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1.
Clin Transplant ; 38(5): e15338, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38762787

RESUMO

BACKGROUND: Kidney transplantation is the optimal treatment for end-stage renal disease. However, highly sensitized patients (HSPs) have reduced access to transplantation, leading to increased morbidity and mortality on the waiting list. The Canadian Willingness to Cross (WTC) program proposes allowing transplantation across preformed donor specific antibodies (DSA) determined to be at a low risk of rejection under the adaptive design framework. This study collected patients' perspectives on the development of this program. METHODS: Forty-one individual interviews were conducted with kidney transplant candidates from three Canadian transplant centers in 2022. The interviews were digitally recorded and transcribed for subsequent analyses. RESULTS: Despite limited familiarity with the adaptive design, participants demonstrated trust in the researchers. They perceived the WTC program as a pathway for HSPs to access transplantation while mitigating transplant-related risks. HSPs saw the WTC program as a source of hope and an opportunity to leave dialysis, despite acknowledging inherent uncertainties. Some non-HSPs expressed concerns about fairness, anticipating increased waiting times and potential compromise in kidney graft longevity due to higher rejection risks. Participants recommended essential strategies for implementing the WTC program, including organizing informational meetings and highlighting the necessity for psychosocial support. CONCLUSION: The WTC program emerges as a promising strategy to enhance HSPs' access to kidney transplantation. While HSPs perceived this program as a source of hope, non-HSPs voiced concerns about distributive justice issues. These results will help develop a WTC program that is ethically sound for transplant candidates.


Assuntos
Rejeição de Enxerto , Acessibilidade aos Serviços de Saúde , Falência Renal Crônica , Transplante de Rim , Listas de Espera , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Canadá , Falência Renal Crônica/cirurgia , Falência Renal Crônica/psicologia , Adulto , Rejeição de Enxerto/etiologia , Prognóstico , Seguimentos , Sobrevivência de Enxerto , Doadores de Tecidos/provisão & distribuição , Doadores de Tecidos/psicologia , Obtenção de Tecidos e Órgãos , Idoso , Isoanticorpos/imunologia
3.
Hum Immunol ; 85(3): 110768, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38433035

RESUMO

Despite its recent decline in volumes, intestinal transplantation remains an important option for patients with irreversible intestinal failures. The long-term outcome of an intestinal transplant has stagnated. The major cause of graft loss is rejection, resulting from mismatches in human leukocyte antigens (HLA) and the presence of antibodies to mismatched donor-specific HLA antigens (DSA). Literature has reported that DSAs, either preformed before transplantation or developed de novo after transplantation, are harmful to intestinal grafts, especially for those without combined liver grafts. A comprehensive assessment of DSA by the histocompatibility laboratory is critical for successful intestinal transplantation and its long-term survival. This paper briefly reviews the history and current status of different methods for detecting DSA and their clinical applications in intestinal transplantation. The focus is on applying different antibody assays to manage immunologically challenging intestinal transplant patients before and after transplantation. A clinical case is presented to illustrate the complexity of HLA tests and the necessity of multiple assays. The review of risk assessment by the histocompatibility laboratory also highlights the need for close interaction between the laboratory and the intestinal transplant program.


Assuntos
Rejeição de Enxerto , Antígenos HLA , Teste de Histocompatibilidade , Intestinos , Humanos , Antígenos HLA/imunologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/diagnóstico , Intestinos/transplante , Intestinos/imunologia , Medição de Risco , Teste de Histocompatibilidade/métodos , Isoanticorpos/imunologia , Isoanticorpos/sangue , Histocompatibilidade , Transplante de Órgãos/efeitos adversos , Sobrevivência de Enxerto/imunologia
4.
Am J Transplant ; 24(3): 362-379, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37871799

RESUMO

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training.


Assuntos
Transplante de Pâncreas , Transplante Homólogo , Biópsia , Isoanticorpos , Linfócitos T
5.
Vox Sang ; 118(12): 1105-1108, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37811680

RESUMO

BACKGROUND AND OBJECTIVES: Detection of anti-platelet antibodies is required for the diagnosis of foetal/neonatal alloimmune thrombocytopaenia. The most commonly used methods for anti-platelet antibody detection are the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and the Luminex bead assay (PakLx). However, for economic reasons, the use of the PakLx assay is limited. MATERIALS AND METHODS: In the present study, we evaluated the performance of an optimized protocol based on a half-volume of PakLx reagents. We compared two alternative procedures: one with a half-volume of all components including patient samples, and another based on a half-volume of reagents but a standard volume of patient sample. RESULTS: Our results obtained with a panel of 67 samples demonstrate improved sensitivity when using a standard sample volume. CONCLUSION: In the event of an inconclusive result with this optimized protocol (e.g., incomplete panel of positive Luminex beads), we recommend testing the sample with an alternative protocol (e.g., MAIPA or the original PakLx protocol).


Assuntos
Antígenos de Plaquetas Humanas , Recém-Nascido , Humanos , Análise Custo-Benefício , Isoanticorpos , Testes Imunológicos , Anticorpos Monoclonais , Plaquetas
6.
Am J Transplant ; 23(12): 1882-1892, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37543094

RESUMO

De novo donor-specific antibody (dnDSA) after renal transplantation has been shown to correlate with antibody-mediated rejection and allograft loss. However, the lack of proven interventions and the time and cost associated with annual screening for dnDSA are difficult to justify for all recipients. We studied a well-characterized consecutive cohort (n = 949) with over 15 years of prospective dnDSA surveillance to identify risk factors that would help institute a resource-responsible surveillance strategy. Younger recipient age and HLA-DR/DQ molecular mismatch were independent predictors of dnDSA development. Combining both risk factors into recipient age molecular mismatch categories, we found that 52% of recipients could be categorized as low-risk for dnDSA development (median subclinical dnDSA-free survival at 5 and 10 years, 98% and 97%, respectively). After adjustment, multivariate correlates of dnDSA development included tacrolimus versus cyclosporin maintenance immunosuppression (hazard ratio [HR], 0.37; 95% CI, 0.2-0.6; P < .0001) and recipient age molecular mismatch category: intermediate versus low (HR, 2.48; 95% CI, 1.5-4.2; P = .0007), high versus intermediate (HR, 2.56; 95% CI, 1.6-4.2; P = .0002), and high versus low (HR, 6.36; 95% CI, 3.7-10.8; P < .00001). When combined, recipient age and HLA-DR/DQ molecular mismatch provide a novel data-driven approach to reduce testing by >50% while selecting those most likely to benefit from dnDSA surveillance.


Assuntos
Rejeição de Enxerto , Tacrolimo , Humanos , Pré-Escolar , Criança , Tacrolimo/uso terapêutico , Análise Custo-Benefício , Estudos Prospectivos , Anticorpos , Antígenos HLA , Terapia de Imunossupressão , Fatores de Risco , Antígenos HLA-DR , Isoanticorpos/efeitos adversos , Sobrevivência de Enxerto , Estudos Retrospectivos
7.
Transfus Apher Sci ; 62(5): 103769, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37507272

RESUMO

Adsorption techniques are widely applied to detect underlying masked alloantibodies in warm autoimmune hemolytic anemia (WAIHA). We established various adsorption techniques with an aim to detect alloimmunization in WAIHA This study conducted over a period of nine years included 298 patients of WAIHA. Complete immunohematological evaluation was performed on these 298 samples following departmental protocols. Clinical and laboratory details of patients were obtained from patient files. Various adsorption methods were performed and statistically evaluated in the study. Out of 479 cases of autoimmune hemolytic anemia, WAIHA comprised of 62.2 % (N = 298). A total of 139 (46.6 %) serum samples revealed autoantibodies. Adsorption study was performed in 101 (72.7 %) indicated samples and 24 (23.8 %) of these showed 26 alloantibodies. Among the patients subjected to adsorption study hemolytic marker were significantly deranged in the alloimmunization group (p < 0.01). Polyethylene glycol (PEG) adsorption was the quickest (52.2-54.6 min) of all adsorption techniques with minimum (1.3-1.5) numbers of adsorptions needing for complete removal of serum antibodies. The LISS-papain (LP) technique was found to be more sensitive and specific compared to the other two techniques. The agreement between PEG adsorption and LP adsorption was found to be 'perfect' (96.4 %) with a Cohen's kappa (k) value of 0.9. We conclude that identification of alloantibody specificities underlying a warm autoantibody is critical for a safe and effective transfusion. All WAIHA patients with history of blood transfusion, pregnancy or both should be subjected to adsorption study. Selection of a suitable adsorption technique depends on multiple important factors.


Assuntos
Anemia Hemolítica Autoimune , Feminino , Gravidez , Humanos , Adsorção , Isoanticorpos , Eritrócitos , Autoanticorpos , Polietilenoglicóis
8.
Transfus Clin Biol ; 30(2): 219-227, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36608866

RESUMO

BACKGROUND AND AIM: Despite knowing benefits of extended phenotyping, a vast majority feel that phenotype matched units add to the cost of blood banking. The purpose of this study was to discuss advantages and disadvantages of performing Rh Kell phenotyping in Indian scenario. MATERIALS AND METHODS: This was a prospective, observational study conducted at a tertiary healthcare center between July 2014 and February 2020. All consecutive whole blood donors and all consecutive patients whose samples were sent for Rh-Kell phenotyping were included for calculating antigen, phenotype and gene frequencies. For rate of alloimmunization in patients transfused with phenotype matched units, all patients who were given Rh-Kell phenotype matched transfusions were included in the prophylactic antigen matched (PAM) category and those who were given random units were included in the non-PAM category. RESULTS: A total of 37,588 donors and 258 patients were included in the study for calculation of antigen, phenotype and gene frequencies. Percentage similarity of phenotypes between patient and donor populations was 33.8%. For rate of alloimmunization, results of a total of 31,991 patient samples revealed 0.94% prevalence of unexpected antibodies; highest against the Rh system. Three patients in the non-PAM category and one in the PAM category were alloimmunized during follow-up. Significant clinical and laboratory impact of phenotyping was observed in terms of reduced turnaround time and consumption of resources. CONCLUSION: Rh-Kell phenotyping of donors can prevent alloimmunization, reduce cost burden on the patient and the laboratory and help the laboratory personnel in smooth routine testing.


Assuntos
Transfusão de Sangue , Isoanticorpos , Humanos , Estudos Prospectivos , Doadores de Sangue , Armazenamento de Sangue
9.
Am J Transplant ; 23(1): 115-132, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36695614

RESUMO

Although anti-HLA (Human Leukocyte Antigen) donor-specific antibodies (DSAs) are commonly measured in clinical practice and their relationship with transplant outcome is well established, clinical recommendations for anti-HLA antibody assessment are sparse. Supported by a careful and critical review of the current literature performed by the Sensitization in Transplantation: Assessment of Risk 2022 working group, this consensus report provides clinical practice recommendations in kidney, heart, lung, and liver transplantation based on expert assessment of quality and strength of evidence. The recommendations address 3 major clinical problems in transplantation and include guidance regarding posttransplant DSA assessment and application to diagnostics, prognostics, and therapeutics: (1) the clinical implications of positive posttransplant DSA detection according to DSA status (ie, preformed or de novo), (2) the relevance of posttransplant DSA assessment for precision diagnosis of antibody-mediated rejection and for treatment management, and (3) the relevance of posttransplant DSA for allograft prognosis and risk stratification. This consensus report also highlights gaps in current knowledge and provides directions for clinical investigations and trials in the future that will further refine the clinical utility of posttransplant DSA assessment, leading to improved transplant management and patient care.


Assuntos
Isoanticorpos , Transplante de Rim , Humanos , Consenso , Antígenos HLA , Doadores de Tecidos , Antígenos de Histocompatibilidade Classe II , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Teste de Histocompatibilidade
10.
Am J Transplant ; 23(1): 133-149, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36695615

RESUMO

The Sensitization in Transplantation: Assessment of Risk workgroup is a collaborative effort of the American Society of Transplantation and the American Society of Histocompatibility and Immunogenetics that aims at providing recommendations for clinical testing, highlights gaps in current knowledge, and proposes areas for further research to enhance histocompatibility testing in support of solid organ transplantation. This report provides updates on topics discussed by the previous Sensitization in Transplantation: Assessment of Risk working groups and introduces 2 areas of exploration: non-human leukocyte antigen antibodies and utilization of human leukocyte antigen antibody testing measurement to evaluate the efficacy of antibody-removal therapies.


Assuntos
Transplante de Órgãos , Transplante de Órgãos/efeitos adversos , Fatores de Risco , Histocompatibilidade , Teste de Histocompatibilidade , Processos Grupais , Rejeição de Enxerto/etiologia , Isoanticorpos
11.
J Heart Lung Transplant ; 42(4): 423-432, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36702686

RESUMO

Immunological injury to the allograft, specifically by antibodies to de novo donor specific human leukocyte antigen (dnDSA) and antibody mediated injury and rejection are the major limitations to graft survival after heart transplantation (HT). As such, our approach to allosensitization remains limited by the inability of contemporaneous immunoassays to unravel pathogenic potential of dnDSA. Additionally, the role of dnDSA is continuously evaluated with emerging methods to detect rejection. Moreover, the timing and frequency of dnDSA monitoring for early detection and risk mitigation as well as management of dnDSA remain challenging. A strategic approach to dnDSA employs diagnostic assays to determine relevant antibodies in conjunction with clinical presentation and injury/rejection of allograft to tailor therapeutics. In this review, we aim to outline contemporary knowledge involving detection, monitoring and management of dnDSA after HT. Subsequently, we propose a diagnostic and therapeutic approach that may mitigate morbidity and mortality while balancing adverse reactions from pharmacotherapy.


Assuntos
Anticorpos , Transplante de Coração , Humanos , Adulto , Estudos Retrospectivos , Transplante de Coração/efeitos adversos , Antígenos HLA , Transplante Homólogo , Doadores de Tecidos , Sobrevivência de Enxerto , Rejeição de Enxerto , Isoanticorpos
12.
Transfusion ; 62(9): 1917-1922, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35904131

RESUMO

BACKGROUND: The Yt system consists of five antigens: antithetical Yta /Ytb and the high-prevalence antigens YTEG, YTLI, and YTOT. We investigated a sample from a Native American (NA) female with post-operative anemia and an unidentified antibody who developed rigors, tachycardia, and hypotension on transfusion of incompatible RBCs. METHODS AND MATERIALS: Serologic testing methods included LISS, PEG, and IgG gel. Test RBCs were treated with papain, trypsin, alpha-chymotrypsin, 2-amino-ethylisothiouronium, and dithiothreitol. Rare RBCs were tested, and inhibition studies were performed. DNA extracted from WBCs was used for Sanger sequencing. RESULTS: Initial testing showed strong 3-4+ plasma reactivity with all panel cells at LISS IAT; auto control was negative. Positive reactions were observed with numerous rare RBCs except for PNH-III, which lack GPI-linked DO, Yt, CROM, JMH, and Emm. Enzyme sensitivity patterns suggest Yt specificity, and soluble recombinant srYt neutralized reactivity. ACHE sequencing revealed YT*A/A genotype but with a homozygous change in exon 2, c.290A>G (p.Gln97Arg). Antibody reactivity was reminiscent of that seen in an unrelated NA male investigated previously. His RBCs were nonreactive with her plasma. ACHE carried the same c.290G/G change. CONCLUSION: Two unrelated NA patients were found to have an antibody to a new high-prevalence Yt antigen, designated YTGT (YT6), associated with a clinically significant transfusion reaction. Identification of the specificity relied on enzyme sensitivity, use of PNH-III RBCs, neutralization using soluble recombinant Yt, and the finding of a novel change in ACHE, c.290A>G (p.Gln97Arg), designated YT*01.-06. IVIG and steroids were used to mitigate further reactions to transfusion.


Assuntos
Antígenos de Grupos Sanguíneos , Isoanticorpos , Antígenos de Grupos Sanguíneos/genética , Transfusão de Sangue , Feminino , Humanos , Masculino , Prevalência , Indígena Americano ou Nativo do Alasca
13.
J Korean Med Sci ; 37(22): e177, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668687

RESUMO

BACKGROUND: In lung transplantation, human leukocyte antigen (HLA) compatibility is not included in the lung allocation score system or considered when placing donor allografts. However, HLA matching may affect the outcomes of lung transplantation. This study evaluated the current assessment status, prevalence, and effects of HLA crossmatching in lung transplantation in Korean patients using nationwide multicenter registry data. METHODS: Two hundred and twenty patients who received lung transplantation at six tertiary hospitals in South Korea between March 2015 and December 2019 were retrospectively reviewed. Clinical data, including general demographic characteristics, primary diagnosis, and pretransplant status of the recipients and donors registered by the Korean Organ Transplant Registry, were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier method with log-rank tests. RESULTS: Complement-dependent cytotoxic crossmatch (CDC-XM) was performed in 208 patients (94.5%) and flow cytometric crossmatch (flow-XM) was performed in 125 patients (56.8%). Among them, nine patients (4.1%) showed T cell- and/or B cell-positive crossmatches. The incidences of postoperative complications, including primary graft dysfunction, acute rejection, and chronic allograft dysfunction in positively crossmatched patients, were not significant compared with those in patients without mismatches. Moreover, Kaplan-Meier analyses showed poorer 1-year survival in patients with positive crossmatch according to CDC-XM (P < 0.001) and T lymphocyte XM (P = 0.002) than in patients without mismatches. CONCLUSION: Positive CDC and T lymphocyte crossmatching results should be considered in the allocation of donor lungs. If unavailable, the result should be considered for postoperative management in lung transplantation.


Assuntos
Transplante de Rim , Transplante de Pulmão , Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto , Antígenos HLA , Teste de Histocompatibilidade/métodos , Humanos , Isoanticorpos , Estudos Retrospectivos
14.
Blood Adv ; 6(18): 5267-5278, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-35404997

RESUMO

Administration of ex vivo expanded somatic myeloid progenitors has been explored as a way to facilitate a more rapid myeloid recovery and improve overall survival after myeloablation. Recent advances in induced pluripotent stem cell (iPSC) technologies have created alternative platforms for supplying off-the-shelf immunologically compatible myeloid progenitors, including cellular products derived from major histocompatibility complex (MHC) homozygous superdonors, potentially increasing the availability of MHC-matching cells and maximizing the utility of stem cell banking. However, the teratogenic and tumorigenic potential of iPSC-derived progenitor cells and whether they will induce alloreactive antibodies upon transfer remain unclear. We evaluated the safety and efficacy of using CD34+CD45+ hematopoietic progenitors derived from MHC homozygous iPSCs (iHPs) to treat cytopenia after myeloablative hematopoietic stem cell (HSC) transplantation in a Mauritian cynomolgus macaque (MCM) nonhuman primate (NHP) model. We demonstrated that infusion of iHPs was well tolerated and safe, observing no teratomas or tumors in the MCMs up to 1 year after HSC transplantation and iHP infusion. Importantly, the iHPs also did not induce significant levels of alloantibodies in MHC-matched or -mismatched immunocompetent MCMs, even after increasing MHC expression on iHPs with interferon-γ. These results support the feasibility of iHP use in the setting of myeloablation and suggest that iHP products pose a low risk of inducing alloreactive antibodies.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Células-Tronco Pluripotentes Induzidas , Animais , Antígenos CD34 , Interferon gama , Isoanticorpos , Macaca fascicularis , Complexo Principal de Histocompatibilidade
15.
Transplant Proc ; 54(4): 968-971, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35277257

RESUMO

BACKGROUND: Antibody-mediated rejection (AMR) remains challenging in kidney transplant recipients. It may negatively impact the graft survival, and its treatment is associated to relatively high expenses. The aim of our study was to assess the costs of treatment of acute AMR in the Polish settings. METHODS: A total of 11 kidney transplant recipients with acute AMR diagnosed between September 2016 and August 2019 and treated in our center were included. Direct costs of inpatient and outpatient care in the first year after AMR diagnosis from the perspective of a transplant center were retrospectively calculated. RESULTS: The costs of treatment of acute AMR were considerably high, with a mean 1-month cost of treatment 12,718 PLN (∼€2925; ∼3307 US dollars). That means that costs of management of kidney transplant recipients with acute AMR are almost 2-fold higher than hemodialysis. Intravenous immunoglobulin was responsible for the majority (55%) of costs. CONCLUSIONS: Treatment of acute AMR increases the costs of post-kidney transplant care in involved patients. Therefore, efforts should be made to minimize the risk for acute AMR. Despite its potential clinical benefits, management of acute AMR is even more expensive than dialysis. Therefore, further cost-effectiveness analyses are needed to justify the spending and to establish the best treatment regimens.


Assuntos
Transplante de Rim , Anticorpos , Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto , Humanos , Isoanticorpos , Transplante de Rim/efeitos adversos , Diálise Renal , Estudos Retrospectivos
16.
Am J Transplant ; 22(3): 698-704, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34379882

RESUMO

Women with advanced lung disease, particularly Black and Hispanic women, are more likely than other patients to have anti-human leukocyte (HLA) antibodies against potential donors. Sensitized patients, especially those who are highly sensitized, are less likely to be listed for lung transplant or to be considered candidates for mechanical circulatory support. They are also at higher risk for waitlist death. Institutional variability in approach to HLA antibody screening and pre-transplant management creates barriers to transplant that disproportionately impact Black and Hispanic women. At the same time, our understanding of the clinical significance of pre-transplant antibodies lags behind the sophistication of our screening assays. The lack of national data on pre- and post-transplant HLA antibody characteristics hinders research into strategies to mitigate concerns about these antibodies and to improve access to lung transplant among sensitized patients. Ongoing work should be done to identify clinically higher risk antibodies, to develop better strategies for safely crossing antibodies at the time of transplant, and to model changes in lung allocation to give priority to sensitized patients for a HLA antibody-antigen compatible donors. These priorities mandate a commitment to collaborative, multicenter research and to real time translation of results to clinical practice and allocation policy.


Assuntos
Equidade em Saúde , Transplante de Pulmão , Feminino , Antígenos HLA , Teste de Histocompatibilidade , Humanos , Isoanticorpos , Transplante de Pulmão/efeitos adversos
17.
Lab Med ; 53(1): 53-57, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34350958

RESUMO

OBJECTIVE: Performing autocontrol with a reflex direct antiglobulin test (DAT) or directly performing IgG DAT only for alloantibody detection has been a matter of institutional preference. The aim of this study is to evaluate antibody identification (ABID), local cost, and staff time savings of both processes. METHODS: We retrospectively reviewed all positive indirect antiglobulin tests with corresponding ABID, DAT, autocontrol, and patients with newly identified antibodies in 2014 and 2016. The number of tests performed, ABID, and the cost differences between methods were compared. Cost analysis was estimated from direct material costs, labor costs, and time spent per ABID workup. RESULTS: Annual costs and time saved by performing direct IgG DAT only were $8460 and 180 hours, respectively. The percentage of new ABID in 2014 and 2016 was identical (3.3%). CONCLUSION: Removing autocontrol with reflex DATs at our center reduced costs and staff time while maintaining a comparable rate of positivity of ABID.


Assuntos
Reflexo , Teste de Coombs , Análise Custo-Benefício , Humanos , Imunoglobulina G , Isoanticorpos , Estudos Retrospectivos
18.
Front Immunol ; 12: 687715, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177940

RESUMO

The outcome of organ transplantation is largely dictated by selection of a well-matched donor, which results in less chance of graft rejection. An allogeneic immune response is the main immunological barrier for successful organ transplantation. Donor and recipient human leukocyte antigen (HLA) mismatching diminishes outcomes after solid organ transplantation. The current evaluation of HLA incompatibility does not provide information on the immunogenicity of individual HLA mismatches and impact of non-HLA-related alloantigens, especially in vivo. Here we demonstrate a new method for analysis of alloimmune responsiveness between donor and recipient in vivo by introducing a humanized mouse model. Using molecular, cellular, and genomic analyses, we demonstrated that a recipient's personalized humanized mouse provided the most sensitive assessment of allogeneic responsiveness to potential donors. In our study, HLA typing provided a better recipient-donor match for one donor among two related donors. In contrast, assessment of an allogeneic response by mixed lymphocyte reaction (MLR) was indistinguishable between these donors. We determined that, in the recipient's humanized mouse model, the donor selected by HLA typing induced the strongest allogeneic response with markedly increased allograft rejection markers, including activated cytotoxic Granzyme B-expressing CD8+ T cells. Moreover, the same donor induced stronger upregulation of genes involved in the allograft rejection pathway as determined by transcriptome analysis of isolated human CD45+cells. Thus, the humanized mouse model determined the lowest degree of recipient-donor alloimmune response, allowing for better selection of donor and minimized immunological risk of allograft rejection in organ transplantation. In addition, this approach could be used to evaluate the level of alloresponse in allogeneic cell-based therapies that include cell products derived from pluripotent embryonic stem cells or adult stem cells, both undifferentiated and differentiated, all of which will produce allogeneic immune responses.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Histocompatibilidade , Leucócitos Mononucleares/transplante , Transplante de Órgãos , Baço/imunologia , Tolerância ao Transplante , Animais , Linfócitos T CD8-Positivos/metabolismo , Células Cultivadas , Bases de Dados Genéticas , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Sobrevivência de Enxerto , Antígenos HLA/genética , Humanos , Isoanticorpos/metabolismo , Leucócitos Mononucleares/imunologia , Teste de Cultura Mista de Linfócitos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Órgãos/efeitos adversos , Fenótipo , Valor Preditivo dos Testes , Baço/metabolismo , Transcriptoma , Transplante Homólogo
19.
Hum Immunol ; 82(4): 302-308, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33744026

RESUMO

INTRODUCTION: Flow cytometric crossmatch assay (FCXM) is a sensitive cell-based method for evaluating the presence of donor-specific antibodies (DSA) before transplantation. Recently, 96-well tray FCXM protocol (Halifax FCXM) with improved test efficiency has been introduced. The objective of the present study was to assess the performance of Halifax FCXM by correlating with DSA results based on single antigen bead (SAB) assays (virtual crossmatch, VXM). METHODS: A total of 341 FCXMs were evaluated for the detection of HLA-DSA. A positive VXM was defined as having at least one HLA - DSA (HLA-A, B, Cw, DR, DQB1) with ≥ 1000 MFI (mean fluorescence intensity) identified by SAB assay. RESULTS: Of a total 341 cases, 113 showed class I VXM (+) with class I DSA MFI ≥ 1000 exclusively against one or more donor HLA class I antigens (HLA-A, B, Cw), 72 had class I-/II + DSA, and 156 had VXM(-). Halifax T-FCXM showed a sensitivity of 87.6% (99/113) and a specificity of 98.2% (224/228) for detecting class I VXM (+). The concordance between T-FCXM and class I VXM was 94.7% (323/341). Halifax B-FCXM showed a sensitivity of 58.3% (42/72) and a specificity of 98.7% (154/156) for detecting class I-/II + DSAs. The concordance between B-FCXM and class I-/II + VXM was 86.0% (196/228). When we separately analyzed data, B-FCXM detected HLA-DR (+) (68.8%) and HLA-DQ (+) DSAs (71.0%) similarly (P > 0.05). T-FCXM detected 87.6%, 97.2%, and 98.2% of class I DSA-positive cases with MFI values (sumDSA) ≥ 1000, ≥ 3000, and ≥ 5000, respectively. B-FCXM detected 58.3% of class I-II + DSA -positive (≥1000) cases, but detected 76.7% (33/43) and 89.2% (33/37) of class I-II + DSAs if MFI values of sumDSA and immunodominant DSA (iDSA) were above 5000, respectively. Halifax FCXM had sensitivities of 91.5% and 96.2% for detecting VXM (+) having MFI values above 5000 for class I or class II sumDSA and iDSA, respectively. CONCLUSION: Halifax FCXM showed a good correlation, especially with SAB assay-based high MFI DSA or sumDSA. Concurrent application of FCXM with VXM can improve pre-transplant risk assessment and progress organ allocation efficiency.


Assuntos
Rejeição de Enxerto/imunologia , Antígenos HLA/genética , Teste de Histocompatibilidade/métodos , Isoanticorpos/sangue , Transplante de Rim , Transplante de Fígado , Citometria de Fluxo , Antígenos HLA/metabolismo , Humanos , Estudos Retrospectivos , Sensibilidade e Especificidade
20.
Transfusion ; 61(7): 2019-2024, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33745158

RESUMO

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


Assuntos
Transfusão de Sangue Intrauterina/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Histocompatibilidade Materno-Fetal/imunologia , Troca Materno-Fetal/imunologia , Aborto Espontâneo/etnologia , Adulto , Estudos de Coortes , Conjuntos de Dados como Assunto , Emigrantes e Imigrantes/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Feminino , Disparidades em Assistência à Saúde/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Humanos , Imunoglobulina G/imunologia , Isoanticorpos/sangue , Isoanticorpos/imunologia , Paridade , Gravidez , Grupos Raciais/estatística & dados numéricos , Imunoglobulina rho(D)/sangue , São Francisco , Classe Social
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