A common TCN1 loss-of-function variant is associated with lower vitamin B12 concentration in African Americans

Hu, Yao; Raffield, Laura M.; Polfus, Linda M.; Moscati, Arden; Nadkarni, Girish N.; Preuss, Michael; Zhong, Xue; Wei, Qiang; Rich, Stephen S.; Li, Yun; Wilson, James G.; Correa, Adolfo; Loos, Ruth J.F.; Li, Bingshan; Auer, Paul L.; Reiner, Alex P.

doi:10.1182/blood-2018-03-841023

Cited by 8 publications

(7 citation statements)

References 26 publications

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“…The inability to expand NK cells from G-CSF mobilized apheresis that we observed could be somehow expected, as the negative impact of G-CSF on NK cells mobilization and cytotoxicity has been previously reported [ 39 , 40 ]. In the future, if mobilization of progenitor hematopoietic cells is needed, we could consider the use of plerixafor, as it has been proved to effectively mobilize NK cells to the peripheral blood [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Optimizing the Procedure to Manufacture Clinical-Grade NK Cells for Adoptive Immunotherapy

Fernández

Navarro-Zapata

Escudero

et al. 2021

Cancers

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Natural killer (NK) cells represent promising tools for cancer immunotherapy. We report the optimization of an NK cell activation–expansion process and its validation on clinical-scale. Methods: RPMI-1640, stem cell growth medium (SCGM), NK MACS and TexMACS were used as culture mediums. Activated and expanded NK cells (NKAE) were obtained by coculturing total peripheral blood mononuclear cells (PBMC) or CD45RA+ cells with irradiated K562mbIL15-41BBL or K562mbIL21-41BBL. Fold increase, NK cell purity, activation status, cytotoxicity and transcriptome profile were analyzed. Clinical-grade NKAE cells were manufactured in CliniMACS Prodigy. Results: NK MACS and TexMACs achieved the highest NK cell purity and lowest T cell contamination. Obtaining NKAE cells from CD45RA+ cells was feasible although PBMC yielded higher total cell numbers and NK cell purity than CD45RA+ cells. The highest fold expansion and NK purity were achieved by using PBMC and K562mbIL21-41BBL cells. However, no differences in activation and cytotoxicity were found when using either NK cell source or activating cell line. Transcriptome profile showed to be different between basal NK cells and NKAE cells expanded with K562mbIL21-41BBL or K562mbIL15-41BBL. Clinical-grade manufactured NKAE cells complied with the specifications from the Spanish Regulatory Agency. Conclusions: GMP-grade NK cells for clinical use can be obtained by using different starting cells and aAPC.

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Section: Discussionmentioning

confidence: 99%

Optimizing the Procedure to Manufacture Clinical-Grade NK Cells for Adoptive Immunotherapy

Fernández

Navarro-Zapata

Escudero

et al. 2021

Cancers

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“…Polymorphisms in genes related to B12 uptake have also been correlated with decreased serum B12 [66][67][68]. Similarly, polymorphisms in folate uptake genes can cause a folate deficiency [69,70].…”

Section: Causes Of Deficiencymentioning

confidence: 99%

B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease

et al. 2020

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Vitamins B9 (folate) and B12 are essential water-soluble vitamins that play a crucial role in the maintenance of one-carbon metabolism: a set of interconnected biochemical pathways driven by folate and methionine to generate methyl groups for use in DNA synthesis, amino acid homeostasis, antioxidant generation, and epigenetic regulation. Dietary deficiencies in B9 and B12, or genetic polymorphisms that influence the activity of enzymes involved in the folate or methionine cycles, are known to cause developmental defects, impair cognitive function, or block normal blood production. Nutritional deficiencies have historically been treated with dietary supplementation or high-dose parenteral administration that can reverse symptoms in the majority of cases. Elevated levels of these vitamins have more recently been shown to correlate with immune dysfunction, cancer, and increased mortality. Therapies that specifically target one-carbon metabolism are therefore currently being explored for the treatment of immune disorders and cancer. In this review, we will highlight recent studies aimed at elucidating the role of folate, B12, and methionine in one-carbon metabolism during normal cellular processes and in the context of disease progression.

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“…Many whole exome or whole genome sequencing association studies, such as the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine Program (NHLBI TOPMed) and the National Human Genome Research Institute Genome Sequencing Program (NHGRI GSP), seek to identify genes and variants that influence human complex diseases and traits [ 1 – 3 ]. The majority of genetic variants in the human genome are rare [ 4 ], and variants in protein-coding regions have even lower minor allele frequencies (MAFs) [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

PSCAN: Spatial scan tests guided by protein structures improve complex disease gene discovery and signal variant detection

et al. 2020

Self Cite

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Germline disease-causing variants are generally more spatially clustered in protein 3-dimensional structures than benign variants. Motivated by this tendency, we develop a fast and powerful protein-structure-based scan (PSCAN) approach for evaluating gene-level associations with complex disease and detecting signal variants. We validate PSCAN’s performance on synthetic data and two real data sets for lipid traits and Alzheimer’s disease. Our results demonstrate that PSCAN performs competitively with existing gene-level tests while increasing power and identifying more specific signal variant sets. Furthermore, PSCAN enables generation of hypotheses about the molecular basis for the associations in the context of protein structures and functional domains.

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A common TCN1 loss-of-function variant is associated with lower vitamin B12 concentration in African Americans

Abstract: Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas.

Cited by 8 publications

References 26 publications

Optimizing the Procedure to Manufacture Clinical-Grade NK Cells for Adoptive Immunotherapy

Optimizing the Procedure to Manufacture Clinical-Grade NK Cells for Adoptive Immunotherapy

B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease

PSCAN: Spatial scan tests guided by protein structures improve complex disease gene discovery and signal variant detection

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