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Clinically significant alloantibody

Sean Agbor-Enoh, Annette M Jackson, Ilker Tunc, Gerald J Berry, Adam Cochrane, David Grimm, Andrew Davis, Pali Shah, Anne W Brown, Yan Wang, Irina Timofte, Palak Shah, Sasha Gorham, Jennifer Wylie, Natalie Goodwin, Moon Kyoo Jang, Argit Marishta, Kenneth Bhatti, Ulgen Fideli, Yanqin Yang, Helen Luikart, Zeling Cao, Mehdi Pirooznia, Jun Zhu, Charles Marboe, Aldo Iacono, Steven D Nathan, Jonathan Orens, Hannah A Valantine, Kiran Khush
BACKGROUND: Antibody-mediated rejection (AMR) often progresses to poor health outcomes in lung transplant recipients (LTRs). This, combined with the relatively insensitive clinical tools used for its diagnosis (spirometry, histopathology) led us to determine whether clinical AMR is diagnosed significantly later than its pathologic onset. In this study, we leveraged the high sensitivity of donor-derived cell-free DNA (ddcfDNA), a novel genomic tool, to detect early graft injury after lung transplantation...
January 31, 2018: Journal of Heart and Lung Transplantation
Shaun Lawicki, Emily A Coberly, Laura A Lee, Mary Johnson, Quentin Eichbaum
BACKGROUND: The Kidd-null phenotype, Jk(a-b-), occurs in individuals who do not express the JK glycoprotein. Jk(a-b-) individuals can make an antibody against the Jk3 antigen, a high-incidence antigen present in more than 99.9% of most populations. This presents many challenges to the blood bank including identification of the antibody, masking of other antibodies, and how to provide transfusion support given the rarity of Jk3-negative blood products. Kidd antibodies may cause acute and delayed hemolytic reactions as well as hemolytic disease of the fetus and newborn (HDFN)...
February 25, 2018: Transfusion
Hang Quach, Simon Benson, Helen Haysom, Anne-Marie Wilkes, Nicole Zacher, Merrole Cole-Sinclair, Henry Miles Prince, Peter Mollee, Andrew Spencer, Phoebe Joy Ho, Simon J Harrison, Cindy Lee, Bradley Augustson, James Daly
In recent years, the anti-CD38 monoclonal antibody daratumumab (Darzalex; Janssen-Cilag Pty Ltd) has been shown to be highly efficacious in relapsed and refractory multiple myeloma, with the final results of treatment in newly diagnosed patients awaited. Despite awareness of the potential interference of daratumumab in pre-transfusion immunohaematology testing during phase I and II clinical studies, there was a degree of unpreparedness in the community upon the introduction of this drug into the clinics, particularly the impact that it has on the operational processes in hospital transfusion laboratories and timely issue of red blood cells (RBCs)...
February 2018: Internal Medicine Journal
Pauline Balkaransingh, Guy Young
The evolution of hemophilia treatment and care is a fascinating one but has been fraught with many challenges at every turn. Over the last 50 years or so patients with hemophilia and providers have witnessed great advances in the treatment of this disease. With these advances, there has been a dramatic decrease in the mortality and morbidity associated with hemophilia. Even with the remarkable advancements in treatment, however, new and old challenges continue to plague the hemophilia community. The cost of factor replacement and the frequency of infusions, especially in patients with severe hemophilia on prophylaxis, remains a significant challenge for this population...
February 2018: Therapeutic Advances in Hematology
K Tam, I Tang, J Ho, W Yeung, C K Lee, P Ip, J Kwok
BACKGROUND: Alloantibodies against human neutrophil antigens (HNA) are associated with a variety of clinical conditions. Over the past decade, the allelic and genotypic frequencies of the five HNA systems have been evaluated. Although the HNA system is less polymorphic than human leukocyte antigens (HLA), significant differences in the genotypic and allele frequencies still exist in different populations, even those living in close proximity. OBJECTIVES: To delineate HNA genotypic and allele frequencies to provide vital information on estimating the risk of HNA-associated diseases for our local population...
December 27, 2017: Transfusion Medicine
Lauren Andersson, Ferenc Szabo
BACKGROUND: Haemolytic disease of the fetus/newborn secondary to clinically significant non-Rhesus-D antibodies has risen in importance since the advent of immunoprophylactic anti-D administration to Rhesus-D negative women. Of interest is the incidence of these antibodies in Rhesus-D positive women, who receive less frequent antenatal alloantibody screening. This is of particular concern if the antibodies arise late in pregnancy and may go undetected. AIMS: To assess the proportion of Rhesus-D positive pregnant women with late developing clinically significant antibodies for haemolytic disease of the fetus/newborn, and whether these resulted in adverse fetal outcomes...
November 28, 2017: Australian & New Zealand Journal of Obstetrics & Gynaecology
Feifei Qiu, Huazhen Liu, Chun-Ling Liang, Golay D Nie, Zhenhua Dai
Due to vigorous alloimmunity, an allograft is usually rejected without any conventional immunosuppressive treatment. However, continuous global immunosuppression may cause severe side effects, including tumors and infections. Mounting evidence has shown that cyclosporine (CsA), a common immunosuppressant used in clinic, impedes allograft tolerance by dampening regulatory T cells (Tregs), although it inhibits allograft rejection at the same time. Therefore, it is necessary to seek an alternative immunosuppressive drug that spares Tregs with high efficiency in suppression but low toxicity...
2017: Frontiers in Immunology
Elizabeth S Allen, Kshitij Srivastava, Matthew M Hsieh, Courtney D Fitzhugh, Harvey G Klein, John F Tisdale, Willy A Flegel
BACKGROUND: Haemopoietic progenitor cell (HPC) transplantation can cure sickle cell disease. Non-myeloablative conditioning typically results in donor-derived erythrocytes and stable mixed chimerism of recipient-derived and donor-derived leucocytes. Exposure to donor antigens from the HPC graft and new red cell antibodies induced by transfusion can lead to immunohaematological complications. We assessed the incidence of such complications among HPC transplant recipients with sickle cell disease...
November 2017: Lancet Haematology
X Liao, H Li, W Jiao, C Zhu, W Wang, Z Mo, Z Yang, Z Zhu
Individuals with the human neutrophil antigen (HNA)-3b/3b type can produce HNA-3a antibodies, which have been reported to cause severe, sometimes fatal transfusion-related acute lung injury (TRALI). Our study aimed to determine the genotype frequency of HNA-3a/3b which will be helpful to estimate the potential risk for forming anti-HNA-3a, the clinically relevant antibody linked to TRALI in two different ethnic groups of southern China. Five hundred unrelated and healthy blood donors (284 male, 216 female; 300 Zhuangs, 200 Dongs) from the Guangxi Zhuang Autonomous Region were simultaneously typed for the HNA-3 allele using a polymerase chain reaction sequence-based typing (PCR-SBT) method...
October 22, 2017: International Journal of Immunogenetics
Deepak Singhal, Monika M Kutyna, Rakchha Chhetri, Li Yan A Wee, Sophia Hague, Lakshmi Nath, Shriram V Nath, Romi Sinha, Nicholas Wickham, Ian D Lewis, David M Ross, Peter G Bardy, Luen Bik To, John Reynolds, Erica M Wood, David J Roxby, Devendra K Hiwase
Up to 90% of patients with a myelodysplastic syndrome require red blood cell transfusion; nevertheless, comprehensive data on red cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registered in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%...
December 2017: Haematologica
Jorge Bartolucci, Fernando J Verdugo, Paz L González, Ricardo E Larrea, Ema Abarzua, Carlos Goset, Pamela Rojo, Ivan Palma, Ruben Lamich, Pablo A Pedreros, Gloria Valdivia, Valentina M Lopez, Carolina Nazzal, Francisca Alcayaga-Miranda, Jimena Cuenca, Matthew J Brobeck, Amit N Patel, Fernando E Figueroa, Maroun Khoury
RATIONALE: Umbilical cord-derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow-derived mesenchymal stem cells have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction, no clinical trial has evaluated intravenous infusion of UC-MSCs in these patients...
October 27, 2017: Circulation Research
Jeffrey S Jhang, Richard O Francis, Anne Winkler, Christopher Tormey
Transfusion medicine (TM) physicians provide medical services that benefit all patients such as providing 24-hour laboratory coverage, advising health care providers on test interpretation and selection, validating new methods, and supervising technical personnel. These services ensure delivery of accurate, reliable, and timely laboratory test results and blood products. TM physicians also provide consultations to individual patients by 1) interpreting and determining the clinical significance of test results (e...
October 2017: Transfusion
V B Oliveira, M R Dezan, F C A Gomes, S F Menosi Gualandro, J E Krieger, A C Pereira, J D Marsiglia, J E Levi, V Rocha, A Mendrone-Junior, E C Sabino, C L Dinardo
Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) molecule is expressed on T-lymphocyte membrane and negatively influences the antigen-presenting process. Reduced expression of CTLA-4 due to gene polymorphisms is associated with increased risk of autoimmune disorders, whose physiopathology is similar to that of post-transfusion red blood cell (RBC) alloimmunization. Our goal was to evaluate if polymorphisms of CTLA-4 gene that affect protein expression are associated with RBC alloimmunization. This was a case-control study in which 134 sickle cell disease (SCD) patients and 253 non-SCD patients were included...
October 2017: International Journal of Immunogenetics
R N Makroo, Sweta Nayak, Mohit Chowdhry, Prashant Karna
We have analyzed the method used in our laboratory to detect the most elusive, clinically significant alloantibody: the Kidd alloantibodies and find the most convenient procedure. A retrospective analysis of the method used in our laboratory for determining Kidd alloantibodies from January 2013 to May 2015 was conducted. The details of the event that sensitized the patient for red cell antibody formation and procedure used to detect the alloantibody were retrieved from the departmental records. Of 405 red cell antibody identification cases, 24 (5...
June 2017: Indian Journal of Hematology & Blood Transfusion
Marina C A V Conrado, Amanda N D'Avila, Juliana B Vieira, Silvia L Bonifacio, Francisco C A Gomes, Marcia R Dezan, Valeria B Oliveira, Ingrid H Ribeiro, Luciana T C M Tucunduva, Alfredo Mendrone-Júnior, Vanderson Rocha, Carla L Dinardo
BACKGROUND: The Monocyte Monolayer Assay (MMA) is an in vitro simulation of red blood cell (RBC) alloantibody behavior. It has been classically applied to predict the risks of post-transfusion hemolytic reactions when transfusing incompatible RBC units. Quantifying erythrophagocytosis by MMA may be an interesting option for situations where there is doubt whether a RBC autoantibody is mediating significant hemolysis. Here, we present three situations involving RBC autoantibodies in which the MMA was decisive for clarifying the diagnosis and choosing the best clinical treatment...
May 31, 2017: Journal of Clinical Laboratory Analysis
M Leisch, L Weiss, N Lindlbauer, C Jungbauer, A Egle, E Rohde, R Greil, C Grabmer, L Pleyer
Alloimmunization to Red Blood Cell (RBC) antigens frequently occurs in patients with myeloid neoplasms (AML, MDS and CMML) and potentially poses the patient at risk for delayed hemolytic transfusion reactions and limited supply of compatible RBC-units. However, there is comparatively little data on transfusion associated characteristics in this patient cohort. We therefore retrospectively analyzed transfusion requirements and clinical outcomes of 184 patients with myloid neoplasms treated with azacitidine at the Paracelsus Medical University Salzburg, which were included in the Austrian Registry of Hypomethylating Agents...
August 2017: Leukemia Research
Daljit Kaur, Lovenish Bains, Manoj Kandwal, Indu Parmar
INTRODUCTION: The ultimate aim of pretransfusion testing is the acceptable survival of donor red cells in recipient's body and antibody detection plays a critical role in achieving the same. The cornerstone of antibody detection method is detecting an unexpected antibody as against the expected antibodies of ABO blood group system. Autoantibodies can also interfere with the detection of clinically significant alloantibodies. AIM: To study the frequency of alloantibodies and autoantibodies in the healthy blood donors and patient population visiting our hospital...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
Lerisa Govender, Jean-Christophe Wyss, Rajesh Kumar, Manuel Pascual, Dela Golshayan
In recent years, regulatory T cells (Treg)-based immunotherapy has emerged as a promising strategy to promote operational tolerance after solid organ transplantation (SOT). However, a main hurdle for the therapeutic use of Treg in transplantation is their low frequency, particularly in non-lymphopenic hosts. We aimed to expand Treg directly in vivo and determine their efficacy in promoting donor-specific tolerance, using a stringent experimental model. Administration of the IL-2/JES6-1 immune complex at the time of transplantation resulted in significant expansion of donor-specific Treg, which suppressed alloreactive T cells...
2017: Frontiers in Immunology
Patricia A R Brunker, Keerthana Ravindran, R S Shirey
Alloimmunization to red blood cell antigens is unpredictable and poorly understood. Patients who are negative for high-incidence antigens (HIAs) are at risk for developing the corresponding antibodies. Molecular methods can easily predict the lack of an antigen and thus, the risk of an individual to become immunized. We examined the prevalence and risk factors for HIA alloimmunization in patients at risk based on genotyping results. Genotyping using a molecular method (HEA BeadChip™, Immucor, Warren, NJ) was performed on all patient specimens referred for molecular testing over 45 months; serologic and clinical data were analyzed...
January 2017: Immunohematology
Andrea M Olofson, Rachael M Chandler, Cynthia R Marx-Wood, Craig A Babcock, Nancy M Dunbar
BACKGROUND: Automated solid-phase antibody screening uses red blood cell (RBC) membranes immobilised on polystyrene test wells to detect RBC specific antibodies. Despite its time-saving and labour-saving benefits, this method produces a higher rate of nonspecific reactivity compared with manual screening. Solid-phase panreactivity (SPP) is characterised by panreactivity (ie, all test cells reacting) in solid-phase testing accompanied by a negative autocontrol and a lack of reactivity when the same screening cells are tested in tube...
November 2017: Journal of Clinical Pathology
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