scholarly journals Urgent Transfusion in a New Patient with Rare Blood Type

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 28-28
Author(s):  
Catherine Dubé ◽  
Scherzinger Kritikopoulos ◽  
Marsha Downie ◽  
Elizabeth Krok ◽  
Katerina Pavenski
Keyword(s):  
B Cells ◽  
Blood Group ◽  
Research Funding ◽  
Antigen Expression ◽  
Cord Compression ◽  
Positive Control ◽  
Blood Type ◽  
Patient Specimen ◽  
Field Reaction ◽  
Clinically Significant

Background/Case Studies: Bombay is a rare blood group characterized by the absence of H substance at the surface of RBCs leading to naturally occurring anti-H antibodies. Anti-H presents the risk of severe hemolytic transfusion reactions in these patients. The case presented is of a 32-year-old female of Middle Eastern origin, who presented with a traumatic vertebral fracture with spinal cord compression and required urgent neurosurgery. Her presenting hemoglobin was 84 g/L. She had no previous group and screen on record, had never been transfused and had a history of a remote miscarriage. Study Design/Methods: Forward blood group with an automated gel-method instrument revealed the following reactions: negative with anti-A, unable to interpret (?) with anti-B, 4+ with anti-D. Reverse grouping revealed the following reactions: 4+ with A1-cells and an unexpected 1+ with B-cells. The antibody screen and 11 cell panel in gel (Micro Typing Systems) 2+; the panel, with enhancement reacted 3+ in Ficin. The auto control was negative. A second panel and pre-warm panel produced the same findings. An antibody reacting at 37C against a high-frequency antigen was suspected. Patient specimen was sent for investigation to the reference lab (RL), which performed blood group by manual tube test, antibody identification with panels by manual tube PEG-IAT method; RL also sent a sample for ABH sequencing (Sanger). Results/Findings: A thawed frozen plasma sample from a previous Bombay patient 12 years prior showed no reactivity against the patient's RBCs; positive control included. A frozen Bombay RBC unit was ordered urgently from the blood supplier and was crossmatch compatible. The patient underwent surgery and was transfused with a single unit of RBC for peri-operative bleeding. She was treated with erythropoietin and IV iron post-operatively and did not require any further transfusions. The investigation at the RL showed mixed field reaction on forward blood typing with anti-B and anti-A,B and negative reaction with anti-A commercial reagents. The RL reverse grouping showed 4+ with all O H+ and A1 red cells, but 2+ with B cells. The autocontrol and group O H- cells did not react, confirming anti-H and suggesting Para-Bombay group. ABH sequencing revealed a normal B allele (ABO*B.01) while genotyping of FUT1 revealed a null allele (FUT1*01N.12) and weak H allele (FUT1*01W.23). FUT2 genotyping (FUT2*01N.02) predicted a nonsecretor (sese) phenotype. Conclusions: This patient with non-secretor status, variant H production, clinically significant anti-H, greatly reduced B antigen expression, should be treated as a Bombay (Oh) for transfusion purposes. She was counselled and provided with an antibody card and a letter. This case illustrates the importance of timely communication with the clinical team about the risks and benefits of transfusion pending antibody identification, as it could have proved fatal in this case. Figure Disclosures Pavenski: Bioverativ:Research Funding;Shire/Takeda:Honoraria;Octapharma:Research Funding;Alexion:Honoraria, Research Funding;Sanofi:Research Funding;Ablynx/Sanofi:Honoraria, Research Funding.

scholarly journals Combinatorial Targeting of Multiple Shared Antigens By Adapter-CAR-T Cells (aCAR-Ts) Allows Target Cell Discrimination and Specific Lysis Based on Differential Expression Profiles

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4543-4543 ◽  
Author(s):  
Christian M. Seitz ◽  
Verena Kieble ◽  
Clara Illi ◽  
Selina Reiter ◽  
Stefan Grote ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Target Cell ◽  
Research Funding ◽  
Expression Profiles ◽  
Antigen Expression ◽  
Cell Lysis ◽  
Target Antigen ◽  
Activation Threshold ◽  
Car T

Abstract Despite tremendous clinical success of chimeric antigen receptor (CAR) expressing T cell (CAR-T) therapies, targeting B-phenotypic antigens in ALL, CLL, NHL or multiple myeloma, there are still major limitations for broader clinical application. CAR-Ts are capable to generate a specific immune response against defined surface-expressed antigens leading to sustained depletion of target antigen expressing tissues e.g. B cells. While B cell function can be substituted by repetitive IgG infusions, prolonged depletion of vitally essential tissues is not compatible with life. In AML for instance, most promising target antigens are expressed along myeloid lineage differentiation, limiting the therapeutic applicability. Therefore, CAR-Ts targeting essential shared antigens must allow tight regulation of CAR-T function and/or be able to differentiate between cancerous and healthy tissue. To address these issues, we have developed the adapter CAR-T cell (aCAR-T) system. By splitting antigen recognition and CAR-T activation, introducing adapter molecules (AMs), the system allows precise quantitative (on-/off-switch) as well as qualitative (change and combine target antigens) regulation of CAR-T function. aCAR-Ts are based on the unique properties of a novel scFv targeting a "neo"-epitope-like structure consisting of the endogenous vitamin biotin in the context of a specific linker, referred to as linker-label-epitope (LLE). LLEs can be easily conjugated to novel or preexisting AM formats like monoclonal antibodies (mAbs) or mAb fragments in a GMP-compliant manner. We were able to demonstrate that aCAR-Ts allow simultaneous targeting of various antigens ("OR"-gate) , preventing antigen evasion by selection of antigen or epitope-loss variants. In the present study we intended to investigate whether aCAR-Ts are capable to identify and differentiate target cells due to versatile antigen expression profiles ("AND"-gate). In theory, AMs against different target antigens can be assembled on the surface of a target cell , leading to aCAR-T activation independent of the targeted antigens (surface painting) , by binding to the presented LLE-tags. Therefore, combinatorial AMs treatment might allow to translate complex and multiple antigen-dependent target cell identification into an aCAR-T activation. To test this hypothesis, we have generated LLE-AMs against ALL/NHL - (CD10, CD19, CD20, CD22, CD37, CD138, ROR1) and AML - (CD32, CD33, CD38, CD123, CD135, CD305, CLL1) associated antigens. Individual threshold concentrations for aCAR-T activation by different AMs, targeti ng the model cell lines Nalm 6 (ALL), JeKo1 (NHL), HL-60 , U973 and Molm13 ( all AML), have been analyzed. Cut offs were found to be between 10 and 100 pg/ml, dependent on target expression and target cell line. Importantly, combinations of 2, 3 or 5 AMs, targeting different antigens expressed on the same target cell, cause target- cell lysis at concentrations below the activation threshold for single AMs (exemplified for HL-60 in Figure A) . Our results clearly demonstrate an additive effect in combining different AMs to hurdle the activation threshold. Moreover, in a JeKo 1 CD19 and/or CD20 knock out (KO) antigen-loss model, combinations of AMs targeting CD19, CD20 and ROR1 can differentiate between wild type and antigen -1 (CD19 or CD20 KO) or antigen -2 (CD19 and CD20 KO) variants in medi ating target- cell lysis, even though at least one target antigen is expressed. Finally, we found that combinations of CD10, CD19, CD22 and CD138 sufficiently eliminate Nalm-6 BCP-ALL cells, while sparing healthy B cells in co - culture experiments. Similar results were obtained in co - culture experiments of HL-60 AML cells with monocytes, neutrophils as well as CD34- enriched hematopoietic progenitor cells, applying combinations of CD32, CD33, CD38, CD123, CD305 and CLL1. Co - culturing experiments using autologous blasts, monocytes, neutrophils and aCAR-Ts are ongoing. Together, our results indicate that aCAR-Ts in combination with selected AM combinations might have the ability to identify and specifically eliminate cancer cells based on complex antigen expression profiles. This would have major implications for clinical translation, enabling combinatorial therapy, essential to avoid antigen evasion, and the possibility to spare vitally essential tissue from elimination. Figure. Figure. Disclosures Seitz: Miltenyi Biotec: Patents & Royalties, Research Funding. Mittelstaet:Miltenyi Biotec: Employment, Patents & Royalties. Lock:Miltenyi Biotec: Employment. Kaiser:Miltenyi Biotec: Employment, Patents & Royalties. Handgretinger:Miltenyi Biotec: Patents & Royalties: Co-patent holder of TcR alpha/beta depletion technologies, Research Funding. Lang:Miltenyi Biotec: Patents & Royalties, Research Funding. Schlegel:Miltenyi Biotec: Patents & Royalties, Research Funding.

scholarly journals RhC Phenotyping, Adsorption/Elution Test, and SSP-PCR: The Combined Test for D-Elute Phenotype Screening in Thai RhD-Negative Blood Donors

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Songsak Srijinda ◽  
Chamaiporn Suwanasophon ◽  
Unchalee Visawapoka ◽  
Malinee Pongsavee
Keyword(s):  
Blood Group ◽  
Blood Donors ◽  
Blood Type ◽  
Thai Population ◽  
Indirect Antiglobulin Test ◽  
Phenotype Screening ◽  
Combined Test ◽  
Clinically Significant ◽  
D Antigen ◽  
Asian People

The Rhesus (Rh) blood group is the most polymorphic human blood group and it is clinically significant in transfusion medicine. Especially, D antigen is the most important and highly immunogenic antigen. Due to anti-D, it is the cause of the hemolytic disease of the newborn and transfusion reaction. About 0.1%–0.5% of Asian people are RhD-negative, whereas in the Thai population, the RhD-negative blood type only occurs in 0.3%. Approximately 10%–30% of RhD-negative in Eastern Asian people actually were D-elute (DEL) phenotype, the very weak D antigen that cannot be detected by indirect antiglobulin test (IAT). There are many reports about anti-D immunization in RhD-negative recipients through the transfusion of red blood cells from individuals with DEL phenotype. D-elute phenotype screening in Thai RhD-negative blood donors was studied to distinguish true RhD-negative from DEL phenotype. A total of 254 Thai serologically RhD-negative blood donors were tested for RhCE phenotypes and anti-D adsorption/elution test. In addition, RhC(+) samples were tested for RHD 1227A allele by SSP-PCR technique. The RhD-negative phenotype samples consisted of 131 ccee, 4 ccEe, 1 ccEE, 101 Ccee, 16 CCee, and 1 CcEe. The 42 Ccee and 8 CCee phenotype samples were typed as DEL phenotype and 96% of DEL samples were positive for RHD 1227A allele. The incidence of RhC(+) was 46.4%, and 48 of the 118 RhC(+) samples were positive for both anti-D adsorption/elution test and SSP-PCR technique for RHD 1227A allele. The sensitivity and specificity were 96% and 100%, respectively, for RHD 1227A detection as compared with the adsorption/elution test. In conclusion, RhC(+) phenotype can combine with anti-D adsorption/elution test and RHD 1227A allele SSP-PCR technique for distinguishing true RhD-negative from DEL phenotype.

scholarly journals Next Generation Sequencing for Blood Group Antigen Profiling

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. SCI-24-SCI-24
Author(s):  
William Lane
Keyword(s):  
Blood Group ◽  
Conflicts Of Interest ◽  
Antigen Expression ◽  
Relevant Information ◽  
Hematologic Malignancies ◽  
Start Codon ◽  
Data Sets ◽  
Genetic Changes ◽  
Clinically Significant ◽  
A Minor

Abstract There are over 300 serologically defined red blood cell (RBC) antigens and 33 serologically defined platelet antigens, most of which have known genetic changes in 45 RBC or 6 platelet genes that correlate with antigen expression. Exposure to non-self RBC antigens during transfusion or pregnancy can lead to the development of alloantibodies, which on re-exposure can lead to clinically significant and even fatal complications. Therefore, it is vital to know which antigens are present on RBCs. However, traditional serologic phenotyping methods are labor intensive, costly, sometimes unreliable, and reagents are not always available. As such, routine antigen typing is only done for ABO and D antigens. A large percentage of blood is given for hematologic malignancies that will soon get routine whole genome sequencing (WGS). For a minor added cost this data could be used for RBC antigen prediction. However, there are no published reports of using WGS data to predict RBC antigens. This is likely for several reasons: (1) none of the existing WGS data sets have paired serologic RBC phenotypes, (2) there are no fully annotated and complete databases of genotypes to phenotypes, (3) all of the known alleles are defined using cDNAs numbered relative to the start codon without human genome coordinates, and (4) lack of software capable of automated RBC antigen prediction. We have created a fully interactive web site of all known blood group genotype to phenotype correlations, fully annotated with relevant information, and mapped to and visually overlaid to their corresponding human reference genome gene sequences, with algorithms to predict antigen phenotypes from inputted sequences. These predictions are part of the General Genome Reports for the 100 patients getting WGS as part of The MedSeq Project. In addition, each patient is undergoing an extensive antigen phenotypic workup using traditional blood bank serology and currently available SNP PCR based assays, which are being used to validate and improve our prediction strategies. As clinical WGS becomes pervasive we hope that comprehensive blood group prediction will be done on everyone, allowing for easy identification of rare donors and the prevention of alloantibody formation using extended upfront matching of antigens from sequenced recipients and donor. Disclosures No relevant conflicts of interest to declare.

AB0 Blood Groups and Coronary Heart Disease (CHD)

1980 ◽  
Vol 43 (02) ◽  
pp. 137-140 ◽  
Author(s):  
Jan Erikssen ◽  
Erik Thaulow ◽  
Helge Stormorken ◽  
Ole Brendemoen ◽  
Arvid Hellem
Keyword(s):  
Coronary Artery ◽  
Blood Group ◽  
Artery Bypass ◽  
Laboratory Data ◽  
Epidemiological Data ◽  
Consecutive Series ◽  
Related Factors ◽  
Ab0 Blood Groups ◽  
Clinically Significant ◽  
Artery Disease

SummaryThe view based on epidemiological and laboratory data that blood group A subjects (=A) have clinically significant higher thrombotic potential than blood group 0 subjects (= O), is supported by the present finding of a significantly higher platelet retention in A than 0.The completely normal ABO distribution found among 71 cases of proven latent CHD, and the disproportionate excess of 0 vs. A in a consecutive series of 191 coronary artery bypass candidates apparently conflict with epidemiological data indicating a higher risk of achieving CHD in A than 0. The conflict may be solved by suggestinga) that the »thrombotic proneness« in A compared with 0 causes a poorer prognosis in CHD among the former, leaving a disproportionate excess of 0 among longterm CHD survivors, and b) that AB0-related factors have had an insignificant, independent impact on the evolution of preclinical coronary artery disease in our 71 men with latent CHD.

A Caution in Association of ABO Blood Group with COVID-19

2020 ◽  
Keyword(s):  
Gene Cluster ◽  
Clinical Outcomes ◽  
Blood Group ◽  
Association Analysis ◽  
Blood Type ◽  
Genome Wide Association ◽  
Chromosome 3 ◽  
Abo Blood Group ◽  
Genome Wide Association Analysis ◽  
Genome Wide

A comment on Zhao J, Yang Y, Huang H, Li D, Gu D, Lu X, et al. Association of ABO blood group and Covid19 susceptability. medRxiv [PREPRINT]. 2020; https://doi.org/10.1101/2020.03.11.20031096. Zeng X, Fan H, Lu D, Huang F, Meng X, Li Z, et al. Association between ABO blood group and clinical outcomes of Covid19. medRxiv[PREPRINT].2020; https://doi.org/10.1101/2020.04.15.20063107. Zietz M, Tatonetti N. Testing the association between blood type and COVID-19 infection, intubation, and death medRxiv [PREPRINT]. 2020; https://doi.org/10.1101/2020.04.08.20058073. Ellinghaus D, Degenhardt F, Bujanda L, al. e. The ABO blood group and a chromosome 3 gene cluster associate with SRAS-CoV2 respitarory failure in an Italy-Spain genome-wide association analysis. medRxiv. 2020; https://doi.org/10.1101/2020.05.31.20114991.

SISTEM PAKAR MENU MAKANAN SEHAT BAGI PENDERITA KOLESTEROL DENGAN METODE FORWARD CHAINING

2017 ◽  
Vol 3 (2) ◽  
pp. 72
Author(s):  
Gusnita Darmawati
Keyword(s):  
Expert System ◽  
Cholesterol Level ◽  
Blood Group ◽  
Healthy Food ◽  
Healthy Diet ◽  
Blood Type ◽  
Forward Chaining ◽  
Cholesterol Levels ◽  
Microsoft Office ◽  
Visual Basic 6.0

<p>Penelitian ini membangun suatu sistem pakar untuk menentukan menu makanan sehat berdasarkan golongan darah dan tingkat kadar kolesterol pasien dengan metode Forward Chaining. Tujuan untuk membantu orang awam dalam menentukan menu makanan sehat untuk pasien kolesterol. Sistem ini menganalisa masalah penentuan menu makanan sehat berdasarkan golongan darah dan tingkat kadar kolesterol pasien. Hasil yang diperoleh dari sitem pakar ini adalah berupa informasi makanan sehat yang akan dikonsumsi oleh pasien kolesterol dengan jenis golongan darah dan tingkat kadar kolesterol yang berbeda. Analisa dilakukan dengan cara mengetahui jenis golongan darah dan tingkat kadar kolesterol pasien yang ditampilkan oleh program sistem pakar ini, rancangan sistem ini menggunakan inference forward chaining, dengan implementasi sistem menggunakan sistem database Microsoft Office Access dan bahasa pemrograman Visual Basic 6.0. Dari rancangan aplikasi sistem pakar yang dibuat, maka orang awam yang memderita kolesterol dapat menentukan menu makanan sehat untuk di konsumsi berdasarkan golongan darah dan tingkat kadar kolesterol dengan menjalankan aplikasi sistem pakar.</p><p><em><br /></em></p><p><em><em>This study builds an expert system to determine the healthy food menu based on blood type and cholesterol levels of patients with Forward Chaining method. The goal is to help the layman in determining a healthy diet for cholesterol patients. This system analyzes the problem of determining healthy food menu based on blood group and patient cholesterol level. The results obtained from this expert system is in the form of healthy food information that will be consumed by cholesterol patients with the type of blood group and different cholesterol levels. From the design of expert system applications created, the layman who memderita cholesterol can determine the healthy diet to be consumed by blood type and cholesterol level by running an expert system application.<br /> <br /> </em></em></p>

scholarly journals POS0384 A NOVEL MECHANISM LINKING MUCOSAL BACTERIA WITH AUTOANTIBODY RESPONSES IN RA: ACETYLATED BACTERIAL LYSATE AS A MODEL ANTIGEN

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 422.1-422
Author(s):  
M. Volkov ◽  
A. S. B. Kampstra ◽  
K. van Schie ◽  
J. Kwekkeboom ◽  
T. Huizinga ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Activation ◽  
Positive Control ◽  
Negative Control ◽  
B Cell Activation ◽  
Human Fibrinogen ◽  
Post Translational Modifications ◽  
E Coli ◽  
Bacterial Proteins ◽  
Citrullinated Proteins

Background:Rheumatoid arthritis (RA) is characterized by autoantibodies against post-translationally modified proteins (AMPA) such as citrullinated, carbamylated and acetylated proteins. Importantly, these antibodies are highly multireactive, as they often recognize more than one of these post-translational modifications. Despite extensive research, the antigens inducing the breach of tolerance remain unknown, although microbial antigens are often suspected. Various bacteria are known to be capable of acetylation, therefore, it is intriguing to know what mechanisms can underlie the breach of tolerance towards acetylated proteins and development of anti-acetylated protein antibodies (AAPA).Objectives:To investigate whether acetylated proteins of bacterial origin (1) are recognized by human derived AMPA and AMPA expressing B cells; and (2) can induce AMPA development when used to immunize mice.Methods:Acetylated E. coli proteins were acquired with two separate methods (Figure 1A): by culturing E. coli in a condition promoting auto-acetylation (intrinsically acetylated bacterial proteins, IABP), or by directly acetylating lysate-derived proteins via a chemical reaction (extrinsically acetylated BP, EABP). Acetylated ovalbumin (AcOVA) served as positive control for AAPA induction in mice, non-acetylated BP (NABP) and phosphate buffer saline (PBS) served as negative control. Mice were immunized with these proteins and the resulting antibody response was studied by ELISA. Furthermore, EABP/IABP/NABP were investigated for recognition by human-derived AAPA with ELISA and AAPA-expressing B cells with spleen tyrosine kinase (Syk) phosphorylation assay; acetylated human fibrinogen and native fibrinogen served as positive and negative control.Results:Repetitive immunization of mice with EABP resulted in an AMPA response recognizing acetylated, carbamylated and citrullinated proteins. AMPA titers in these mice exceeded the titers in the positive control mice immunized with AcOVA and were substantially higher than in the NABP-immunized mice (Figure 1B). Human-derived monoclonal AAPA recognized EABP and IABP (not shown). B cell activation (measured by Syk phosphorylation) assay indicated that AAPA expressing B cells recognized EABP and (to a lesser extent) IABP, but not NABP (Figure 1C).Conclusion:Acetylated bacterial proteins are potent antigens that can induce cross-reactive AMPA responses in mice and they are recognized by human AAPA. This suggests that acetylated bacterial proteins could possibly be involved in the breach of tolerance in RA.Acknowledgements:We thank Dr. Can Araman and Prof. Chunaram Choudhary for their advice regarding optimization of bacterial auto-acetylation.Disclosure of Interests:None declared

scholarly journals ABO and P1 Blood Group Antigen Expression andstxGenotype and Outcome of ChildhoodEscherichia coliO157:H7 Infections

2002 ◽  
Vol 185 (2) ◽  
pp. 214-219 ◽  
Author(s):  
Srdjan Jelacic ◽  
Cheryl L. Wobbe ◽  
Daniel R. Boster ◽  
Marcia A. Ciol ◽  
Sandra L. Watkins ◽  
...  
Keyword(s):  
Blood Group ◽  
Antigen Expression ◽  
Blood Group Antigen

ABO histo-blood group antigen expression on the graft endothelium long term after ABO-compatible, non-identical heart transplantation.

2006 ◽  
Vol 13 (2) ◽  
pp. 166-170 ◽  
Author(s):  
Simon C. Koestner ◽  
Andreas Kappeler ◽  
Thomas Schaffner ◽  
Thierry P. Carrel ◽  
Paul J. Mohacsi
Keyword(s):  
Heart Transplantation ◽  
Blood Group ◽  
Antigen Expression ◽  
Blood Group Antigen
Sign in / Sign up

Export Citation Format

Share Document