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[PMID]:29460640
[Au] Autor:Sullivan A; Watkinson J; Waddington J; Park BK; Naisbitt DJ
[Ad] Endereço:a MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology , The University of Liverpool , Liverpool , England.
[Ti] Título:Implications of HLA-allele associations for the study of type IV drug hypersensitivity reactions.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):261-274, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Type IV drug hypersensitivity remains an important clinical problem and an obstacle to the development of new drugs. Several forms of drug hypersensitivity are associated with expression of specific HLA alleles. Furthermore, drug-specific T-lymphocytes have been isolated from patients with reactions. Despite this, controversy remains as to how drugs interact with immune receptors to stimulate a T-cell response. Areas covered: This article reviews the pathways of T-cell activation by drugs and how the ever increasing number of associations between expression of HLA alleles and susceptibility to hypersensitivity is impacting on our research effort to understanding this form of iatrogenic disease. Expert opinion: For a drug to activate a T-cell, a complex is formed between HLA molecules, an HLA binding peptide, the drug and the T-cell receptor. T-cell responses can involve drugs and stable or reactive metabolites bound covalently or non-covalently to any component of this complex. Recent research has linked the HLA associations to the disease through the characterization of drug-specific T-cell responses restricted to specific alleles. However, there is now a need to identify the additional genetic or environment factors that determine susceptibility and use our increased knowledge to develop predictive immunogenicity tests that offer benefit to Pharma developing new drugs.
[Mh] Termos MeSH primário: Hipersensibilidade a Drogas/imunologia
Antígenos HLA/imunologia
Hipersensibilidade Tardia/induzido quimicamente
[Mh] Termos MeSH secundário: Alelos
Hipersensibilidade a Drogas/genética
Predisposição Genética para Doença
Seres Humanos
Hipersensibilidade Tardia/genética
Hipersensibilidade Tardia/imunologia
Ativação Linfocitária/efeitos dos fármacos
Ativação Linfocitária/imunologia
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (HLA Antigens)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1441285


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[PMID]:29381772
[Au] Autor:Chen D; Zhou D; Guo D; Xu P; Chen B
[Ad] Endereço:Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People's Republic of China.
[Ti] Título:Comparison of outcomes in hematological malignancies treated with haploidentical or HLA-identical sibling hematopoietic stem cell transplantation following myeloablative conditioning: A meta-analysis.
[So] Source:PLoS One;13(1):e0191955, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Haploidentical and human leukocyte antigen (HLA)-identical sibling hematopoietic stem transplantation are two main ways used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, remarkable progress has been made in haploidentical allo-HSCT (HID-SCT), and some institutions found HID-SCT had similar outcomes as HLA-identical sibling allo-HSCT (ISD-SCT). To clarify if HID-SCT has equal effects to ISD-SCT in hematologic malignancies, we performed this meta-analysis. METHODS: Relevant articles published prior to February 2017 were searched on PubMed. Two reviewers assessed the quality of the included studies and extracted data independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated for statistical analysis. RESULTS: Seven studies including 1919 patients were included. The rate of platelet engraftment is significantly lower after HID-SCT versus ISD-SCT while there is no difference in neutrophil engraftment (OR = 2.58, 95% CI = 1.70-3.93, P < 0.00001). The risk of acute graft-versus-host disease (GVHD) is significantly higher after HID-SCT versus ISD-SCT (OR = 1.88, 95% CI = 1.42-2.49, P < 0.00001), but the relapse rate is lower in HID-SCT group (OR = 0.70, 95% CI = 0.55-0.90, P = 0.005). The incidence rates of overall survival (OS) and disease-free-survival/leukemia-free survival/relapse-free survival (DFS/LFS/RFS) after ISD-SCT are all significantly superior to HID-SCT (OR = 1.32, 95% CI = 1.08-1.62, P = 0.006; OR = 1.25, 95% CI = 1.03-1.52, P = 0.02). There is no significant difference in transplantation related mortality (TRM) rate after HID-SCT and ISD-SCT. CONCLUSION: After myeloablative conditioning, patients receiving ISD-SCT have a faster engraftment, lower acute GVHD and longer life expectancy compared to HID-SCT with GVHD prophylaxis (cyclosporine A, methotrexate, mycophenolate mofetil and antithymoglobulin; CsA + MTX + MMF + ATG). Currently, HID-SCT with GVHD prophylaxis (CsA + MTX + MMF + ATG) may not replace ISD-SCT when HLA-identical sibling donor available.
[Mh] Termos MeSH primário: Doenças Hematológicas/terapia
Condicionamento Pré-Transplante
[Mh] Termos MeSH secundário: Antígenos HLA/imunologia
Haplótipos
Transplante de Células-Tronco Hematopoéticas
Seres Humanos
Análise de Sobrevida
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (HLA Antigens)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191955


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[PMID]:28457920
[Au] Autor:Kauke T; Link M; Rentsch M; Stangl M; Guba M; Andrassy J; Werner J; Meiser B; Fischereder M; Habicht A
[Ad] Endereço:Laboratory of Immunogenetics, University Hospital Munich, Germany; Clinic for General, Visceral-, Transplantation-, Vascular- and Thoracic Surgery, University Hospital Munich, Germany.
[Ti] Título:Antibody response to HBV vaccination on dialysis does not correlate with the development of deNovo anti-HLA antibodies after renal transplantation.
[So] Source:Transpl Immunol;42:5-8, 2017 06.
[Is] ISSN:1878-5492
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Response to Hepatitis B virus (HBV) vaccination can be diminished in some (50-80%) but not all dialysis patients. We hypothesized, that the response to vaccination on dialysis may correlate with the development of anti-HLA antibodies after renal transplantation and might therefore be a valuable parameter to predict alloresponses. METHODS: The response to HBV vaccination on dialysis and the development of deNovo anti-HLA antibodies post-transplant was analyzed in 188 non-immunized renal transplant recipients. The response to HBV vaccination was evaluated by measuring the anti-HBs titer at time of transplantation. Anti-HLA antibodies post-transplant were monitored by serial measurements by means of Luminex. Acute rejection episodes, graft loss and renal dysfunction were assessed within a median follow-up of 5.5years. RESULTS: One hundred and forty-one patients (75%) exhibited an adequate immune response to HBV vaccination on dialysis. Vaccine responder (R) and none responder (NR) did not differ with respect to age, gender and BMI, while R spend significantly more time on dialysis before transplantation (4.58±3.35 vs 3.23±2.55 years, p=0.033). More NR developed deNovo anti-HLA antibodies (27.7 vs 22.7%, p=0.554) and donor-specific anti-HLA antibodies (23.4 vs 14.2%, p=0.173) in comparison to R. Accordingly, the number of acute rejections was higher in NR as compared to R (36.1 vs 24.1%, p=0.130) while graft survival was similar in both groups. CONCLUSION: Contrary to our hypothesis antibody response to HBV vaccination on dialysis does not predict the development of anti-HLA antibodies post transplant.
[Mh] Termos MeSH primário: Formação de Anticorpos
Rejeição de Enxerto/imunologia
Antígenos HLA/imunologia
Vacinas contra Hepatite B/administração & dosagem
Isoanticorpos/imunologia
Transplante de Rim
Diálise Renal
[Mh] Termos MeSH secundário: Adulto
Assistência ao Convalescente
Feminino
Vacinas contra Hepatite B/efeitos adversos
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HLA Antigens); 0 (Hepatitis B Vaccines); 0 (Isoantibodies)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28460445
[Au] Autor:Lv W; Fan Z; Huang F; Xu N; Xuan L; GuopanYu; Jiang Q; Zhou H; Lin R; Zhang X; Sun J; Liu Q
[Ad] Endereço:Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 China.
[Ti] Título:Autoimmune hematological diseases following haploidentical donor hematopoietic stem cell Transplant compared with matched sibling and unrelated donor.
[So] Source:Oncotarget;8(16):26505-26514, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Autoimmune hematological diseases (AHDs) occur more frequently than other autoimmune complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and are often refractory to treatment. This study was to analyze the incidence and risk factors of AHDs as well as their response to treatment . Four hundred and forty-five adult malignant hematopoietic disorders underwent allo-HSCT were enrolled in this retrospective study, including 124 haploidentical donor (HRD), 140 unrelated donor (MUD) and 181 HLA-matched sibling donor (MSD) transplants. Twelve patients developed AHDs, including 6 autoimmune hemolytic anemia and 6 Evans syndrome. Evans syndrome all occurred in HRD transplants. The 3-year cumulative incidence of AHDs was 4.0 ± 1.3%, and HRD had higher incidence than MUD (8.7 ± 3.0% vs 1.8 ± 1.2%, P = 0.012) and MSD (8.7 ± 3.0% vs 3.5 ± 2.6%, P = 0.004 ). The steroids combined with Cyclosporine A were acted as the first line treatment, and the response rate was 73%. No patients experienced recurrence at a median follow up of 313 days after stopping treatment. HRD transplants (vs MUD: HR, 5.87; CI, 1.24 to 27.73; p = 0.026 and vs MSD: HR, 7.70; CI, 1.63 to 36.44; P = 0.010) and concurrent chronic graft versus host disease (HR, 3.76; CI, 1.18 to 11.92; P = 0.025) were risk factors for AHDs.
[Mh] Termos MeSH primário: Doenças Autoimunes/terapia
Doenças Hematológicas/terapia
Transplante de Células-Tronco Hematopoéticas
Irmãos
Doadores não Relacionados
[Mh] Termos MeSH secundário: Adolescente
Adulto
Doenças Autoimunes/diagnóstico
Doenças Autoimunes/mortalidade
Feminino
Doença Enxerto-Hospedeiro/diagnóstico
Doença Enxerto-Hospedeiro/etiologia
Antígenos HLA/genética
Antígenos HLA/imunologia
Doenças Hematológicas/diagnóstico
Doenças Hematológicas/mortalidade
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Transplante de Células-Tronco Hematopoéticas/métodos
Teste de Histocompatibilidade
Seres Humanos
Incidência
Masculino
Meia-Idade
Transplante Homólogo
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HLA Antigens)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15710


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[PMID]:29355683
[Au] Autor:Yang C; Wu J; Zhang X; Wen L; Sun J; Cheng Y; Tang X; Liang B; Chen G; Zhou F; Cui Y; Zhang A; Zhang X; Zheng X; Yang S; Sun L
[Ad] Endereço:Institute of Dermatology and Department of Dermatology of the First Affiliated Hospital, Anhui Medical University, Hefei 230032, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei 230032, China.
[Ti] Título:Fine-mapping analysis of the MHC region for vitiligo based on a new Han-MHC reference panel.
[So] Source:Gene;648:76-81, 2018 Mar 30.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Vitiligo is an immune-related disease with patchy depigmentation of skin and hair caused by selective destruction of melanocytes. In recent decades, many studies have shown the association between vitiligo and HLA genes; however, the results of Han Chinese are scarce. In this study, we performed a fine-mapping analysis of the MHC region in 2818 Han Chinese subjects through a widely used HLA imputation method with a newly built large-scale Han-MHC reference panel. Three new four-digit HLA alleles (HLA-DQB1 ∗ 02:02, HLA-DQA1 ∗ 02:01 and HLA-DPB1 ∗ 17:01) were identified to be associated with the risk of vitiligo, and four previously reported alleles were confirmed. Further conditional analysis revealed that two important variants, HLA-DQß1 amino acid position 135 (OR = 1.79, P = 1.87 × 10 ) and HLA-B amino acid positions 45-46 (OR = 1.44, P = 5.61 × 10 ), conferred most of the MHC associations. Three-dimension ribbon models showed that the former is located within the ß2 domain of the HLA-DQß1 molecule, and the latter lies in the α1 domain of the HLA-B molecule, while both are involved in specific antigen presenting process. Finally, we summarized all significant signals in the MHC region to clarify their complex relationships, and 8.60% of phenotypic variance could be explained based on all reported variants in Han Chinese so far. Our findings highlight the complex genetic architecture of the MHC region for vitiligo in Han Chinese population and expand our understanding of the roles of HLA coding variants in the etiology of vitiligo.
[Mh] Termos MeSH primário: Predisposição Genética para Doença/genética
Antígenos HLA/genética
Polimorfismo de Nucleotídeo Único
Vitiligo/genética
[Mh] Termos MeSH secundário: Alelos
Grupo com Ancestrais do Continente Asiático/genética
China
Mapeamento Cromossômico/métodos
Frequência do Gene
Predisposição Genética para Doença/etnologia
Haplótipos
Seres Humanos
Desequilíbrio de Ligação
Modelos Logísticos
Fatores de Risco
Vitiligo/etnologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HLA Antigens)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180123
[St] Status:MEDLINE


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[PMID]:29270985
[Au] Autor:Liu J; Bian Z; Wang X; Xu LP; Fu Q; Wang C; Chang YJ; Wang Y; Zhang XH; Jiang Z; Huang XJ
[Ad] Endereço:Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
[Ti] Título:Inverse correlation of Vδ2 T-cell recovery with EBV reactivation after haematopoietic stem cell transplantation.
[So] Source:Br J Haematol;180(2):276-285, 2018 01.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Epstein-Barr virus (EBV) reactivation remains a life-threatening complication in recipients of a haploidentical haematopoietic stem cell transplantation (haploHSCT). Reconstitution of adaptive T lymphocytes is generally compromised at the early stages following transplant, suggesting an important role of other effector cells in preventing EBV infection. Our previous studies demonstrated that recovery of CD4 CD8 T cells negatively correlated with EBV reactivation after haploHSCT. In this prospective study on 132 adult patients with haematopoietic malignancy, recovery of T-cell subpopulations was characterized post-haploHSCT. We showed that the median counts of peripheral Vδ2 cells were continuously lower in recipients with EBV reactivation compared with controls at 30, 60 and 90 days after haploHSCT (P values: 0·006, <0·001 and 0·019, respectively). Landmark study further indicated that the cumulative incidence of EBV reactivation was significantly decreased in recipients with higher day-30 Vδ2 counts. Activation of Vδ2 cells upon EBV reactivation was accompanied by an induction of cell apoptosis. Cytotoxic effect of Vδ2 cells on EBV-infected cells was confirmed by in vitro experiments. Together, our findings uncovered a significant correlation of recovered Vδ2 with EBV reactivation following haploHSCT. These results will help to better understand the intrinsic anti-virus immunity and develop γδ T-based therapy strategies after haematopoietic transplantation.
[Mh] Termos MeSH primário: Infecções por Vírus Epstein-Barr/etiologia
Genes Codificadores da Cadeia delta de Receptores de Linfócitos T
Transplante de Células-Tronco Hematopoéticas
Herpesvirus Humano 4/fisiologia
Linfócitos T/metabolismo
Ativação Viral
[Mh] Termos MeSH secundário: Adolescente
Adulto
Apoptose/genética
Apoptose/imunologia
Citotoxicidade Imunológica
Infecções por Vírus Epstein-Barr/diagnóstico
Feminino
Doença Enxerto-Hospedeiro/etiologia
Doença Enxerto-Hospedeiro/prevenção & controle
Antígenos HLA/genética
Antígenos HLA/imunologia
Haplótipos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Seres Humanos
Incidência
Ativação Linfocitária/imunologia
Masculino
Meia-Idade
Linfócitos T/imunologia
Transplante Homólogo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (HLA Antigens)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.15037


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[PMID]:29266059
[Au] Autor:Tambur AR; Wiebe C
[Ad] Endereço:Transplant Immunology Laboratory, Comprehensive Transplant Center, Northwestern University, Chicago, IL.
[Ti] Título:HLA Diagnostics: Evaluating DSA Strength by Titration.
[So] Source:Transplantation;102(1S Suppl 1):S23-S30, 2018 01.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:HLA antibodies, and specifically donor-specific-HLA antibodies, play a key role in transplant-related diagnostics and decision-making. It is now clear that the simple differentiation between absence and presence of HLA donor-specific antibodies does not provide sufficient granularity in all clinical circumstances. It addition, knowledge of HLA antibody strength has potential utility at different stages of recipient evaluation along the transplant timeline from initial pretransplant evaluation, evaluation of a specific potential donor, and posttransplant monitoring for de novo donor-specific antibodies. Here we compare data evaluating HLA antibody strength using the conventional IgG-mean fluorescence intensity approach with serial dilution studies (titration) and of C1q binding (C1q-mean fluorescence intensity). The added value of titration studies along the 3 milestones of the transplant cycle is emphasized.
[Mh] Termos MeSH primário: Complemento C1q/imunologia
Imunofluorescência/métodos
Rejeição de Enxerto/imunologia
Antígenos HLA/imunologia
Teste de Histocompatibilidade/métodos
Imunoglobulina G/sangue
Isoanticorpos/sangue
[Mh] Termos MeSH secundário: Biomarcadores/sangue
Rejeição de Enxerto/prevenção & controle
Seres Humanos
Isoanticorpos/imunologia
Transplante de Órgãos
Assistência Perioperatória
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers); 0 (HLA Antigens); 0 (Immunoglobulin G); 0 (Isoantibodies); 80295-33-6 (Complement C1q)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001817


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[PMID]:29266058
[Au] Autor:Lan JH; Tinckam K
[Ad] Endereço:Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
[Ti] Título:Clinical Utility of Complement Dependent Assays in Kidney Transplantation.
[So] Source:Transplantation;102(1S Suppl 1):S14-S22, 2018 01.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Formation of antibodies against polymorphic HLA molecules on donor endothelium is central to the pathogenesis of antibody-mediated rejection, the dominant cause of long-term kidney allograft loss. Although introduction of the single-antigen bead assay has greatly facilitated the immune risk assessment of transplant recipients, it is recognized that not all IgG HLA antibodies detected using this method are equally relevant. In recent years, novel assays (C4d, C1q, C3d) have been developed to interrogate the complement-activating potential of anti-HLA antibodies in vitro, with the hypothesis that complement-fixing antibodies are more immediately injurious to the graft compared with noncomplement-binding antibodies. Although initial studies demonstrated the potential of these assays to risk-stratify antibodies beyond the conventional limited metric of mean fluorescence intensity values, new data from recent analyses challenge some of these early findings. In this review, we examine the technical aspects of these assays and key studies that evaluated the discriminant capacity of these tests to predict numerous outcomes in kidney transplantation. We discuss conflicting data and emerging controversies in the context of recent experimental evidence which offer new insights into the major factors that influence complement activation. Finally, we provide our perspective on the current role and utility of complement diagnostic assays as 1 variable in the multifactorial risk assessment and management of kidney transplant recipients.
[Mh] Termos MeSH primário: Ativação do Complemento/imunologia
Proteínas do Sistema Complemento/imunologia
Rejeição de Enxerto/imunologia
Antígenos HLA/imunologia
Teste de Histocompatibilidade/métodos
Isoanticorpos/metabolismo
Transplante de Rim
[Mh] Termos MeSH secundário: Biomarcadores/metabolismo
Rejeição de Enxerto/prevenção & controle
Seres Humanos
Isoanticorpos/imunologia
Medição de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers); 0 (HLA Antigens); 0 (Isoantibodies); 9007-36-7 (Complement System Proteins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001819


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[PMID]:29266057
[Au] Autor:Valenzuela NM; Schaub S
[Ad] Endereço:UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA.
[Ti] Título:The Biology of IgG Subclasses and Their Clinical Relevance to Transplantation.
[So] Source:Transplantation;102(1S Suppl 1):S7-S13, 2018 01.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Immunoglobulin G (IgG) is the dominant immunoglobulin and can be divided into 4 distinct subclasses. The evolution of IgG subclass switches is regulated by interaction with T cells and follows a 1-way direction (IgG3 → IgG1 → IgG2 → IgG4). Based on their structure, the 4 IgG subclasses can initiate different effector function such as complement activation, recruitment of various cells by Fc receptors, and agonistic signaling. Using current assays for HLA antibody detection as a template and replacing the generic reporter antibody with IgG subclass-specific reporter antibodies, it is possible to investigate the IgG subclasses of HLA antibodies. There are 15 different IgG subclass compositions possible. Based on the capability to activate the complement system and the class switch direction, 3 arbitrary patterns can be defined (ie, only complement-binding subclasses [IgG3 and/or IgG1], expansion to noncomplement-binding subclasses [IgG3 and/or IgG1 plus IgG2 and/or IgG4], and switch to noncomplement-binding subclasses [IgG2 and/or IgG4]). The latter group accounts for less than 5%, whereas the former 2 groups have a similar prevalence close to 50%. In the past 5 years, several studies correlated the IgG subclass pattern with occurrence of antibody-mediated rejection and allograft outcomes. Because of differences of the used IgG subclass assay, the time point of analyses, and the definition of outcomes, a clear picture has not emerged yet. Future needs are standardization of the assay, a more detailed knowledge of the initiated effector functions, and more well-designed clinical studies also looking at changes of the IgG subclass pattern over time.
[Mh] Termos MeSH primário: Antígenos HLA/imunologia
Teste de Histocompatibilidade
Switching de Imunoglobulina/imunologia
Imunoglobulina G/imunologia
Isoanticorpos/imunologia
Transplante de Órgãos
[Mh] Termos MeSH secundário: Ativação do Complemento/imunologia
Seres Humanos
Imunoglobulina G/classificação
Imunoglobulina G/genética
Isoanticorpos/classificação
Isoanticorpos/genética
Receptores Fc/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (HLA Antigens); 0 (Immunoglobulin G); 0 (Isoantibodies); 0 (Receptors, Fc)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001816


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[PMID]:29266056
[Au] Autor:Liwski RS; Gebel HM
[Ad] Endereço:Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
[Ti] Título:Of Cells and Microparticles: Assets and Liabilities of HLA Antibody Detection.
[So] Source:Transplantation;102(1S Suppl 1):S1-S6, 2018 01.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The evolution of antibody detection from cell- to bead-based technology has positively impacted the ability to allocate organs in a safe and timely manner. The devil, of course, is in the details that delineate how these assays are performed and applied and to recognize that while there have been some truly amazing technological advances (assets), they are still imperfect and subject to error (liabilities). This review identifies the strengths of HLA antibody assays, highlights their weaknesses and offers approaches for standardization.
[Mh] Termos MeSH primário: Micropartículas Derivadas de Células/imunologia
Antígenos HLA/imunologia
Teste de Histocompatibilidade/métodos
Isoanticorpos/metabolismo
[Mh] Termos MeSH secundário: Biomarcadores/metabolismo
Teste de Histocompatibilidade/normas
Seres Humanos
Transplante de Órgãos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers); 0 (HLA Antigens); 0 (Isoantibodies)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001818



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