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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.
Einstein (Sao Paulo) ; 18: eRC4582, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31531557

RESUMO

The correct identification of erythrocyte antibodies is fundamental for the searching for compatible blood and haemolytic transfusion reactions prevention. Antibodies against antigens of high prevalence are difficult to identify because of the rarity of their occurrence and unavailability of negative red cells for confirmation. We report a case of 46-years-old woman, diagnosed with hemoglobinopathy, and who had symptomatic fall in hemoglobin levels (5.3g/dL) after blood transfusion suggestive of transfusion reaction. The patient's blood type was O RhD-positive. Irregular antibody screening was positive and demonstrated a panreaction against all erythrocytes tested, but this result was not reactive with dithiothreitol. Using negative red cells for antigens of high prevalence of our inventory we could identify in the serum of the same erythrocytes an anti-Holley antibody associated with anti-E. Molecular analysis confirmed that the patient was negative for E and Holley antigens. The crossmath with compatible units confirmed the results. Holley is a high prevalence antigen of the Dombrock blood system whose negative phenotype is extremely rare in all populations and is associated with hemolytic transfusion reactions. This is an antibody that is difficult to identify because laboratories need to have experience in solving complex cases, and have available a large stock of rare sera and erythrocytes, as well other tools such as enzymes, thiol reagents and molecular tests. The correct identification of a rare antibody is initial and mandatory for searching of compatible donors, and to guarantee a satisfactory transfusional support.


Assuntos
Anticorpos/imunologia , Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Reação Transfusional/imunologia , Anticorpos/sangue , Eritrócitos/imunologia , Feminino , Testes Hematológicos/métodos , Humanos , Imunoglobulinas/sangue , Isoanticorpos/imunologia , Pessoa de Meia-Idade
3.
Trials ; 20(1): 476, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383029

RESUMO

BACKGROUND: Chronic rejection is the single biggest cause of premature kidney graft failure. HLA antibodies (Ab) are an established prognostic biomarker for premature graft failure so there is a need to test whether treatment decisions based on the presence of the biomarker can alter prognosis. The Optimised TacrolimuS and MMF for HLA Antibodies after Renal Transplantation (OuTSMART) trial combines two elements. Firstly, testing whether a routine screening programme for HLA Ab in all kidney transplant recipients is useful by comparing blinding versus unblinding of HLA Ab status. Secondly, for those found to be HLA Ab+, testing whether the introduction of a standard optimisation treatment protocol can reduce graft failure rates. METHODS: OuTSMART is a prospective, open-labelled, randomised biomarker-based strategy (hybrid) trial, with two arms stratified by biomarker (HLA Ab) status. The primary outcome was amended from graft failure rates at 3 years to time to graft failure to increase power and require fewer participants to be recruited. Length of follow-up subsequently is variable, with all participants followed up for at least 43 months up to a maximum of 89 months. The primary outcome will be analysed using Cox regression adjusting for stratification factors. Analyses will be according to the intention-to-treat using all participants as randomised. Outcomes will be analysed comparing standard care versus biomarker-led care groups within the HLA Ab+ participants (including those who become HLA Ab+ through re-screening) as well as between HLA-Ab-unblinded and HLA-Ab-blinded groups using all participants. DISCUSSION: Changes to the primary outcome permit recruitment of fewer participants to achieve the same statistical power. Pre-stating the statistical analysis plan guards against changes to the analysis methods at the point of analysis that might otherwise introduce bias through knowledge of the data. Any deviations from the analysis plan will be justified in the final report. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN46157828 . Registered on 26 March 2013; EudraCT 2012-004308-36 . Registered on 10 December 2012.


Assuntos
Interpretação Estatística de Dados , Rejeição de Enxerto/complicações , Antígenos HLA/imunologia , Isoanticorpos/imunologia , Transplante de Rim/efeitos adversos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Doença Crônica , Humanos , Estudos Prospectivos , Projetos de Pesquisa , Tamanho da Amostra
4.
Ann Transplant ; 24: 454-460, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31383839

RESUMO

BACKGROUND The appearance of human leukocyte antigen (HLA) antibodies after solid organ transplantation predisposes recipients to graft dysfunction. In theory, vascular homografts, which are widely used in children with congenital heart defects, may cause allosensitization. MATERIAL AND METHODS In this single-center retrospective study, the presence of pre-existing HLA antibodies in pediatric heart transplant (HTx) recipients with a vascular homograft was evaluated in a cohort of 12 patients. HLA antibodies were screened before and after HTx and positive screening results were confirmed and identified using the Luminex® single antigen bead method. Endomyocardial biopsies (EMB) and coronary angiography studies were re-evaluated to assess the prevalence of acute rejections and coronary artery change in these patients. RESULTS At the time of HTx, 8 patients (67%) had HLA antibodies detected by the Luminex assay, none of which were heart donor specific (DSA). All patients had negative leukocyte crossmatch. One patient developed DSAs against homograft donor prior to HTx. After the HTx, 5 patients (42%) developed DSAs against the heart donor and 4 patients (40%) against the homograft donor. In 2 patients (17%), the antibodies were against both heart and homograft donors. The rejection rate or prevalence of coronary artery vasculopathy did not differ significantly between the homograft cohort and our historical controls. CONCLUSIONS Our results suggest that the prevalence of DSAs against homograft donor prior to HTx is relatively rare. However, almost half of the patients developed DSAs against homograft post-HTx. The clinical importance of these antibodies warrants further studies.


Assuntos
Antígenos HLA/imunologia , Transplante de Coração/efeitos adversos , Isoanticorpos/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Lactente , Masculino , Estudos Retrospectivos
6.
J Vet Intern Med ; 33(5): 2037-2045, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31361062

RESUMO

BACKGROUND: Acute hemolytic transfusion reactions because of dog erythrocyte antigen (DEA) 1 sensitization after mismatched transfusions are serious complications. Dog erythrocyte antigen 1 expression varies from negative to weakly to strongly positive. OBJECTIVES: To assess alloimmunization after transfusion of weakly DEA 1+ blood to a DEA 1- dog. ANIMALS: One DEA 1- recipient and 1 weakly DEA 1+ donor, and 106 control dogs. METHODS: Long-term follow-up study. Matched for DEA 3, 4, 5, and 7, Dal, and Kai 1 and 2, weakly DEA 1+ donor packed red blood cells (RBCs) were transfused 3 times (0.45 mL/kg at Day 0, 16, and 37) to a DEA 1- recipient. Alloantibodies against RBCs from donor and 106 controls were determined in recipient's plasma samples using a commercial antiglobulin-enhanced immunochromatographic strip and gel tube crossmatches. Alloantibody titers were determined. RESULTS: The DEA 1- recipient was sensitized after 16 days to ≥1657 days after transfusion to weakly DEA 1+ and otherwise matched RBCs. Strong to moderate crossmatch incompatibilities were observed between recipient's plasma and all 61 DEA 1+ crossmatched controls. Moderate to weak incompatibilities were also observed to DEA 1- controls. Anti-DEA 1 and other alloantibodies were detected over the 4.5 year observation period. CONCLUSIONS AND CLINICAL IMPORTANCE: Blood from a weakly DEA 1+ donor induces a strong and durable alloimmunization in a DEA 1- recipient dog. Additional alloantibodies developed against yet to be defined RBC antigens. Those results support the recommendation of typing dogs against DEA 1, considering weakly DEA 1+ as immunogenic, and crossmatching all previously transfused dogs.


Assuntos
Antígenos de Grupos Sanguíneos/imunologia , Tipagem e Reações Cruzadas Sanguíneas/veterinária , Transfusão de Sangue/veterinária , Cães/imunologia , Animais , Incompatibilidade de Grupos Sanguíneos/veterinária , Cães/sangue , Eritrócitos/imunologia , Isoanticorpos/imunologia
8.
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
9.
Int J Immunogenet ; 46(5): 307-320, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31183978

RESUMO

The detection and semiquantitative measurement of circulating human leucocyte antigen (HLA)-specific antibodies is essential for the management of patients before and after transplantation. In addition, the pretransplant cross-match to assess the reactivity of recipient HLA antibody against donor lymphocytes has long been the gold standard to prevent hyperacute rejection. Whilst both of these tests assume that recipient HLA-specific antibody is the only variable in the assessment of transplant risk, this is not the case. Transplant immunologists recognize that some HLA antigens are expressed at levels a magnitude lower than others (e.g., HLA-C, HLA-DQ), but within loci, and between different cell types there are many factors that influence HLA expression in both resting and activated cells. HLA is not usually expressed without the specific promoter proteins NLRC5, for HLA class I, and CIITA, for class II. The quantity of HLA protein production is then affected by factors including promoter region polymorphisms, alternative exon splice sites, methylation and microRNA-directed degradation. Different loci are influenced by multiple combinations of these control mechanisms making prediction of HLA regulation difficult, but an ability to measure the cellular expression of each HLA antigen, in conjunction with knowledge of circulating HLA-specific antibody, would lead to a more informed algorithm to assess transplant risk.


Assuntos
Regulação da Expressão Gênica , Antígenos HLA/genética , Antígenos HLA/imunologia , Membrana Celular/imunologia , Membrana Celular/metabolismo , Epigênese Genética , Variação Genética , Humanos , Isoanticorpos/imunologia , Polimorfismo Genético , Regiões Promotoras Genéticas , Processamento Pós-Transcricional do RNA , Imunologia de Transplantes
10.
Immunobiology ; 224(4): 485-489, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31204065

RESUMO

Parathyroid allotransplantation is increasingly practiced for patients who have permanent hypoparathyroidsm. Parathyroid allotransplantation success is varied, and no defined criteria about immunologic monitoring for pre-/post-transplantation follow-up. This study sought to evaluate the possible role of immunological tests. Four unrelated recipients and one living donor who have chronic kidney disease were evaluated for HLA-typing, PRA, CXM tests to conduct parathyroid allotransplantation. Parathyroid glands were obtained and resected from the donor, then cells were isolated and cryopreserved. Upon histologic examination, cells were cultivated and injected into muscle of four recipients. Recipient's were followed for parathormone and calcium levels for four years. PRA screening were monitored and de novo DSA was evaluated as well. In two of the recipients, allografts continued to be functional more than four years. In one recipient, allograft remained functional for two years and another recipient lost function after one year. Two out four were negative for de novo DSA and three out of four of the recipients remained negative for PRA. Neither HLA-matching nor de novo DSA positivity and PRA screenings seems significant for successfull parathyroid allotransplantation. This study has considerable potential for immunological monitoring of parathyroid allotransplantation.


Assuntos
Antígenos HLA/imunologia , Teste de Histocompatibilidade , Isoanticorpos/imunologia , Glândulas Paratireoides/imunologia , Glândulas Paratireoides/transplante , Doadores de Tecidos , Adulto , Alelos , Biomarcadores , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/genética , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/metabolismo , Imunologia de Transplantes , Transplante Homólogo
11.
Biomed Res Int ; 2019: 6387924, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223621

RESUMO

Follicular helper T cells (Tfh cells) are closely related to the occurrence and development of antibody-mediated rejection (AMR) after renal transplantation. Exosomes play a key role in the rejection after organ transplantation. However, whether Tfh-derived exosomes are involved in AMR has not been reported. We collected peripheral blood from 42 kidney transplant patients and found no significant differences in CD4+CXCR5+ and CD4+CXCR5+CXCR3+CCR6-exosomes between AMR and non-AMR groups, whereas the proportion of CD4+CXCR5+CXCR3-exosomes was significantly higher in AMR group than that in non-AMR group; CTLA-4 expression of CD4+CXCR5+exosomes was significantly lower in AMR group than that in non-AMR group. HLA-G expression was not significantly different between two groups. We further separated CD4+CXCR5+cells from patients by magnetic beads. Coculture experiments showed that Tfh cell-derived exosomes in AMR patients significantly promoted B cell proliferation and differentiation, compared with non-AMR group, the percentage of B cells and plasma cells increased by 87.52% and 110.2%, respectively. In conclusion, our study found that Tfh cell-derived exosomes could promote the proliferation and differentiation of B cells and they may play an important role in the development of AMR after renal transplantation.


Assuntos
Exossomos/imunologia , Rejeição de Enxerto/imunologia , Isoanticorpos/imunologia , Transplante de Rim , Plasmócitos/imunologia , Adulto , Proliferação de Células , Exossomos/patologia , Feminino , Regulação da Expressão Gênica/imunologia , Rejeição de Enxerto/patologia , Antígenos HLA-G/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Plasmócitos/patologia , Linfócitos T Auxiliares-Indutores/patologia
12.
J Immunol Res ; 2019: 2754920, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223627

RESUMO

Transferon® is an immunomodulator made of a complex mixture of peptides from human dialyzable leucocyte extracts (hDLEs). Development of surrogate antibodies directed to hDLE is an indispensable tool for studies during process control and preclinical trials. These antibodies are fundamental for different analytical approaches, such as identity test and drug quantitation, as well as to characterize its pharmacokinetic and mechanisms of action. A previous murine study showed the inability of the peptides of Transferon® to induce antibody production by themselves; therefore, in this work, two approaches were tested to increase its immunogenicity: chemical conjugation of the peptides of Transferon® to carrier proteins and the use of a rabbit model. Bioconjugates were generated with Keyhole Limpet Hemocyanin (KLH) or Bovine Serum Albumin (BSA) through maleimide-activated carrier proteins. BALB/c mice and New Zealand rabbits were immunized with Transferon® conjugated to KLH or nonconjugated Transferon®. Animals that were immunized with conjugated Transferon® showed significant production of antibodies as evinced by the recognition of Transferon®-BSA conjugate in ELISA assays. Moreover, rabbits showed higher antibody titers when compared with mice. Neither mouse nor rabbits developed antibodies when immunized with nonconjugated Transferon®. Interestingly, rabbit antibodies were able to partially block IL-2 production in Jurkat cells after costimulation with Transferon®. In conclusion, it is feasible to elicit specific and functional antibodies anti-hDLE with different potential uses during the life cycle of the product.


Assuntos
Isoanticorpos/imunologia , Fator de Transferência/efeitos adversos , Adjuvantes Imunológicos , Animais , Formação de Anticorpos , Especificidade de Anticorpos/imunologia , Antígenos/administração & dosagem , Antígenos/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imunização , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Isoanticorpos/isolamento & purificação , Masculino , Camundongos , Peptídeos/administração & dosagem , Peptídeos/imunologia , Coelhos , Fator de Transferência/imunologia , Fator de Transferência/uso terapêutico
15.
Biomed Pharmacother ; 116: 109020, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152928

RESUMO

Glomerulonephritis is the major cause of chronic kidney disease characterized by mesangial cell proliferation and extracellular matrix deposition. The aim of this study was to investigate the effects of Lycium barbarum polysaccharides (LBPs) on anti-Thy 1 nephritis rats and explore the protective mechanism of LBPs. After the model of glomerulonephritis created by injecting anti-thymocyte serum (ATS), rats were treated with enalapril or LBPs for 8 weeks. The therapeutic effect was evaluated by detection of renal-related biochemical parameters, histological observation and markers of renal fibrosis. Moreover, RNA-seq analysis and experiments in vitro were employed to explore the signaling pathway involved in LBPs treatment. The results found that LBPs treatment significantly suppressed ATS-caused increment at levels of blood urea nitrogen, creatinine, proteinuria, PAI-1 protein expression, glomerular mesangial cell proliferation and extracellular matrix hyperplasia, along with reduction of creatinine clearance. RNA sequencing showed pyruvate metabolism acting as a potential signaling pathway, which was evidenced by the inhibitory effect on up-regulation of pyruvate dehydrogenase and PAI-1 levels via treatment with LBPs in vitro. LBPs are the promising agents for the management of glomerulonephritis through pyruvate metabolism signaling pathway.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/enzimologia , Isoanticorpos/imunologia , Complexo Piruvato Desidrogenase/metabolismo , Animais , Medicamentos de Ervas Chinesas/farmacologia , Fibrose , Glomerulonefrite/genética , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Rim/ultraestrutura , Testes de Função Renal , Masculino , Camundongos , Piruvatos/metabolismo , Ratos Sprague-Dawley , Coloração e Rotulagem
16.
Int Rev Immunol ; 38(3): 106-117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31233364

RESUMO

A growing body of evidence shows that donor-specific antibodies (DSA) are associated with rejection and allograft failure following both liver and intestinal transplantation. However, data have clearly shown that not all DSA are injurious. The reasons for this remain unclear but appear to be multifactorial, impacted by clinical factors such as immunosuppression and infection as well as immunologic factors such as HLA expression and donor-specific antibodies affinity. Establishing a diagnosis of antibody-mediated rejection (AMR) remains clinically challenging, especially given that AMR can present as either acute or chronic graft dysfunction. These observations highlight the need for a better understanding of the immune mechanisms by which DSA and AMR contribute to rejection and allograft failure. This review focuses on current knowledge of DSA and AMR in liver and intestinal transplant recipients and specifically highlights the clinical impact, prevalence, and pathogenesis.


Assuntos
Intestinos/transplante , Isoanticorpos/imunologia , Transplante de Fígado/efeitos adversos , Doadores de Tecidos , Doença Aguda , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Doença Crônica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/terapia , Antígenos HLA/imunologia , Humanos , Transplante de Fígado/métodos , Prevalência , Fatores de Risco , Transplante Homólogo
17.
Int Immunopharmacol ; 73: 491-501, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173971

RESUMO

Hydrogen sulfide (H2S) has emerged as an important biological mediator with numerous pathophysiological roles. One of the well-documented actions of H2S is to inhibit immunity, especially cellular immunity. Currently, limited information is available regarding its effects on humoral immunity. Given that H2S has reducing activity and that the effector molecules in humoral immunity, such as antibody and complement, contain abundant disulfide bonds that are indispensable for their functions, we speculated that H2S might regulate antibody activity via modification of disulfide bonds. Here we addressed this possibility. Exposure of antibodies to H2S donors resulted in cleavage of the disulfide bonds between the heavy and light chains of antibodies, which was associated with antibody sulfhydration. Further analysis revealed that H2S-treated antibodies exhibited a marked reduction in antigen binding ability. It potently prevented the antibody-mediated agglutination of red blood cells and interrupted aggregation of antibody-coated microspheres. H2S also greatly inhibited antibody-induced and complement-mediated cell lysis in glomerular mesangial cells, as well as anti-CD95 IgM antibody-initiated cell apoptosis in Jurkat cells. Moreover, it significantly suppressed the alternative complement activation pathway. Collectively, our results revealed, for the first time, that pharmacologic levels of H2S inhibit humoral immune responses via direct sulfhydration of the effector molecules. Our study thus provides novel mechanistic insights into the immunoregulatory actions of H2S and suggests that H2S may have potential to treat certain humoral immune diseases.


Assuntos
Sulfeto de Hidrogênio/imunologia , Sulfetos/farmacologia , Animais , Anticorpos Monoclonais/imunologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Proteínas do Sistema Complemento/imunologia , Eritrócitos/efeitos dos fármacos , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Isoanticorpos/imunologia , Células Mesangiais/efeitos dos fármacos , Camundongos , Coelhos , Ratos , Linfócitos T/efeitos dos fármacos
18.
Blood Transfus ; 17(4): 307-311, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31184578

RESUMO

BACKGROUND: Antibody-mediated haemolysis due to passenger lymphocyte syndrome arising in the setting of solid organ transplant can be devastating. Some degree of passenger lymphocyte syndrome is said to occur in up to 10% of ABO mismatched renal transplants, 40% of ABO mismatched liver transplants, and 70% of ABO mismatched heart-lung transplants; a reflection of the number of memory B cells transplanted with the organ. Passenger lymphocyte syndrome is less common with minor red cell antigens but can still be severe. MATERIALS AND METHODS: We review a series of patients who developed passenger lymphocyte syndrome after solid organ transplantation. Conventional serological testing was performed using tube and solid-phase testing. Molecular testing was performed using a gene-chip array. RESULTS: In patients receiving a minor antigen mismatched organ transplant and multiple allogenic red cell transfusions, serological methods proved insufficient to resolve the source of minor blood group antibodies that arose in the aftermath of the transplant. Genetic testing was able to clearly resolve donor and recipient types. DISCUSSION: Passenger lymphocyte syndrome after mismatched organ transplantation is not rare, but the syndrome associated with non-ABO antibodies occurs in a much smaller subset of these cases. The mixtures of organ donor, recipient, and other transfused red blood cells profoundly limit the usefulness of serological testing. Genetic assignment of minor blood types to donor and recipient can guide therapy and inform prognosis.


Assuntos
Incompatibilidade de Grupos Sanguíneos/genética , Transfusão de Eritrócitos/efeitos adversos , Hemólise , Isoanticorpos/genética , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Sistema do Grupo Sanguíneo ABO/genética , Sistema do Grupo Sanguíneo ABO/imunologia , Adulto , Idoso , Incompatibilidade de Grupos Sanguíneos/imunologia , Testes Genéticos , Transplante de Coração/efeitos adversos , Humanos , Isoanticorpos/imunologia , Linfócitos/imunologia , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos
19.
Hum Immunol ; 80(7): 478-486, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31080010

RESUMO

Accurate identification of HLA antibodies using the single antigen bead (SAB) assay is critical for assessment of pre/post-transplant immunological risk and successful virtual crossmatching. Unfortunately, high titer HLA antibodies can be missed or underestimated in the SAB assay as a result of interference with the detection of IgG. This so called prozone effect has been attributed to both complement- and IgM-dependent mechanisms and can be minimized with serum dilution or treatment with heat, EDTA, or DTT. In this study we describe the frequency, nature, and degree of prozone in a cohort of highly sensitized patients (cPRA ≥ 95%), in whom accurate detection of HLA antibodies and virtual crossmatching is of paramount importance. Sera were tested by the SAB assay ±â€¯EDTA treatment, ±1:10 dilution to identify the prozone effect. The relative contribution of complement vs IgM to prozone was assessed using anti-C3d and anti-IgM reporter antibodies, respectively. We found that prozone was very frequent in highly sensitized patients (80%), especially those with a history of previous transplantation (87%). Class I HLA specificities were more commonly affected than class II and the susceptibility to prozone was locus dependent with HLA-A(31%), -B(29%) and -DQ(26%) being affected more frequently than HLA-DP(17%), -C(16%) and -DR(5%) antigens. Interestingly, the presence of prozone could be predicted by C3d positivity (MFI ≥ 4000; sensitivity = 95.2%, specificity = 97.2%) and the degree of prozone correlated directly with the extent of C3d deposition. The role of IgM was less clear. However, serum dilution studies suggested that IgM may contribute to interference in a small subset of prozone positive specificities. Our study underscores the importance of serum treatment to inhibit complement activation and minimize prozone in the SAB assay, especially in highly sensitized patients.


Assuntos
Antígenos HLA/imunologia , Teste de Histocompatibilidade , Isoanticorpos/imunologia , Estudos de Coortes , Ativação do Complemento , Complemento C3d/imunologia , Ácido Edético/farmacologia , Feminino , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Transplante de Rim , Masculino , Ficoeritrina/imunologia , Gravidez , Soro/efeitos dos fármacos , Listas de Espera
20.
Transplant Proc ; 51(4): 1021-1023, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31101163

RESUMO

Cytotoxic flow cytometric crossmatch (cFCXM), identified by detecting complement-mediated cytotoxic cell death in addition to the capability of showing the alloantibodies binding onto lymphocytes at the same time, can reduce the necessary time and workload in evaluating alloantibodies. More data from clinical samples are needed for cFCXM to be accepted by tissue typing laboratories. In this study, we compared cFCXM with complement-dependent lymphocytotoxicity and standard flow cytometric crossmatch in 41 renal pretransplant patients. A comparison of the obtained data was performed using Spearman's correlation test. We found that cFCXM showed no statistically significant differences with complement-dependent lymphocytotoxicity and flow cytometric crossmatch. We believe that cFCXM can be used in clinical laboratories in the near future following intra-laboratory validation.


Assuntos
Testes Imunológicos de Citotoxicidade/métodos , Citometria de Fluxo/métodos , Teste de Histocompatibilidade/métodos , Transplante de Rim , Feminino , Humanos , Isoanticorpos/análise , Isoanticorpos/imunologia , Masculino
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