FCERI and Histamine Metabolism Gene Variability in Selective Responders to NSAIDS

Amo, Gemma; Cornejo-García, J.A.; García-Menaya, Jesús Miguel; Cordobés, Concepción; Torres, Marı́a José; Esguevillas, Gara; Mayorga, Cristobalina; Martı́nez, Carmen; Blanca‐López, Natalia; Cantó, Gabriela; Ramos, Alfonso; Blanca, Miguel; Agúndez, José A. G.; García‐Martín, Elena

doi:10.3389/fphar.2016.00353

Cited by 23 publications

(13 citation statements)

References 53 publications

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“…On the other hand, several genes were found to be significantly upregulated in T cells from tolerized kidneys, an example being the IgE receptor–related gene Fcer1g ( Supplemental Figure 4B ). This gene has previously been implicated in asthma and allergic reactions ( 36 , 37 ); however, its role in T cell immune tolerance in transplantation remains unknown.…”

Section: Resultsmentioning

confidence: 99%

Single cell transcriptomics of mouse kidney transplants reveals a myeloid cell pathway for transplant rejection

Dangi¹,

Natesh²,

Husain³

et al. 2020

JCI Insight

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Myeloid cells are increasingly recognized as major players in transplant rejection. Here, we used a murine kidney transplantation model and single cell transcriptomics to dissect the contribution of myeloid cell subsets and their potential signaling pathways to kidney transplant rejection. Using a variety of bioinformatic techniques, including machine learning, we demonstrate that kidney allograft–infiltrating myeloid cells followed a trajectory of differentiation from monocytes to proinflammatory macrophages, and they exhibited distinct interactions with kidney allograft parenchymal cells. While this process correlated with a unique pattern of myeloid cell transcripts, a top gene identified was Axl , a member of the receptor tyrosine kinase family Tyro3/Axl/Mertk (TAM). Using kidney transplant recipients with Axl gene deficiency, we further demonstrate that Axl augmented intragraft differentiation of proinflammatory macrophages, likely via its effect on the transcription factor Cebpb. This, in turn, promoted intragraft recruitment, differentiation, and proliferation of donor-specific T cells, and it enhanced early allograft inflammation evidenced by histology. We conclude that myeloid cell Axl expression identified by single cell transcriptomics of kidney allografts in our study plays a major role in promoting intragraft myeloid cell and T cell differentiation, and it presents a potentially novel therapeutic target for controlling kidney allograft rejection and improving kidney allograft survival.

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Section: Resultsmentioning

confidence: 99%

Single cell transcriptomics of mouse kidney transplants reveals a myeloid cell pathway for transplant rejection

Dangi¹,

Natesh²,

Husain³

et al. 2020

JCI Insight

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“…The concentration of histamine depends on the expression and activity of histamine receptors [ 36 ]. Histamine metabolism is closely related to food allergy [ 37 ]. Deoxycholic acid and lithocholic acid play a conductive role in maintaining the homeostasis of the bile secretion pathway.…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus rhamnosus GG Reduces β-conglycinin-Allergy-Induced Apoptotic Cells by Regulating Bacteroides and Bile Secretion Pathway in Intestinal Contents of BALB/c Mice

Chen

et al. 2020

Nutrients

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Allergy can cause intestinal damage, including through cell apoptosis. In this study, intestinal cell apoptosis was first observed in the β-conglycinin (β-CG) allergy model, and the effect of Lactobacillus rhamnosus GG (LGG) on reducing apoptosis of cells in the intestine and its underlying mechanisms were further investigated. Allergic mice received oral LGG daily, and intestinal tissue apoptotic cells, gut microbiota, and metabolites were evaluated six and nine days after intervention. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analysis revealed that LGG intervention could reduce the incidence of cell apoptosis more effectively than natural recovery (NR). The results of 16S rRNA analysis indicated that LGG intervention led to an increase in the relative abundance of Bacteroides. Metabolite analysis of intestinal contents indicated that histamine, N-acetylhistamine, N(α)-γ-glutamylhistamine, phenylalanine, tryptophan, arachidonic acid malate, and xanthine were significantly decreased, and deoxycholic acid, lithocholic acid were significantly increased after the LGG intervention on β-CG allergy; the decreases in histamine and N(α)-γ-glutamylhistamine were significant compared with those of NR. In conclusion, LGG reduces apoptosis of cells induced by β-CG allergy, which may be related to regulation of Bacteroides and the bile secretion pathway.

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“…The rationale for the selection of the 16 genes included in this study is based on putative mechanisms involved this type of reactions. FCERI plays an essential role in IgE-mediated mechanisms and variants in FCERI genes have been previously described as genetic factors related to asthma (Cui et al, 2003; Kim et al, 2006; Palikhe et al, 2008; Joubert et al, 2011; Ramphul et al, 2014; Yang et al, 2014), allergy (Hasegawa et al, 2003; de Guia et al, 2015; Liao et al, 2015; Amo et al, 2016a,b), and food sensitization (Liu et al, 2011; Hong and Wang, 2012). It has been also described that some variants in genes involved in the vitamin D pathway are related with asthma (Poon et al, 2004; Raby et al, 2004; Wjst, 2005; Wjst et al, 2006; Bossé et al, 2009; Saadi et al, 2009; Li et al, 2011; Pillai et al, 2011; Maalmi et al, 2013; Leung et al, 2015; Hutchinson et al, 2017), especially variations in genes regulated by vitamin D, such as IL4 and its receptor (Burchard et al, 1999; Donfack et al, 2005; Ober and Hoffjan, 2006; Battle et al, 2007; Michel et al, 2010; Baye et al, 2011; Hesselmar et al, 2012; Liu et al, 2012; Micheal et al, 2013; Nie et al, 2013; Zhu et al, 2013; Al-Muhsen et al, 2014; Berenguer et al, 2014; Klaassen et al, 2015; Zhang et al, 2015; Narozna et al, 2016) and IL13 (Black et al, 2009; Bottema et al, 2010; Palikhe et al, 2010; Cui et al, 2012; Accordini et al, 2016; Xu et al, 2017), which are also related to IgE (Marsh et al, 1994; Kabesch et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…It is important to note that the major findings obtained in the present study are novel, since only one of the three SNPs that remained after the multinomial analysis have been previously related with atopy or drug hypersensitivity. Among these, one of the FCER1G SNPs is novel and hence have not been studied before, and the other one has been related with food sensitization (Liu et al, 2011) and has been previously studied in patients with selective hypersensitivity to NSAIDs and allergic rhinitis without significant association (Amo et al, 2016a,b). After the NGS and combined dataset analyses phases, prediction models revealed that one of these SNPs, designated as FCER1G rs36233990 was correct in all models and it allowed an excellent prediction for patients with DHR, IgE-mediated DHR and all IgE-mediated diseases analyzed.…”

Section: Discussionmentioning

confidence: 99%

“…As a matter of fact, several studies demonstrated an association between different allergic diseases, including DHRs, and polymorphisms in these genes (Poon et al, 2004; Raby et al, 2004; Donfack et al, 2005; Bossé et al, 2009; Saadi et al, 2009; Pillai et al, 2011; Micheal et al, 2013; Berenguer et al, 2014; Amo et al, 2016a; Narozna et al, 2016). Several studies addressed the putative impact of exonic and intronic SNPs within the above-mentioned genes and the risk of allergic diseases and/or DHR (Wjst, 2005; Wjst et al, 2006; Battle et al, 2007; Arshad et al, 2008; Sadeghnejad et al, 2008; Weidinger et al, 2008; Black et al, 2009; Bossé et al, 2009; Ferreira et al, 2009; Knutsen et al, 2010; Li et al, 2010, 2012, 2014, 2016; Michel et al, 2010; Moffatt et al, 2010; Cooper et al, 2011; Joubert et al, 2011; Liu et al, 2011; Lu et al, 2011; Park et al, 2011; Paternoster et al, 2011; Pillai et al, 2011; Burkhardt et al, 2012; Choi et al, 2012; Granada et al, 2012; Lasky-Su et al, 2012; Ramasamy et al, 2012; Robinson et al, 2012; Zhou et al, 2012; Anderson et al, 2013; Hur et al, 2013; Ismail et al, 2013; Movahedi et al, 2013; Potaczek et al, 2013; Sharma et al, 2014; Yang et al, 2014; Kumar et al, 2015; Papadopoulou et al, 2015; Pino-Yanes et al, 2015; Tian et al, 2015; Amo et al, 2016a,b; Han et al, 2016; Karaca et al, 2016; Narozna et al, 2016; Overton et al, 2016; Ådjers et al, 2017; Ashley et al, 2017; Park and Tantisira, 2017; Sun et al, 2017; Xu et al, 2017; Zhang et al, 2017; Zhao et al, 2017). However, there is little information about SNPs located in the promoters of these genes, which might have functional consequences.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Novel Biomarkers for Drug Hypersensitivity After Sequencing of the Promoter Area in 16 Genes of the Vitamin D Pathway and the High-Affinity IgE Receptor

et al. 2019

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The prevalence of allergic diseases and drug hypersensitivity reactions (DHRs) during recent years is increasing. Both, allergic diseases and DHRs seem to be related to an interplay between environmental factors and genetic susceptibility. In recent years, a large effort in the elucidation of the genetic mechanisms involved in these disorders has been made, mostly based on case-control studies, and typically focusing on isolated SNPs. These studies provide a limited amount of information, which now can be greatly expanded by the complete coverage that Next Generation Sequencing techniques offer. In this study, we analyzed the promoters of sixteen genes related to the Vitamin D pathway and the high-affinity IgE receptor, including FCER1A, MS4A2, FCER1G, VDR, GC, CYP2R1, CYP27A1, CYP27B1, CYP24A1, RXRA, RXRB, RXRG, IL4, IL4R, IL13 , and IL13RA1 . The study group was composed of patients with allergic rhinitis plus asthma (AR+A), patients with hypersensitivity to beta-lactams (BLs), to NSAIDs including selective hypersensitivity (SH) and cross-reactivity (CR), and healthy controls without antecedents of atopy or adverse drug reactions. We identified 148 gene variations, 43 of which were novel. Multinomial analyses revealed that three SNPs corresponding to the genes FCER1G (rs36233990 and rs2070901), and GC (rs3733359), displayed significant associations and, therefore, were selected for a combined dataset study in a cohort of 2,476 individuals. The strongest association was found with the promoter FCER1G rs36233990 SNP that alters a transcription factor binding site. This SNP was over-represented among AR+A patients and among patients with IgE-mediated diseases, as compared with control individuals or with the rest of patients in this study. Classification models based on the above-mentioned SNPs were able to predict correct clinical group allocations in patients with DHRs, and patients with IgE-mediated DHRs. Our findings reveal gene promoter SNPs that are significant predictors of drug hypersensitivity, thus reinforcing the hypothesis of a genetic predisposition for these diseases.

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FCERI and Histamine Metabolism Gene Variability in Selective Responders to NSAIDS

Cited by 23 publications

References 53 publications

Single cell transcriptomics of mouse kidney transplants reveals a myeloid cell pathway for transplant rejection

Single cell transcriptomics of mouse kidney transplants reveals a myeloid cell pathway for transplant rejection

Lactobacillus rhamnosus GG Reduces β-conglycinin-Allergy-Induced Apoptotic Cells by Regulating Bacteroides and Bile Secretion Pathway in Intestinal Contents of BALB/c Mice

Identification of Novel Biomarkers for Drug Hypersensitivity After Sequencing of the Promoter Area in 16 Genes of the Vitamin D Pathway and the High-Affinity IgE Receptor

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