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1.
Ann Hematol ; 99(3): 421-429, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31984437

RESUMO

ß-thalassemia major is one of the most common hematologic disorders in the world. It causes severe anemia and patients require regular blood transfusions, which causes different complications such as iron overload and alloimmunization. Regulatory T cells (Tregs) have an important role in regulation of immune responses. FoxP3 is the major marker of Tregs and its expression can be influenced by different factors. GDF-15 is another gene that plays a role in iron homeostasis and regulation of immune system in different diseases. The aim of this study was to assess the frequency of Tregs and FoxP3/GDF-15 gene expression in ß-thalassemia major patients with and without alloantibody as well as its correlation with different factors such as serum ferritin and folate levels. This study was conducted on 68 ß-thalassemia major patients with and without alloantibodies in comparison with 20 healthy individuals with matched age and sex as control group. Enzyme-linked immunosorbent assay (ELISA), flow cytometry, and real-time PCR were performed in order to evaluate serum ferritin and folate levels, frequency of Tregs, and the expression of FoxP3 and GDF-15 genes, respectively. The percentage and absolute count of Tregs were increased in patients compared with controls (P = 0.0003), but there was no difference between responders and non-responders (P > 0.05). The Tregs count correlated positively with serum ferritin. No correlation was observed between target genes and serum ferritin and folate, but there was a positive significant correlation between the expression of FoxP3 and GDF-15 genes, which shows the immunosuppressive role of GDF-15.


Assuntos
Ferritinas , Ácido Fólico , Fatores de Transcrição Forkhead , Regulação da Expressão Gênica/imunologia , Fator 15 de Diferenciação de Crescimento , Isoanticorpos , Linfócitos T Reguladores , Talassemia beta , Adolescente , Adulto , Criança , Feminino , Ferritinas/sangue , Ferritinas/imunologia , Ácido Fólico/sangue , Ácido Fólico/imunologia , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/imunologia , Fator 15 de Diferenciação de Crescimento/biossíntese , Fator 15 de Diferenciação de Crescimento/imunologia , Humanos , Isoanticorpos/sangue , Isoanticorpos/imunologia , Masculino , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Talassemia beta/sangue , Talassemia beta/imunologia , Talassemia beta/patologia
2.
Ren Fail ; 42(1): 40-47, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31875761

RESUMO

Background: De novo Donor Specific Antibodies (DSA) are considered as a risk factor for the kidney allograft outcomes in recipients after simultaneous liver-kidney transplantation (SLKT). We hypothesized that length of hospital stay (LOS) might be associated with de novo DSA development of due to the increased likelihood of receiving blood transfusions with reduced immunosuppressive regimens.Methods: This study is a single-center, retrospective cohort study consisting of 85 recipients who underwent SLKT from 2009 to 2018 in our hospital. We divided the patients into two groups according to LOS [long hospital stay (L) group (LOS >14 days) and short hospital stay (S) group (LOS ≤14 days)]. Propensity score (PS) has been created using logistic regression to predict LOS greater than median of 14 days. The association between the presence of de novo DSA and LOS was assessed by logistic regression models adjusted for PS.Results: The mean age at transplantation of the entire cohort was 55.5 ± 10.1 years. Sixty percent of the recipients were male and Caucasian. Median LOS in (L) group was three-fold longer than (S) group [L: median 30 days (IQR: 21-52), S: median 8.5 days (IQR: 7-11)]. Eight patients developed de novo DSA after SLKT (9.4%), all of them were in (L) group. Longer LOS was significantly associated with higher risk of development of de novo DSA in unadjusted (OR+ each 5 days: 1.09, 95% CI:1.02-1.16) and PS adjusted (OR+ each 5 days: 1.11, 95% CI:1.02-1.21) analysis.Conclusion: Longer hospitalization is significantly associated with the development of de novo DSA in SLKT.


Assuntos
Rejeição de Enxerto/epidemiologia , Isoanticorpos/sangue , Transplante de Rim/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Transplante de Fígado/efeitos adversos , Adulto , Idoso , Aloenxertos/imunologia , Transfusão de Sangue/estatística & dados numéricos , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Incidência , Isoanticorpos/imunologia , Isoantígenos/imunologia , Rim/imunologia , Fígado/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
4.
Blood ; 134(24): 2127-2138, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31697801

RESUMO

Emicizumab, a bispecific humanized monoclonal antibody, bridges activated factor IX (FIX) and FX to restore the function of missing activated FVIII in hemophilia A. Emicizumab prophylaxis in children with hemophilia A and FVIII inhibitors was investigated in a phase 3 trial (HAVEN 2). Participants, previously receiving episodic/prophylactic bypassing agents (BPAs), were treated with subcutaneous emicizumab: 1.5 mg/kg weekly (group A), 3 mg/kg every 2 weeks (group B), or 6 mg/kg every 4 weeks (group C). Pharmacokinetics, safety, and efficacy (including an intraindividual comparison of participants from a noninterventional study) were evaluated. Eighty-five participants aged <12 years were enrolled. In group A (n = 65), the annualized rate of treated bleeding events (ABRs) was 0.3 (95% confidence interval [CI], 0.17-0.50), and 77% had no treated bleeding events. Intraindividual comparison of 15 participants who previously took BPA prophylaxis showed that emicizumab prophylaxis reduced the ABR by 99% (95% CI, 97.4-99.4). In groups B (n = 10) and C (n = 10), ABRs were 0.2 (95% CI, 0.03-1.72) and 2.2 (95% CI, 0.69-6.81), respectively. The most frequent adverse events were nasopharyngitis and injection-site reactions; no thrombotic events occurred. Two of 88 participants developed antidrug antibodies (ADAs) with neutralizing potential, that is, associated with decreased emicizumab plasma concentrations: 1 experienced loss of efficacy, and, in the other, ADAs disappeared over time without intervention or breakthrough bleeding. All other participants achieved effective emicizumab plasma concentrations, regardless of the treatment regimen. Emicizumab prophylaxis has been shown to be a highly effective novel medication for children with hemophilia A and inhibitors. This trial was registered at www.clinicaltrials.gov as #NCT02795767.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/prevenção & controle , Adolescente , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/farmacocinética , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Criança , Pré-Escolar , Fator VIII/antagonistas & inibidores , Fator VIII/imunologia , Feminino , Hemofilia A/imunologia , Humanos , Lactente , Isoanticorpos/sangue , Isoanticorpos/imunologia , Masculino , Qualidade de Vida , Resultado do Tratamento
5.
Blood ; 134(22): e1-e8, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31697836

RESUMO

Human platelet membrane glycoprotein polymorphisms can be immunogenic in man and are frequently the cause of clinically important immune reactions responsible for disorders such as neonatal alloimmune thrombocytopenia. Platelets from individuals carrying rare polymorphisms are often difficult to obtain, making diagnostic testing and transfusion of matched platelets challenging. In addition, class I HLA antibodies frequently present in maternal sera interfere with the detection of platelet-reactive alloantibodies. Detection of alloantibodies to human platelet antigen 3 (HPA-3) and HPA-9 is especially challenging, in part because of the presence of cell type-specific glycans situated near the polymorphic amino acid that together form the alloepitope. To overcome these limitations, we generated a series of HLA class I-negative blood group O induced pluripotent stem cell (iPSC) lines that were gene edited to sequentially convert their endogenous HPA-3a alloantigenic epitope to HPA-3b, and HPA-9a to HPA-9b. Subjecting these cell lines, upon differentiation into CD41+/CD42b+ human megakaryocytes (MKs), to flow cytometric detection of suspected anti-HPA-3 and HPA-9 alloantisera revealed that the HPA-3a-positive MKs specifically reacted with HPA-3a patient sera, whereas the HPA-3b MKs lost reactivity with HPA-3a patient sera while acquiring reactivity to HPA-3b patient sera. Importantly, HPA-9b-expressing MKs specifically reacted with anti-HPA-9b-suspected patient samples that had been undetectable using conventional techniques. The provision of specialized iPSC-derived human MKs expressing intact homozygous glycoprotein alloantigens on the cell surface that carry the appropriate endogenous carbohydrate moieties should greatly enhance detection of clinically important and rare HPA-specific alloantibodies that, to date, have resisted detection using current methods.


Assuntos
Antígenos de Plaquetas Humanas/imunologia , Engenharia Celular , Células-Tronco Pluripotentes Induzidas/imunologia , Isoanticorpos/imunologia , Megacariócitos/imunologia , Antígenos de Plaquetas Humanas/genética , Antígenos de Plaquetas Humanas/metabolismo , Citometria de Fluxo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Isoanticorpos/sangue , Megacariócitos/metabolismo
6.
Thromb Haemost ; 119(11): 1807-1815, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587244

RESUMO

BACKGROUND: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) results from maternal alloantibodies (abs) reacting with fetal platelets expressing paternal human platelet antigens (HPAs), mostly HPA-1a. Anti-HPA-1a abs, are the most frequent cause of severe thrombocytopenia and intracranial hemorrhage (ICH). OBJECTIVES: Titration of anti-HPA-1a in maternal serum using standard National Institute for Biological Standards and Control (NIBSC) 03/152 is one diagnostic approach to predict the severity of FNAIT. Recently, we found three anti-HPA-1a subtypes reacting with the ß3 subunit independently or dependently from complexes with αIIb and αv. Endothelial cell-reactive anti-αvß3 abs were found predominantly in cases with ICH. Our aim was to assess whether available standard material represents all anti-HPA-1a subtypes. MATERIALS AND METHODS: In this study, anti-HPA-1a sera (NIBSC 03/152) and human monoclonal antibodies (moabs) against HPA-1a (moabs 26.4 and 813) were evaluated using transfected cell lines expressing αIIbß3, αvß3 or monomeric cß3. RESULTS: Flow cytometry analyses with well-characterized murine moabs recognizing αIIbß3, αvß3, or ß3 alone demonstrated that AP3 reacts compound-independently, whereas compound-dependent moabs Gi5 and 23C6 reacted only with complexes. NIBSC 03/152, moabs 26.4, and 813 against HPA-1a reacted like AP3, same results were obtained with monomeric cß3 in immunoblotting. Antigen capture assay targeting endothelial cells showed anti-HPA-1a reactivity disappearance after cß3 beads adsorption. Furthermore, in contrast to anti-HPA-1a abs from ICH cases, none of NIBSC 03/152, 26.4, and 813 inhibited tube formation. CONCLUSION: These results suggest that current anti-HPA-1a standard material contains only the anti-ß3 subtype. The absence of anti-αvß3 makes NIBSC 03/152 less suitable as standard to predict the severity of FNAIT.


Assuntos
Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Antígenos de Plaquetas Humanas/imunologia , Testes Imunológicos , Integrina alfaVbeta3/imunologia , Integrina beta3/imunologia , Isoanticorpos/imunologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/imunologia , Trombocitopenia Neonatal Aloimune/diagnóstico , Células Endoteliais/imunologia , Células HEK293 , Humanos , Isoanticorpos/sangue , Neovascularização Fisiológica , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Trombocitopenia Neonatal Aloimune/sangue , Trombocitopenia Neonatal Aloimune/imunologia
7.
Transfus Med ; 29(6): 415-422, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31646705

RESUMO

OBJECTIVES: This study aimed to analyse the allele frequency of blood group antigens in the Korean population and other ethnic populations and the association of blood group antigens with red blood cell (RBC) alloantibodies. BACKGROUND: Blood group antigen genotyping can support patients undergoing frequent transfusions who have alloantibodies and antibodies against high-prevalence blood group antigens. METHODS: Twenty-nine single nucleotide variations and 37 blood group antigens were tested. Samples requested for routine blood typing were collected from Jan to Apr 2016. Genotyping was performed on 145 Korean samples and was confirmed by bidirectional sequencing and serologic tests. The allele frequency data were compared with previous genotyping datasets (three datasets from Korea and one each from China, Europe, Asia, and the USA). Alloantibody frequencies and blood group antigens from the electronic medical record of 1772 cases were examined. RESULTS: E antigen was higher in the Korean population compared to that of Asian and European populations. K, Kpa , Fyb and Doa allele frequencies were lower compared to other ethnic populations. RBC alloantibodies with frequencies (%) greater than 1% from the 1772 cases were as follows: anti-E, 36·7%, anti-C, 17·7%; anti-c 7·39%; anti-M, 5·9%; anti-e, 5·2%; anti-Jka , 2·9%; and anti-Fya , 1·1%. Blood group antigens and alloantibody frequencies revealed inverse trends that did not reach statistical significance. CONCLUSION: The allele frequency of blood group antigens assessed by high-throughput methods provided reliable and valuable information that could be used for maintaining donor pools and providing compatible blood for genotyped patients.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Antígenos de Grupos Sanguíneos , Tipagem e Reações Cruzadas Sanguíneas , Frequência do Gene , Genótipo , Isoanticorpos/sangue , Adulto , Antígenos de Grupos Sanguíneos/sangue , Antígenos de Grupos Sanguíneos/genética , Feminino , Humanos , Masculino , Prevalência , República da Coreia/etnologia
8.
Clin Exp Nephrol ; 23(12): 1398-1406, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31493185

RESUMO

BACKGROUND: We evaluated the impact of persistent preformed donor-specific antibody (DSA) and de novo DSA (dnDSA) detected at 1 year posttransplantation on long-term death-censored graft survival. METHODS: One hundred and sixty adult patients who received living kidney allograft with pretransplant-negative T-cell complement-dependent cytotoxicity crossmatch (CDCXM), and without periodic screening for DSA, were eligible for this study. All enrolled patients were retrospectively tested for DSA using the Luminex assay. The presence of DSA was analyzed in stored serum samples collected at 1 year posttransplantation. If the recipients had DSA, it was analyzed in the pretransplant serum sample. The detection of DSA solely in the 1 year posttransplant sample was defined as dnDSA, and DSA detection in both pretransplant and 1 year posttransplant samples was defined as persistent preformed DSA. RESULTS: DSAs were identified in 14 (8.8%) of the 160 patients. Seven patients had persistent preformed DSA, 6 had dnDSA, and 1 had both persistent preformed and dnDSA at 1 year posttransplantation. Death-censored allograft survival rates of patients with DSA versus those without DSA at 7 and 11 years were 77.9 vs. 97.8% and 60.6 vs. 89.2%, respectively. The graft survival rate was lower in patients with persistent preformed DSA and/or dnDSA. Each case of preformed DSA and dnDSA was associated with long-term graft survival. CONCLUSION: The presence of persistent preformed DSA or dnDSA at 1 year posttransplantation may be a predictor of long-term graft survival. Further study is needed to evaluate whether periodic screening for DSA improves long-term graft survival.


Assuntos
Sobrevivência de Enxerto , Antígenos HLA/imunologia , Isoanticorpos/sangue , Transplante de Rim , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Antígenos HLA/genética , Teste de Histocompatibilidade , Humanos , Japão , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
Transfus Apher Sci ; 58(5): 625-627, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31515172

RESUMO

GP.Mur antigen belongs to the MNSs system and the corresponding antibody is called as anti-Mia antibody. Anti-Mia antibody is a clinically significant antibody capable of causing haemolytic disease of the new born (HDFN) and intravascular haemolytic transfusion reactions. Literature on anti-Mia antibody from India is very limited. We report here a case of anti-Mia antibody in a multi-transfused patient from India.


Assuntos
Antígenos de Grupos Sanguíneos , Transfusão de Eritrócitos/efeitos adversos , Glicoforinas , Isoanticorpos , Talassemia beta , Adulto , Antígenos de Grupos Sanguíneos/sangue , Antígenos de Grupos Sanguíneos/imunologia , Glicoforinas/sangue , Glicoforinas/imunologia , Humanos , Índia , Isoanticorpos/sangue , Isoanticorpos/imunologia , Masculino , Talassemia beta/sangue , Talassemia beta/imunologia , Talassemia beta/terapia
10.
Tunis Med ; 97(2): 388-390, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31539100

RESUMO

The diagnosis and the treatment of rare phenotypes remain a problematic situation in many countries especially in Tunisia. Individuals with rare phenotype may develop clinically significant red cell antibodies directed against the high incidence Antigens they lack. A 35 years old patient was referred to our laboratory to explain a high incidence (twelve) of recurrent miscarriage during the first and second terms of pregnancy. This patient was grouped as O Rhesus: 1, -2, -3, 4, 5 K:-1. In her plasma we identified a pan-reactive anti-PP1PK antibody (anti-Tja) recognized to be responsible of spontaneous recurrent abortions. The red cell phenotype was P1 and Tja negative. More investigations concluded to the absence of auto and other allo-antibodies association. Therapeutic plasmapheresis from early stages was suggested for the future pregnancy to remove anti-public antibodies in order to maintain normal placenta functions. The Anti-Tja antibody, naturally occurring in patients with rare p phenotype, has the ability to induce recurrent spontaneous miscarriages and to cause immediate hemolytic transfusion reactions. Despite the absence of compatible donors in her family, this patient is not in an impasse situation because two donors with the same phenotype were identified when investigating a first case in 2013.


Assuntos
Aborto Habitual/diagnóstico , Aborto Habitual/imunologia , Isoanticorpos/efeitos adversos , Sistema do Grupo Sanguíneo P/imunologia , Aborto Habitual/sangue , Aborto Habitual/etiologia , Adulto , Feminino , Humanos , Isoanticorpos/análise , Isoanticorpos/sangue , Gravidez , Tunísia
11.
Int Immunopharmacol ; 76: 105881, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520989

RESUMO

The association between immunosuppressive therapy or cytomegalovirus (CMV) infection and detection of de novo donor-specific antibody (dnDSA) at 1 year after transplantation was evaluated. The impact of dnDSA positivity at 1 year after transplantation on long-term death-censored renal graft survival was also evaluated. One hundred and sixty adults receiving living renal allografts were studied. Inclusion criteria were renal graft survival for at least 1 year and a standard regimen of immunosuppressive therapy with tacrolimus, mycophenolate mofetil (MMF), steroids, and basiliximab. DSA were measured retrospectively by the Luminex assay. The coefficient of variation (CV) was calculated and receiver operating characteristic (ROC) analysis was employed to clarify the association of tacrolimus with development of dnDSA. Seven of the 160 patients (4.4%) were positive for dnDSA. The intra-patient minimum trough level of tacrolimus (cutoff value: 3.2 ng/mL) was associated with development of dnDSA. Discontinuation of MMF and treatment of CMV infection were more frequent in patients with dnDSA than in those without dnDSA. In multivariate analysis, a low trough level of tacrolimus, discontinuation of MMF, and treatment of CMV infection within 1 year after transplantation were independently associated with detection of dnDSA at 1 year. In patients with or without dnDSA at 1 year, the 10-year allograft survival rate was 51.4 versus 87.9%, respectively (P = 0.002). A lower tacrolimus trough level, discontinuation of MMF, and treatment of CMV infection were associated with dnDSA positivity. Further investigation is needed to determine whether a new immunosuppressive regimen that avoids these factors can reduce dnDSA positivity.


Assuntos
Infecções por Citomegalovirus/imunologia , Imunossupressores/administração & dosagem , Isoanticorpos/sangue , Transplante de Rim , Adulto , Idoso , Basiliximab/administração & dosagem , Citocromo P-450 CYP3A/genética , Infecções por Citomegalovirus/genética , Feminino , Humanos , Imunossupressores/farmacocinética , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/farmacocinética , Polimorfismo Genético , Tacrolimo/administração & dosagem , Tacrolimo/farmacocinética , Adulto Jovem
12.
Transfus Med ; 29(5): 344-350, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31502333

RESUMO

OBJECTIVES: To provide a novel assay to detect incomplete antibodies in the crossmatching test. BACKGROUND: There is a requirement in China that both major and minor crossmatch tests are required. Among all methods of crossmatching, the tube anti-human globulin test requires tedious washing steps and is time-consuming, whereas the microcolumn gel immunoassay anti-human globulin test is susceptible to sample quality. METHODS: The process of the microplate hydrogel immunoassay anti-human globulin test involves the use of our patented hydrogel chromatography medium and U-bottom microplates pre-coated with goat anti-human globulin (AHG). A mixture of red blood cells (RBCs) and serum is centrifuged through the hydrogel under precise conditions. In incompatible reactions, the sensitised RBCs are captured by the pre-coated AHG and form a layer over the bottom of the well, whereas in compatible reactions, the unbound RBCs form a button at the bottom of the well. The sensitivity of this new approach and the performance when testing old specimens were evaluated. RESULTS: This approach was more convenient and slightly more sensitive than the tube anti-human globulin test and was superior to the microcolumn gel immunoassay when testing old specimens. CONCLUSION: In general, this assay is suitable for the routine clinical use of crossmatching to detect incomplete antibodies.


Assuntos
Tipagem e Reações Cruzadas Sanguíneas/métodos , Hidrogéis/química , Isoanticorpos/sangue , Tipagem e Reações Cruzadas Sanguíneas/instrumentação , Humanos , Imunoensaio , Sensibilidade e Especificidade
13.
Fetal Diagn Ther ; 46(6): 433-439, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31434085

RESUMO

Only few studies have reported on Jra alloimmunization in pregnancy, and its clinical course remains unclear. We reviewed our cases to clarify the change in the peak systolic velocity of the middle cerebral artery (MCA-PSV) during pregnancy and the critical anti-Jra antibody titer to predict fetal anemia. We collected the data of pregnant women with anti-Jra antibody from two hospitals between 2010 and 2017. We extracted data on maternal information, number of intrauterine blood transfusions (IUT), trend of anti-Jra antibody titer, changes of MCA-PSV, and neonatal outcome. We had 16 cases. IUTs were performed in 6 fetuses with severe anemia between 27 and 32 weeks' gestation. The MCA-PSV did not increase more than 1.5 multiples of the median (MoM) after 32 weeks' gestation. No significant difference was found in the maximum titer between cases with IUT and those without IUT. All pregnancies but one delivered at term. No neonates developed severe anemia or jaundice. MCA-PSV did not increase higher than 1.5 MoM later during the pregnancy. A critical titer to predict fetal anemia did not exist. Spontaneous term delivery could be expected even in fetuses who underwent IUT before 32 weeks' gestation.


Assuntos
Anemia/imunologia , Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Eritrócitos/imunologia , Doenças Fetais/imunologia , Isoanticorpos/sangue , Anemia/sangue , Anemia/terapia , Velocidade do Fluxo Sanguíneo , Incompatibilidade de Grupos Sanguíneos/sangue , Incompatibilidade de Grupos Sanguíneos/terapia , Transfusão de Sangue Intrauterina/efeitos adversos , Circulação Cerebrovascular , Feminino , Doenças Fetais/sangue , Doenças Fetais/terapia , Idade Gestacional , Humanos , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Gravidez , Estudos Retrospectivos , Resultado do Tratamento
14.
Stem Cell Reports ; 13(2): 254-261, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31378671

RESUMO

Four boys with Pelizaeus-Merzbacher disease, an X-linked leukodystrophy, underwent transplantation with human allogeneic central nervous system stem cells (HuCNS-SC). Subsequently, all subjects were followed for an additional 4 years in this separate follow-up study to evaluate safety, neurologic function, magnetic resonance imaging (MRI) data, and immunologic response. The neurosurgical procedure, immunosuppression, and HuCNS-SC transplantation were well tolerated and all four subjects were alive at the conclusion of the study period. At year 2, all subjects exhibited diffusion MRI changes at the implantation sites as well as in more distant brain regions. There were persistent, increased signal changes in the three patients who were studied up to year 5. Two of four subjects developed donor-specific HLA alloantibodies, demonstrating that neural stem cells can elicit an immune response when injected into the CNS, and suggesting the importance of monitoring immunologic parameters and identifying markers of engraftment in future studies.


Assuntos
Encéfalo/diagnóstico por imagem , Células-Tronco Neurais/transplante , Doença de Pelizaeus-Merzbacher/terapia , Encéfalo/fisiologia , Pré-Escolar , Seguimentos , Antígenos HLA/imunologia , Humanos , Lactente , Isoanticorpos/sangue , Imagem por Ressonância Magnética , Masculino , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Doença de Pelizaeus-Merzbacher/imunologia , Doença de Pelizaeus-Merzbacher/patologia , Índice de Gravidade de Doença , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo , Resultado do Tratamento
15.
BMC Anesthesiol ; 19(1): 130, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315561

RESUMO

BACKGROUND: Risk of over-immunosuppression or immunization may mitigate the overall and long-term renal outcomes of kidney transplant recipients (KTR) admitted to the ICU in the modern era but remain poorly described. Thus, there is an unmet need to better characterize the survival of KTR admitted to the ICU, but also the renal and immunological outcomes of survivors. METHODS: Retrospective observational study that included 200 KTR admitted between 2010 and 2016 to the ICU of a teaching hospital (median age 61 years [IQR 50.7-68]; time from transplantation 41 months [IQR 5-119]). Survival curves were compared using the Log-rank test. RESULTS: Mortality rates following admission to the ICU was low (26.5% at month-6), mainly related to early mortality (20% in-hospital), and predicted by the severity of the acute condition (SAPS2 score) but also by Epstein Barr Virus proliferation in the weeks preceding the admission to the ICU. Acute kidney injury (AKI) was highly prevalent (85.1%). Progression toward chronic kidney disease (CKD) was observed in 45.1% of survivors. 15.1% of survivors developed new anti-HLA antibodies (donor-specific antibodies 9.2% of cases) that may impact the long-term renal transplantation function. CONCLUSIONS: Notwithstanding the potential biases related to the retrospective and monocentric nature of this study, our findings obtained in a large cohort of KTR suggest that survival of KTR admitted in ICU is good but in-ICU management of these patients may alter both survival and AKI to CKD transition, as well as HLA immunization. Further interventional studies, including systematic characterization of the Epstein Barr virus proliferation at the admission (i.e., a potential surrogate marker of an underlying immune paralysis and frailty) will need to address the optimal management of immunosuppressive regimen in ICU to improve survival but also renal and immunological outcomes.


Assuntos
Mortalidade Hospitalar , Unidades de Terapia Intensiva , Transplante de Rim , Transplantados , Lesão Renal Aguda/epidemiologia , Idoso , Citomegalovirus/fisiologia , Progressão da Doença , Feminino , França/epidemiologia , Antígenos HLA/imunologia , Herpesvirus Humano 4/fisiologia , Humanos , Imunossupressores/uso terapêutico , Infecções/epidemiologia , Isoanticorpos/sangue , Masculino , Necrose Hepática Massiva/mortalidade , Pessoa de Meia-Idade , Neoplasias/mortalidade , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Choque Cardiogênico/mortalidade , Acidente Vascular Cerebral/mortalidade , Viremia/mortalidade , Replicação Viral
16.
Transplant Proc ; 51(7): 2302-2307, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31358448

RESUMO

PURPOSE: HLA antibodies have been shown to be associated with late graft loss. In this study, we defined the incidence and profiles of anti-HLA antibodies and their impact on graft outcome in long-term kidney recipients. METHODS: The sera of 118 kidney transplant recipients were screened for anti-HLA antibody presence. The antigen specificity of the detected HLA class I and class II antibodies was identified using a Luminex assay (Luminex Corp, Austin, TX, United States). Presence of donor specific antibodies (DSA) was examined in individuals with anti-HLA antibodies using the Luminex method. RESULTS: Anti-HLA class I and/or class II antibodies were detected in serum of 16.1% of the kidney transplant patients. The antibodies were directed against HLA class I antigens in 4 patients (21.1%), HLA class II antigens in 9 patients (47.4%), and both class I and class II antigens in 6 patients (31.6%). The overall prevalence of DSA was 10.2%. Anti-HLA antibodies were significantly associated with higher rate of cyclosporine use. Presence of DSA was associated with a lower rate of tacrolimus use, a higher rate of cyclosporine use, and lower donor age. Presence of anti-HLA antibodies was associated with higher acute cellular rejection and higher chronic active humoral rejection rates. Presence of DSA was associated with chronic active humoral rejection. CONCLUSION: The presence of either HLA antibodies or DSA significantly correlated with lower graft survival, poor transplant function, and proteinuria.


Assuntos
Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Isoanticorpos/sangue , Transplante de Rim/efeitos adversos , Adulto , Especificidade de Anticorpos , Feminino , Sobrevivência de Enxerto/imunologia , Humanos , Imunossupressores/uso terapêutico , Isoanticorpos/imunologia , Rim/imunologia , Transplante de Rim/métodos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Proteinúria/imunologia , Tacrolimo/uso terapêutico , Transplantes/imunologia , Resultado do Tratamento
17.
Blood Transfus ; 17(3): 223-228, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31246563

RESUMO

One of the most serious complications of the treatment of severe haemophilia A is the development of alloantibodies against exogenous factor VIII (FVIII). Inhibitors render factor replacement therapy ineffective, exposing patients to a remarkably high risk of morbidity and mortality. Besides the well-known bypassing agents (i.e. activated prothrombin complex concentrate and recombinant activated factor VII) used to treat or prevent bleeding in haemophilia patients with inhibitors, there is growing interest in newer haemostatic therapies that are not based on the replacement of the deficient FVIII. This review will focus on the most interesting among these innovative therapies, emicizumab, and will provide an update on its current stage of clinical development.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Fator VIII , Fator VIIa/uso terapêutico , Hemofilia A , Isoanticorpos/sangue , Fator VIII/antagonistas & inibidores , Fator VIII/metabolismo , Hemofilia A/sangue , Hemofilia A/tratamento farmacológico , Humanos , Proteínas Recombinantes/uso terapêutico
20.
J Am Soc Nephrol ; 30(7): 1206-1219, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31227636

RESUMO

BACKGROUND: Donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logical target of therapy given their critical role in antibody production. METHODS: To target plasma cells, we treated sensitized rhesus macaques with daratumumab (anti-CD38 mAb). Before transplant, we sensitized eight macaques with two sequential skin grafts from MHC-mismatched donors; four of them were also desensitized with daratumumab and plerixafor (anti-CXCR4). We also treated two patients with daratumumab in the context of transplant. RESULTS: The animals treated with daratumumab had significantly reduced donor-specific antibody levels compared with untreated controls (57.9% versus 13% reduction; P<0.05) and prolonged renal graft survival (28.0 days versus 5.2 days; P<0.01). However, the reduction in donor-specific antibodies was not maintained because all recipients demonstrated rapid rebound of antibodies, with profound T cell-mediated rejection. In the two clinical patients, a combined heart and kidney transplant recipient with refractory antibody-mediated rejection and a highly sensitized heart transplant candidate, we also observed a significant decrease in class 1 and 2 donor-specific antibodies that led to clinical improvement of antibody-mediated rejection and to heart graft access. CONCLUSIONS: Targeting CD38 with daratumumab significantly reduced anti-HLA antibodies and anti-HLA donor-specific antibodies in a nonhuman primate model and in two transplant clinical cases before and after transplant. This supports investigation of daratumumab as a potential therapeutic strategy; however, further research is needed regarding its use for both antibody-mediated rejection and desensitization.


Assuntos
Anticorpos Monoclonais/farmacologia , Transplante de Rim , ADP-Ribosil Ciclase 1/antagonistas & inibidores , ADP-Ribosil Ciclase 1/fisiologia , Adulto , Animais , Citotoxicidade Celular Dependente de Anticorpos , Rejeição de Enxerto , Antígenos HLA/imunologia , Compostos Heterocíclicos/farmacologia , Humanos , Isoanticorpos/sangue , Macaca mulatta , Masculino , Linfócitos T Reguladores/efeitos dos fármacos
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