Prédisposition aux pathologies auto-immmunes

Dragin, Nadine; Panse, Rozen Le; Berrih‐Aknin, Sonia

doi:10.1051/medsci/20173302012

Cited by 9 publications

(5 citation statements)

References 41 publications

(45 reference statements)

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“…Second, high-diversity, highly abundant BCR repertoire is not restricted to SKCM that bear high somatic mutation burden, suggesting that B cells can infiltrate melanoma in response to other antigens, such as melanoma differentiation and cancer testis antigens [17], viral antigens, and/or potentially other factors such as B cell chemotactic cytokines. This idea is further supported by the previous finding that women with SKCM have significantly lower somatic mutation burden than men [41] and our finding in this study that SKCM in women, who are known to have relatively decreased global central immune (i.e., thymic) tolerance and therefore more prone to autoimmune diseases [42], had a more diverse B cell infiltrate. Third, a substantial non-regulatory B cell presence is likely beneficial for response to anti-CTLA4 inhibitors.…”

Section: Discussionsupporting

confidence: 89%

Prognostic value of B cells in cutaneous melanoma

et al. 2019

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Background Measures of the adaptive immune response have prognostic and predictive associations in melanoma and other cancer types. Specifically, intratumoral T cell density and function have considerable prognostic and predictive value in skin cutaneous melanoma (SKCM). Less is known about the significance of tumor-infiltrating B cells in SKCM. Our goal was to understand the prognostic and predictive value of B cell phenotypic subsets in SKCM using RNA sequencing. Methods We used our previously published algorithm, V’DJer, to assemble B cell receptor (BCR) repertoires and estimate diversity from short-read RNA sequencing (RNA-seq). We applied machine learning-based cellular phenotype classifiers to measure relative similarity of bulk tumor sample gene expression profiles and different B cell phenotypes. We assessed these aspects of B cell biology in 473 SKCM from the Cancer Genome Atlas Project (TCGA) as well as in RNA-seq data corresponding to tumor samples procured from patients who received CTLA-4 and PD-1 inhibitors for metastatic SKCM. Results We found that the BCR repertoire was associated with different clinical factors, such as tumor tissue site and sex. However, increased clonality of the BCR repertoire was favorably prognostic in SKCM and was prognostic even after first conditioning on various clinical factors. Mutation burden was not correlated with any BCR measurement, and no specific mutation had an altered BCR repertoire. Lack of an assembled BCR in pre-treatment tumor tissues was associated with a lack of anti-tumor response to a CTLA-4 inhibitor in metastatic SKCM. Conclusions These findings suggest an important prognostic and predictive role for B cell characteristics in SKCM. This has implications for melanoma immunobiology and potential development of immunogenomics features to predict survival and response to immunotherapy. Electronic supplementary material The online version of this article (10.1186/s13073-019-0647-5) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 89%

Prognostic value of B cells in cutaneous melanoma

et al. 2019

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“…This is consistent with health information seeking literature, where women generally seek medicines information more often than males (35,36). The majority of patients were also female which reflects the general nature of autoimmune diseases treated by DMARDs (37). There were more calls from the patients themselves regarding DMARDs than in ROC, which potentially reflects ownership of their condition and higher involvement in management, a trait consistent across many chronic diseases such as RA (38,39).…”

Section: Discussionsupporting

confidence: 82%

Real-world questions and concerns about disease-modifying antirheumatic drugs (DMARDs): a retrospective analysis of questions to a medicine call center

Masri

Hollingworth

Driel

et al. 2020

Preprint

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Background Disease modifying antirheumatic drugs (DMARDs) have transformed the treatment of numerous autoimmune and inflammatory diseases but their perceived risk of harm be a barrier to use.Methods In a retrospective mixed-methods study, we analysed conventional (c) and biologic (b) DMARDs-related calls and compared them with rest of calls (ROC) from consumers to an Australian national medicine call center operated by clinical pharmacists from September 2002 to June 2010. This includes the period where bDMARDs became available on the Pharmaceutical Benefits Scheme, the government-subsidized prescription medicines formulary. We compared caller and patient demographics, enquiry types and motivation to information-seek for both cDMARDs and bDMARDs with ROC, using a t-test for continuous data and a chi-square test for categorical data. We explored call narratives to identify common themes.Results There were 1,547 calls involving at least one DMARD. The top three cDMARD enquiry types were side effects (27.2%), interactions (21.9%), and risk versus benefit (11.7%). For bDMARDs, the most common queries involved availability and subsidized access (18%), mechanism and profile (15.8%), and side effects (15.1%). The main consumer motivations to information-seek were largely independent of medicines type and included: inadequate information (44%), wanting a second opinion (23.6%), concern about a worrying symptom (18.8%), conflicting information (6.9%), or information overload (2.3%). Question themes common to conventional and biological DMARDs were caller overemphasis on medication risk and the need for reassurance. Callers seeking information about bDMARDs generally overestimated effectiveness and focused their attention on availability, cost, storage, and medicine handling.Conclusion Consumers have considerable uncertainty regarding DMARDs and may overemphasise risk. Patients cautiously assess the benefits and risks of their DMARDs but when new treatments emerge, they tend to overestimate their effectiveness.

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“…Previous studies have reported that sexual hormones influence neoplastic diseases by altering the DNA methylation levels ( 37 , 38 ). Estrogen induces decreased thymic autoimmune regulator ( AIRE ) expression by increasing the number of methylation sites within the AIRE promoter ( 39 ). MDFI has been considered as a potential estrogen-associated gene in lung tumorigenesis ( 40 ); however, further investigation is required to verify the hypothesis of the present study.…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of MDFI promoter with NSCLC is specific for females, non‑smokers and people younger than 65

Chen

et al. 2018

Oncol Lett

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Non-small cell lung carcinoma (NSCLC) is a major subtype of lung cancer. Aberrant DNA methylation has been frequently observed in NSCLC. The aim of the present study was to investigate the role of MyoD family inhibitor (MDFI) methylation in NSCLC. Formalin-fixed paraffin-embedded tumor tissues and adjacent non-cancerous tissues were collected from a total of 111 patients with NSCLC. A methylation assay was performed using the quantitative methylation-specific polymerase chain reaction method. The percentage of methylated reference was used to represent the methylation level of the MDFI promoter. Data mining of a dataset from The Cancer Genome Atlas (TCGA) demonstrated that MDFI promoter methylation levels were significantly increased in 830 tumor tissues compared with 75 non-tumor tissues (P=0.012). However, the results on tissues obtained in the present study indicated that the MDFI promoter methylation levels in tumor tissues were not significantly different compared with those in the adjacent non-tumor tissues (P=0.159). Subsequent breakdown analysis identified that higher MDFI promoter methylation levels were significantly associated with NSCLC in females (P=0.031), but not in males (P=0.832). Age-based subgroup analysis demonstrated that higher MDFI promoter methylation levels were significantly associated with NSCLC in younger patients (≤65 years; P=0.003), but not in older patients (P=0.327). In addition, the association of MDFI methylation with NSCLC was significant in non-smokers (P=0.014), but not in smokers (P=0.832). Similar results also have been determined from subgroup analysis of the TCGA datasets. The Gene Expression Omnibus database indicated MDFI expression restoration in partial lung cancer cell lines (H1299 and Hotz) following demethylation treatment. However, it was identified that MDFI promoter hypermethylation was not significantly associated with prognosis of NSCLC (P>0.05). In conclusion, the present study indicated that the association of higher methylation of the MDFI promoter with NSCLC may be specific to females, non-smokers and people aged ≤65.

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Prédisposition aux pathologies auto-immmunes

Cited by 9 publications

References 41 publications

Prognostic value of B cells in cutaneous melanoma

Prognostic value of B cells in cutaneous melanoma

Real-world questions and concerns about disease-modifying antirheumatic drugs (DMARDs): a retrospective analysis of questions to a medicine call center

Hypermethylation of MDFI promoter with NSCLC is specific for females, non‑smokers and people younger than 65

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