A calculated panel reactive antibody (cPRA) estimates the percentage of donors with unacceptable antigens (UA) for a recipient. cPRA may be underestimated in transplant candidates with UA to DQA, DPA, and DPB if these are not included in the calculation program. To serve the National Canadian Transplant Programs, a cPRA calculator was developed with complete molecular typing for all donors at HLA-A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPA1, and DPB1, all resolved to serologic equivalents. The prevalence of UA at DQA, DPA and DPB was evaluated in a sensitized regional population. The impact of adding these additional UA to cPRA was calculated alone and in combination, and compared to the baseline cPRA for UA at A, B, C, DR, DR51/52/53, and DQ. Of 740 sensitized transplant candidates, 18% of total and 32% with cPRA≥95% had DQA UA. Twenty-seven percent of total and 54% with cPRA≥95% had DPB UA. Of 280/740 subjects with these UA, 36/280 (13%) had cPRA increase of >20% when they were included, 7% increased cPRA to ≥80% and 6% to ≥95%. Inclusion of DQA, DPA, and DPB UA in Canadian cPRA calculations improves the accuracy of cPRA where these are relevant in allocation.
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http://dx.doi.org/10.1111/ajt.13355 | DOI Listing |
Sci Rep
October 2020
MOGAM Institute for Biomedical Research, 93, 30beon-gil, Ihyeon-ro, Giheung-gu, Yongin-si, Gyeonggi-do, 16924, South Korea.
As recent advancements in the chimeric antigen receptor-T cells have revolutionized the way blood cancers are handled, potential benefits from producing off-the-shelf, standardized immune cells entail the need for development of allogeneic immune cell therapy. However, host rejection driven by HLA disparity in adoptively transferred allogeneic T cells remains a key obstacle to the universal donor T cell therapy. To evade donor HLA-mediated immune rejection, we attempted to eliminate T cell's HLA through the CRISPR/Cas9 gene editing system.
View Article and Find Full Text PDFImmunogenetics
September 2019
Department of Biology, Bates College, 44 Campus Ave, Lewiston, ME, 04240, USA.
The major histocompatibility complex (MHC) is critical to host-pathogen interactions. Class II MHC is a heterodimer, with α and β subunits encoded by different genes. The peptide-binding groove is formed by the first domain of both subunits (α and β), but studies of class II variation or natural selection focus primarily on the β subunit and II B genes.
View Article and Find Full Text PDFJ Med Primatol
December 2018
Caribbean Primate Research Center, University of Puerto Rico-Medical Sciences Campus, San Juan, Puerto Rico.
Background: Knowledge of major histocompatibility complex (MHC) composition and distribution in rhesus macaque colonies is critical for management strategies that maximize the utility of this model for biomedical research.
Methods: Variation within the Mamu-A and Mamu-B (class I) and DRB, DQA/B, and DPA/B (class II) regions of 379 animals from the Caribbean Primate Research Center's (CPRC) specific pathogen free (SPF) colony was examined using massively parallel sequencing.
Results: Analyses of the 7 MHC loci revealed a background of Indian origin with high levels of variation despite past genetic bottlenecks.
Infect Genet Evol
December 2017
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Electronic address:
The northern pig-tailed macaque (Macaca leonina) has been identified as an independent species from the pig-tailed macaque group. The species is a promising animal model for HIV/AIDS pathogenesis and vaccine studies due to susceptibility to HIV-1. However, the major histocompatibility complex (MHC) genetics in northern pig-tailed macaques remains poorly understood.
View Article and Find Full Text PDFBMC Genomics
March 2016
University Program in Ecology, Duke University, Durham, NC, USA.
Background: Across species, diversity at the Major Histocompatibility Complex (MHC) is critical to disease resistance and population health; however, use of MHC diversity to quantify the genetic health of populations has been hampered by the extreme variation found in MHC genes. Next generation sequencing (NGS) technology generates sufficient data to genotype even the most diverse species, but workflows for distinguishing artifacts from alleles are still under development. We used NGS to evaluate the MHC diversity of over 300 captive and wild ring-tailed lemurs (Lemur catta: Primates: Mammalia).
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