Project description:Wild-type KATOIII cells and their derived mutant clones B3 and B4 harboring biallelic deletions of the +22.6-kb site, located 22.6 kb downstream from the ABO translation start site
Project description:Background: Plasmapheresis/rituximab-based desensitization therapy has successfully reduced anti-ABO antibody levels and suppressed antibody-mediated rejection (AMR) in ABO-incompatible (ABOi) kidney transplantation (KT). However, high titers of anti-ABO antibodies in some patients are refractory to standard desensitization, leading to loss of KT opportunities or AMR. Methods: Eculizumab-based desensitization was used to rescue high-titer ABOi KT patients refractory to plasmapheresis/rituximab-based desensitization. Results: The initial titers of anti-ABO IgG antibodies in the two patients were 1:512 and >1:1024; the final pre-transplant titers after desensitization were 1:128 and 1:64. Both patients received eculizumab from the day of KT to two or four weeks post-KT and maintained stable renal function up to one-year post-transplantation without overt infectious complications, despite early episodes of suspicious AMR or borderline T cell-mediated rejection. Molecular phenotype analysis of allograft biopsies using the Banff Human Organ Transplant gene panel revealed that gene expression patterns in the ABOi KT with eculizumab group overlapped with those in the ABOi KT with AMR group more than in the ABOi KT without AMR group, except for complement pathway-related gene expression. Anti-ABO antibody titers decreased to low levels 1–3 months post-transplant in the eculizumab group in parallel with decreasing anti-B-specific B cells at this time point. Conclusions: Short-term eculizumab-based desensitization therapy is promising for rescuing ABOi KT recipients with unacceptably high anti-ABO antibody titers refractory to plasmapheresis-based desensitization therapy.
Project description:Purpose: This study uses a high-throughput glycan microarray to develop a novel method to assign ABO blood type. The method will then be applied to samples from patients treated with PROSTVAC to determine if blood type correlates with survival Results: Many blood group A and B antigens correlate with blood type. Blood typing is best achieved using a combination of 10 signals Conclusion: ABO blood type can be determined with greater than 97% accuracy using only 4 microliters of serum.
Project description:Purpose: This study uses a high-throughput glycan microarray to assign ABO blood type to patients from a clinical trial on PROSTVAC. The goal is to determine if blood type correlates with survival for patients treated with PROSTVAC Results: Blood types were assigned and type B and O patients were found to have longer survival than type A and AB patients Conclusion: Blood type may serve as a convenient method to identify patients likely to respond favorably to PROSTVAC therapy
2016-04-28 | GSE68404 | GEO
Project description:A novel splice site mutation in IDUA genen
Project description:Regular blood transfusion is the cornerstone of care for patients with red blood cell (RBC) disorders such as thalassemia or sickle cell disease. With repeated transfusion, alloimmunisation often occurs due to incompatibility at the level of minor blood group antigens. We use CRISPR-mediated genome editing of an immortalised human erythroblast cell line (BEL-A) to generate multiple enucleation competent cell lines deficient in individual blood groups. Edits are combined to generate a single cell line deficient in multiple antigens responsible for the most common transfusion incompatibilities: ABO (Bombay phenotype), Rh (Rhnull), Kell (K0), Duffy (Duffynull), GPB (S- s- U-). These cells can be differentiated to generate deformable reticulocytes, illustrating the capacity for coexistence of multiple rare blood group antigen null phenotypes. This study provides the first proof-of-principle demonstration of combinatorial CRISPR-mediated blood group gene editing to generate customisable or multi-compatible RBCs for diagnostic reagents or recipients with complicated matching requirements.
Project description:A knockin mouse line created that contains a point mutation that elminates the requisite GT in the 5' donor site of each of the NCoRω splice variants, thus preventing splicing at that site and forcing splicing of the reciprocal NcoRδ splice variant.
