virtually absent, resulting in fewer plasma cells and no DSA or ABMR. Expression of B cell activating T cell cytokine IL-21 was substantially inhibited in hiCNI, but not in loCNI. In addition, hiCNI showed lower expression of ICOS ligand and IL-6, which stimulate Tfh differentiation and maintenance. Overall, Tfh:B cell crosstalk was controlled only by hiCNI treatment, preventing the development of DSA and ABMR. Additional strategies targeting Tfh:B cell interactions are needed for preventing alloantibody formation and ABMR.


Assuntos
Linfócitos B/imunologia , Comunicação Celular , Rejeição de Enxerto/imunologia , Isoanticorpos/imunologia , Transplante de Rim/efeitos adversos , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Linfócitos B/metabolismo , Biomarcadores , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/farmacologia , Comunicação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Citocinas/metabolismo , Fibrose , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Rejeição de Enxerto/metabolismo , Imunidade Humoral , Imuno-Histoquímica , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Modelos Animais , Ratos , Linfócitos T Auxiliares-Indutores/metabolismo
12.
Transfusion ; 61(7): 2169-2178, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34181769

RESUMO

BACKGROUND: Despite the significant adverse clinical consequences of RBC alloimmunization, our understanding of the signals that induce immune responses to transfused RBCs remains incomplete. Though RBC storage has been shown to enhance alloimmunization in the hen egg lysozyme, ovalbumin, and human Duffy (HOD) RBC alloantigen mouse model, the molecular signals leading to immune activation in this system remain unclear. Given that the nonclassical major histocompatibility complex (MHC) Class I molecule CD1D can bind to multiple different lysophospholipids and direct immune activation, we hypothesized that storage of RBCs increases lysophospholipids known to bind CD1D, and further that recipient CD1D recognition of these altered lipids mediates storage-induced alloimmunization responses. STUDY DESIGN AND METHODS: We used a mass spectrometry-based approach to analyze the changes in lysophospholipids that are induced during storage of mouse RBCs. CD1D knockout (CD1D-KO) and wild-type (WT) control mice were transfused with stored HOD RBCs to measure the impact of CD1D deficiency on RBC alloimmunization. RESULTS: RBC storage results in alterations in multiple lysophospholipid species known to bind to CD1D and activate the immune system. Prior to transfusion, CD1D-deficient mice had lower baseline levels of polyclonal immunoglobulin (IgG) relative to WT mice. In response to stored RBC transfusion, CD1D-deficient mice generated similar levels of anti-HOD IgM and anti-HOD IgG. CONCLUSION: Although storage of RBCs leads to alteration of several lysophospholipids known to be capable of binding CD1D, storage-induced RBC alloimmunization responses are not impacted by recipient CD1D deficiency.


Assuntos
Antígenos CD1d/imunologia , Preservação de Sangue , Transfusão de Sangue , Eritrócitos/imunologia , Isoanticorpos/biossíntese , Isoantígenos/imunologia , Lisofosfolipídeos/sangue , Reação Transfusional/imunologia , Alarminas/sangue , Alarminas/imunologia , Animais , Especificidade de Anticorpos , Antígenos CD1d/genética , Antígenos CD1d/metabolismo , Sistema do Grupo Sanguíneo Duffy/genética , Sistema do Grupo Sanguíneo Duffy/imunologia , Feminino , Imunização , Imunoglobulina G/biossíntese , Imunoglobulina G/imunologia , Imunoglobulina M/biossíntese , Imunoglobulina M/imunologia , Isoanticorpos/imunologia , Lisofosfolipídeos/metabolismo , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Camundongos Transgênicos , Muramidase/imunologia , Ovalbumina/imunologia , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia
13.
Transfusion ; 61(8): 2458-2467, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34121200

RESUMO

BACKGROUND: Red blood cell (RBC) alloimmunization is a complication of patients with sickle cell disease (SCD) and it has a greater impact on pregnancy, leading to a risk of hemolytic disease of the newborn and reducing blood availability for pregnant women. This study proposed to evaluate antigen matching transfusion protocols, aiming to reduce RBC alloimmunization in Brazilian female patients with SCD. METHODS: Samples from female patients with SCD (153) and self-declared Afro-Brazilian donors (307) were genotyped for RBC antigens and RH variants were investigated. The transfusion needs of patients during 1-year period and the number of compatible donors were assessed using three antigen-matching transfusion protocols: prophylactic CEK antigen-matched RBCs, prophylactic extended antigen-matched RBCs, and extended-matched red blood cells (RBCs) only for alloimmunized patients. In addition, RH molecular matching has been proposed for patients carrying variant RHCE. RESULTS: Provision of CEK antigen-matched donors would have been possible in 92.4% of transfusion events while provision of prophylactic extended antigen-matched RBCs would cover 88.7% of the transfusion events. Extended antigen matching for alloimmunized patients would be efficient in 99% of the cases. The presence of partial D in 10 patients increased the need of D-negative donors. Compatible donors could be enough for four of the five patients with altered RHCE genotypes in both alleles. CONCLUSION: In Brazilians, screening African descent donors allows the implementation of prophylactic CEK and extended antigen-matching transfusion protocols to female patients with SCD to reduce RBC alloimmunization; however, the supply of compatible blood can be impaired for patients with Rh variants.


Assuntos
Anemia Falciforme/terapia , Transfusão de Eritrócitos/métodos , Eritrócitos/imunologia , Adulto , Anemia Falciforme/imunologia , Doadores de Sangue , Tipagem e Reações Cruzadas Sanguíneas , Brasil , Transfusão de Eritrócitos/efeitos adversos , Feminino , Humanos , Isoanticorpos/imunologia , Pessoa de Meia-Idade , Adulto Jovem
14.
Pan Afr Med J ; 38: 304, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34178222

RESUMO

Blood transfusion is a medical procedure used to treat patients with labile blood product. Each transfusion of globular concentrate exposes recipients to the risk of red blood cell alloimmunization. The test for red cell antibodies (RCA) ensures the immunohaematological safety of transfused patients. In Benin, this test is not performed in a systematic way or included either in the pre-transfusion or in the post-transfusion tests. The purpose of this study is to determine the presence of red cell antibodies among polytransfused patients. RCA was performed using indirect antiglobulin test on gel-filtration in 51 polytransfused patients including 26 selected in the Department of Hematology and 25 in the Department of Nephrology at the National Hospital and University Center of Cotonou. After phenotyping alloimmunized patients, tests for detecting signs of hemolysis were performed. Clinical data as well as those on transfusion were collected from transfusion registries and medical records. The prevalence of alloimmunization in our study population was 13.73%. The antibodies identified had the following characteristics: association of anti-RH1 and anti-RH3, anti LE1, association of anti-RH3 and anti-FY1. Alloantibodies were more frequent in patients who had received more than 15 packed red blood cells. Laboratory tests showed signs of hemolysis in one alloimmunized patient. There was no correlation between age, sex, clinical diagnosis and the occurrence of red blood cell alloimmunization. The test for red cell antibodies should be systematically performed in polytransfused patients in order to ensure better transfusion recipient safety in Benin.


Assuntos
Transfusão de Sangue , Eritrócitos/imunologia , Hemólise/imunologia , Isoanticorpos/imunologia , Adulto , Benin , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
15.
Br J Haematol ; 193(5): 961-970, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33954989

RESUMO

Descriptions of passenger lymphocyte syndrome (PLS), immune cytopenias and transplant-associated thrombotic microangiopathy (TA-TMA) after intestine-containing transplants remain scarce. We describe our centre's experience of these complications from 2007 to 2019. Ninety-six patients received 103 transplants. PLS occurred in 9 (9%) patients (median 12 days post-transplant); all due to ABO antibodies. There were 31 minor ABO mismatch transplants. No patient required change in immunosuppression. Immune cytopenias (excluding PLS) occurred in six patients at an incidence of 1·7/100 patient years; three immune haemolysis, one immune thrombocytopenia, one acquired Glanzmann's and one immune neutropenia; 50% occurred with other cytopenias. All cases eventually responded to treatment, with a median of four treatments (range 1-8) and 5/6 were treated with rituximab. One patient with immune haemolysis required bortezomib. Complications were common in patients with immune cytopenias; 4/6 with infection needing intravenous antibiotics and 3/6 with venous thromboembolism. In 3/6 cases, a secondary cause for the immune cytopenia was evident. Switching from tacrolimus to ciclosporin was not necessary. There were five cases of transplant-associated thrombotic microangiopathy (TA-TMA; 1·5/100 patient years) requiring calcineurin inhibitor withdrawal; two cases associated with acute rejection. Two cases were managed with plasma exchange, one with plasma infusions and one with eculizumab. Further research in this patient group is required.


Assuntos
Hemólise/imunologia , Intestinos/transplante , Neutropenia , Transplante de Órgãos/efeitos adversos , Trombastenia , Microangiopatias Trombóticas , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Bortezomib/administração & dosagem , Feminino , Seguimentos , Humanos , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Neutropenia/tratamento farmacológico , Neutropenia/etiologia , Neutropenia/imunologia , Estudos Retrospectivos , Rituximab/administração & dosagem , Trombastenia/tratamento farmacológico , Trombastenia/etiologia , Trombastenia/imunologia , Microangiopatias Trombóticas/tratamento farmacológico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/imunologia
16.
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
17.
Transfusion ; 61(6): 1908-1915, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33938570

RESUMO

BACKGROUND: The anti-M antibody can lead to hemolytic disease of the fetus and newborn (HDFN) and adverse fetal outcomes, especially in the Asian population. However, fetal erythropoiesis resulting from M alloimmunization needs further investigation. STUDY DESIGN AND METHODS: We analyzed erythropoiesis in eight fetuses with M alloimmunization and compared them with the fetuses affected by anti-D. They were matched as pairs according to the gestational age of diagnosis and the hematocrit before treatment. Paired t-tests or paired Wilcoxon rank-sum tests were conducted to compare the difference in the cord blood indexes. Pearson correlation analysis was used to evaluate the correlativity between hematocrit and the reticulocyte percentage in the two groups. RESULTS: The fetuses in the MN group had lower reticulocyte count and percentage than those in the RhD group (p < .05). All of the fetal reticulocyte production indexes (RPIs) in the MN group were less than 2, indicating an inadequate hemopoietic response to anemia, while the majority of the RPIs in the RhD group (85.7%) were significantly higher (p = .003), with 6 cases greater than 2.5. Hematocrit was negatively correlated with reticulocyte percentage (y = 54.7-171.7x, r2  = 0.825, p = .005) in the RhD group, while no significant correlation was found in the MN group. No difference in the number of IUT, interval, or the fetal outcome was found between the two groups. CONCLUSION: Fetal reticulocytopenia provided direct evidence of an inadequate hemopoietic response in HDFN due to anti-M, leading to hyporegenerative anemia. Once the IgG component of anti-M is detected, close monitoring should be considered.


Assuntos
Anemia/imunologia , Eritroblastose Fetal/imunologia , Feto/imunologia , Imunoglobulina M/imunologia , Isoanticorpos/imunologia , Adulto , Anemia/etiologia , Anemia/fisiopatologia , Anemia/terapia , Transfusão de Sangue Intrauterina , Eritroblastose Fetal/fisiopatologia , Eritroblastose Fetal/terapia , Eritropoese , Feminino , Feto/fisiopatologia , Humanos , Recém-Nascido , Masculino , Gravidez , Reticulocitose , Imunoglobulina rho(D)/imunologia , Resultado do Tratamento , Adulto Jovem
18.
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
19.
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
20.
Front Immunol ; 12: 657217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859649

RESUMO

During pregnancy the formation of alloreactive anti-human leukocyte antigen (HLA) antibodies are a major cause of acute rejection in organ transplantation and of adverse effects in blood transfusion. The purpose of the study was to identify maternal HLA class Ib genetic factors associated with anti-HLA allo-immunization in pregnancy and the degree of tolerance estimated by IgG4 expression. In total, 86 primiparous women with singleton pregnancies were included in the study. Maternal blood samples and umbilical cord samples were collected at delivery. Clinical data were obtained. Maternal blood serum was screened for HLA class I and II antibodies, identification of Donor Specific Antibody (DSA), activation of complement measured by C1q and IgG4 concentrations. Mothers were genotyped for HLA class Ib (HLA-E, -F and -G). Anti-HLA class I and II antibodies were identified in 24% of the women. The maternal HLA-E*01:06 allele was significantly associated with a higher fraction of anti-HLA I immunization (20.0% vs. 4.8%, p = 0.048). The maternal HLA-G 3'-untranslated region UTR4-HLA-G*01:01:01:05 haplotype and the HLA-F*01:03:01 allele were significantly associated with a low anti-HLA I C1q activation (16.7% vs. 57.1%, p = 0.028; 16.7% vs. 50.0%, p = 0.046; respectively). Both HLA­G and HLA-F*01:03:01 showed significantly higher levels of IgG4 compared with the other haplotypes. The results support an association of certain HLA class Ib alleles with allo-immunization during pregnancy. Further studies are needed to elucidate the roles of HLA-E*01:06, HLA-F*01:03 and HLA­G UTR4 in reducing the risk for allo-immunization.


Assuntos
Antígenos HLA-DQ/genética , Antígenos HLA-DQ/imunologia , Isoanticorpos/imunologia , Polimorfismo Genético , Adolescente , Adulto , Alelos , Feminino , Dosagem de Genes , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Imunização , Imunoglobulina G/imunologia , Fenótipo , Gravidez , Adulto Jovem
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