China
Africa
Explore chapters and articles related to this topic
Fetal and Neonatal Alloimmune Thrombocytopenia
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Human leukocyte antigens (HLA): Human leukocyte antigens (HLA) are proteins located on white blood cells and other tissues including platelets, and alloantibodies can also be made against them. There is a known association between HPA-1a immunization and HLA-DRB3*01:01. Based on recent systematic reviews and meta-analyses:The risk of becoming HPA-1a immunized is 25 times more likely for women who are HLA-DRB3*01:01 positive, compared to HPA-1a negative women expressing this HLA allele [4].The level of anti-HPA-1a antibody is lower in HLA-DRB3*01:01 negative women compared to women who have this allele [14].Neonatal platelet count is higher in children born to HLA-DRB3*01:01 negative mothers [4, 14].The odds of severe fetal/neonatal outcomes are low for HPA-1a-immunized women who are HLA-DRB3*01:01 negative (OR 0.08, 95% CI 0.02–0.37) [4].
Lenalidomide improves the antitumor activity of CAR-T cells directed toward the intracellular Wilms Tumor 1 antigen
Published in Hematology, 2021
Li Zhang, Guangyi Jin, Ziren Chen, Changhua Yu, Yonghui Li, Yisheng Li, Jinghong Chen, Li Yu
We analyzed the proteome of Mock-T and the WT1 CAR-T cells treated with and without LEN. As compared to the Mock-T cells, T cells transduced with the WT1 CAR were found to have highly similar changes in protein expression pattern (Figure 7(A)), indicating that WT1 CAR had little effect on the cells, which is in consistent with our findings in the growth of CAR-T cells. More than 100 proteins were differentially expressed among the LEN-treated and untreated CAR-T cells (Figure 7(B)) (102 progressively upregulated and 14 downregulated). As expected, CAR-T cells treated with LEN showed greater upregulation of protein profiles related to T-cell activation and MHC class I and II molecules expression (Figure 7(C)). The upregulation of the expression of key proteins involved in T-cell activation, such as IL2RA, CD40LG, CD8A and CD6, and the concurrent increase in the expression of the MHC class I and II molecules-associated proteins, such as HLA-B, HLA-F, HLA-DQB1 and HLA-DRB3 (Figure 7(C)). Proteins associated with immune synapse, such as ACTIN1, ACTN3, ACTR5, ANXA1, LGALS3BP, TRIP6 and TRIP10, are up-regulated together with proteins associated with enhanced homing capacities such as ITGB1, TOM1 and MLST8 [11,18]. Moreover, the expression levels of the proteins associated with mitochondrial activity, including TMEM65, FDXR, NDUFS5 and MTCH1, were significantly higher in WT1 CAR-T cells treated with LEN. Thus, our proteomic data showed that LEN is useful to improve the function of CAR-T cells.
Hematopoietic stem cell transplant with HLA-mismatched grafts: impact of donor, source, conditioning, and graft versus host disease prophylaxis
Published in Expert Review of Hematology, 2019
Leland Metheny, Marcos de Lima
According to the National Marrow Donor Program (NMDP), age less than 33 is associated with less GVHD and better OS in unrelated donor transplantation [85,86]. Multi-parity of the donor is associated with increased risk of cGVHD [86]. Similarly to haplo-identical [51] and MUD [86] transplants, preferred MMUD are therefore young males and the preferred source of cells is bone marrow to reduce the risk of GVHD [87]. In regards to HLA-matching, the maximum allowed mismatch should be 1 loci, as each HLA-mismatch is associated with decreased OS of roughly 10% [80]. If there is a mismatch at either HLA-A, B, C, or DRB1, assessment of low expression loci (HLA DRB3/4/5, DQ, and DP) should be performed as there is data to suggest that greater matching at these loci may improve clinical outcomes such as decreased aGVHD rates and improved OS [82]. The standard minimum bone marrow cell dose for MSD and MUD is 3 × 108 TNC/kg [86,88], as a higher cell dose is associated with faster immune recovery and hematologic engraftment. DSA are associated with engraftment failure in allogeneic transplant [89] and if the recipient has DSA against a particular donor, another donor should be chosen if possible, as discussed above. Strategies to treat DSA have been investigated with varying degrees of success [90].
Mepolizumab for the treatment of eosinophilic granulomatosis with polyangiitis
Published in Expert Opinion on Biological Therapy, 2019
Daniel Ennis, Jason Kihyuk Lee, Christian Pagnoux
Multiple genetic and epigenetic risk factors may play a role in EGPA, based on studies of limited sample size. The most consistent relationship is demonstrated with the human leukocyte antigen (HLA) genes encoding the major histocompatibility complex proteins. In a single centre genotyping study of 48 patients with EGPA and 350 healthy controls, HLA-DRB1*07 allele (OR 2.42) and HLA-DRB4 gene (OR 2.49) conferred increased risk for EGPA, whereas the HLA-DRB3 gene was associated with a lower risk (OR 0.54). Furthermore, HLA-DRB4 frequency correlated with the number of vasculitic symptoms and ANCA positivity [57].