Transcriptome analysis of severely active chronic spontaneous urticaria shows an overall immunological skin involvement

Giménez‐Arnau, Ana; Curto‐Barredo, Laia; Nonell, Lara; Puigdecanet, Eulàlia; Yélamos, José; Gimeno, Ramón; Rüberg, Silvia; Santamaria‐Babí, Luis F.

doi:10.1111/all.13183

Cited by 35 publications

(44 citation statements)

References 45 publications

(89 reference statements)

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“…Many studies have shown that disease tissues exhibit molecular heterogeneity (1)(2)(3). In particular, characterization of tumor profiles has been used extensively to subtype cancers (4)(5)(6), with breast cancer being a quintessential example (7).…”

Section: Introductionmentioning

confidence: 99%

Reparameterization of PAM50 expression identifies novel breast tumor dimensions and leads to discovery of a breast cancer susceptibility locus at 12q15

Madsen

Knight

Sweeney

et al. 2017

Preprint

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Conflict of Interest StatementPhil Bernard is an inventor of the PAM50 gene expression signature and a stakeholder in BioClassifier LLC, a company that licensed the PAM50 know-how to Nanostring Inc for the commercialization of Prosigna.peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/133397 doi: bioRxiv preprint first posted online May. 9, 2017; 2 AbstractIt is well-known that breast tumors exhibit different expression patterns that can be used to assign intrinsic subtypes -the PAM50 assay, for example, categorizes tumors into: Luminal A, Luminal B, HER2-enriched and Basal-like -yet tumors are often more complex than categorization can describe. We used 911 sporadic breast tumors to reparameterize expression from the PAM50 genes to five orthogonal tumor dimensions using principal components (PC). Three dimensions captured intrinsic subtype, two dimensions were novel, and all replicated in 945 TCGA tumors. By definition dimensions are independent, an important attribute for inclusion in downstream studies exploring effects of tumor diversity. One application where tumor subtyping has failed to provide impact is susceptibility genetics. Germline genetic heterogeneity reduces power for gene-finding. The identification of heritable tumor characteristics has potential to increase homogeneity. We compared 238 breast tumors from high-risk pedigrees not attributable to BRCA1 or BRCA2 to 911 sporadic breast tumors. Two PC dimensions were significantly enriched in the pedigrees (intrinsic subtypes were not). We performed proof-of-concept gene-mapping in one enriched pedigree and identified a 0.5 Mb genomewide significant region at 12q15 that segregated to the 8 breast cancer cases with the most extreme PC tumors through 32 meioses (p=2.6×10 -8 ).In conclusion, our study: suggests a new approach to describe tumor diversity; supports the hypothesis that tumor characteristics are heritable providing new avenues for germline studies; and proposes a new breast cancer locus. Reparameterization of expression patterns may similarly inform other studies attempting to model the effects of tumor heterogeneity.

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Section: Introductionmentioning

confidence: 99%

Reparameterization of PAM50 expression identifies novel breast tumor dimensions and leads to discovery of a breast cancer susceptibility locus at 12q15

Madsen

Knight

Sweeney

et al. 2017

Preprint

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“…An increasing number of researchers have begun to focus on the application of high-throughput sequencing to explore the pathogenesis of complex genetic skin diseases, including psoriasis, atopic dermatitis, and systemic lupus erythematosus, at the transcriptional levels with differentially expressed genes, and even transcription factors (Flint et al, 2015; Suarez-Farinas et al, 2015; Swindell et al, 2014). Only a few studies have examined mRNA expression in CSU (Gimenez-Arnau et al, 2017; Patel et al, 2015). Researchers have observed that lesion skins expressed higher levels of inflammation-related genes than non-lesions.…”

Section: Discussionmentioning

confidence: 99%

“…Researchers have observed that lesion skins expressed higher levels of inflammation-related genes than non-lesions. A recent study on CSU using a microarray also showed imbalanced immunological skin conditions with differential gene expression between lesions and non-lesions (Gimenez-Arnau et al, 2017). However, the underlying mechanism of the effect of BCG-PSN pretreatment on mast cells remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of Bacillus Calmette–Guerin polysaccharide nucleic acid on mast cell at the transcriptional level

Yan

Mao

et al. 2019

PeerJ

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Background Chronic spontaneous urticaria (CSU) is a common and recurrent autoimmune-related disease with unclear pathogenesis. Dysfunction of immune cells, such as T cells, mast cells, and basophils, is involved. Bacillus Calmette–Guerin polysaccharide nucleic acid (BCG–PSN), an immunomodulator partially extracted from BCG, can be used in the combined treatment of CSU with an unknown mechanism. Methods To study the therapeutic effect and mechanism of BCG–PSN on CSU, we initially assessed the clinical efficacy in 110 enrolled CSU patients of 4-week antihistamine monotherapy vs. antihistamine plus BCG–PSN combined therapy. Subsequently, to explore the further mechanism of BCG-PSN, the mast cell line RBL-2H3 pretreated with BCG-PSN was used to evaluate the transcriptional expression profiles via lncRNA sequencing. Real time PCR was conducted to validate the candidate gene expression. Results We found no significant difference in treatment efficacy between the BCG–PSN group (71.7%) and the monotherapy group (71.9%). However, the average time of complete relief in the BCG–PSN group was significantly shorter than that in the monotherapy group (36.77 ± 17.33 vs. 51.27 ± 16.80, p = 0.026). In vitro experiments showed that BCG-PSN inhibited β-hexosaminidase release rates in IgE-sensitized RBL-2H3 cells (p < 0.001). Sequencing data revealed the expression profiles of functional genes, including a significant decrease in Erb-B2 receptor tyrosine kinase 4, which can be regulated by the nuclear factor kappa B (NF-κB) pathway. Discussion CSU is a chronic, recurrent disease with complex pathogenesis. Mast cells and basophils are the primary target cells of the disease. BCG–PSN decrease the β-HEX release rates and regulated IgE-mediated mast cell activation in RBL-2H3 cells by mediating immune-related gene expression including ERBB4. These findings suggest that BCG–PSN may mediate ERBB4 expression via the NF-κB pathway and may have value in the treatment of CSU.

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“…These results corroborate published microarray reports. 7,8 In addition, a posi- HCs, IL6 P = 0.02; IL1β P = 0.0003 ) (Figure 2 A,B), and expression of IL6 and IL1β mRNA was positively correlated ( P < 0.0001) ( Figure S1 ).…”

Section: Il-6 and Il-1β Expression Is Increased In Autologous Serum Smentioning

confidence: 90%

IL‐6 and IL‐1β expression is increased in autologous serum skin test of patients with chronic spontaneous urticaria

Montjoye

Choteau

Herman

et al. 2019

Allergy

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Transcriptome analysis of severely active chronic spontaneous urticaria shows an overall immunological skin involvement

Abstract: The skin of CSU patients with a severely active disease shows an overall immunological skin involvement showing a peculiar gene profile.

Cited by 35 publications

References 45 publications

Reparameterization of PAM50 expression identifies novel breast tumor dimensions and leads to discovery of a breast cancer susceptibility locus at 12q15

Reparameterization of PAM50 expression identifies novel breast tumor dimensions and leads to discovery of a breast cancer susceptibility locus at 12q15

Therapeutic effect of Bacillus Calmette–Guerin polysaccharide nucleic acid on mast cell at the transcriptional level

IL‐6 and IL‐1β expression is increased in autologous serum skin test of patients with chronic spontaneous urticaria

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