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Looking into a Crystal Ball: An Interview with Ron Crystal.

Hum Gene Ther Clin Dev. 2019 09;30(3):97-101

Authors: Davies K

PMID: 31535944 [PubMed – indexed for MEDLINE]

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ISSAID/EMQN Best Practice Guidelines for the Genetic Diagnosis of Monogenic Autoinflammatory Diseases in the Next-Generation Sequencing Era.

Clin Chem. 2020 Mar 16;:

Authors: Shinar Y, Ceccherini I, Rowczenio D, Aksentijevich I, Arostegui J, Ben-Chétrit E, Boursier G, Gattorno M, Hayrapetyan H, Ida H, Kanazawa N, Lachmann HJ, Mensa-Vilaro A, Nishikomori R, Oberkanins C, Obici L, Ohara O, Ozen S, Sarkisian T, Sheils K, Wolstenholme N, Zonneveld-Huijssoon E, van Gijn ME, Touitou I

Abstract
BACKGROUND: Monogenic autoinflammatory diseases are caused by pathogenic variants in genes that regulate innate immune responses, and are characterized by sterile systemic inflammatory episodes. Since symptoms can overlap within this rapidly expanding disease category, accurate genetic diagnosis is of the utmost importance to initiate early inflammation-targeted treatment and prevent clinically significant or life-threatening complications. Initial recommendations for the genetic diagnosis of autoinflammatory diseases were limited to a gene-by-gene diagnosis strategy based on the Sanger method, and restricted to the 4 prototypic recurrent fevers (MEFV, MVK, TNFRSF1A, and NLRP3 genes). The development of best practices guidelines integrating critical recent discoveries has become essential.
METHODS: The preparatory steps included 2 online surveys and pathogenicity annotation of newly recommended genes. The current guidelines were drafted by European Molecular Genetics Quality Network members, then discussed by a panel of experts of the International Society for Systemic Autoinflammatory Diseases during a consensus meeting.
RESULTS: In these guidelines, we combine the diagnostic strength of next-generation sequencing and recommendations to 4 more recently identified genes (ADA2, NOD2, PSTPIP1, and TNFAIP3), nonclassical pathogenic genetic alterations, and atypical phenotypes. We present a referral-based decision tree for test scope and method (Sanger versus next-generation sequencing) and recommend on complementary explorations for mosaicism, copy-number variants, and gene dose. A genotype table based on the 5-category variant pathogenicity classification provides the clinical significance of prototypic genotypes per gene and disease.
CONCLUSIONS: These guidelines will orient and assist geneticists and health practitioners in providing up-to-date and appropriate diagnosis to their patients.

PMID: 32176780 [PubMed – as supplied by publisher]

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Risk factors of the efficacy of hepatitis B vaccine in health-care workers.

J Res Med Sci. 2020;25:15

Authors: Salehi H, Salehi M, Kalbasi N, Salehi M, Sharifian J, Salehi MM

Abstract
Background: Conventional hepatitis B virus vaccination fails to achieve efficient protection in about 5%-10% of the world population. Different factors influence the immunogenicity of hepatitis B vaccine. This study aimed to evaluate these factors in health-care workers.
Materials and Methods: This was a descriptive study which was implemented among 140 of medical and dental staff working as health-care workers who were low responder after vaccination entered the study.
Results: Age (>40 years), weight (body mass index >25), immunodeficiency diseases, (primary immune deficiency and immunosuppressant drugs), diabetes mellitus, and smoking were the important factors.
Conclusion: In the high-risk group of hepatitis B disease, the risk factors of immunogenicity must be evaluated at vaccination and check titers of antibody after vaccination.

PMID: 32174987 [PubMed]

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Age Distribution of Multiple Functionally Relevant Subsets of CD4+ T Cells in Human Blood Using a Standardized and Validated 14-Color EuroFlow Immune Monitoring Tube.

Front Immunol. 2020;11:166

Authors: Botafogo V, Pérez-Andres M, Jara-Acevedo M, Bárcena P, Grigore G, Hernández-Delgado A, Damasceno D, Comans S, Blanco E, Romero A, Arriba-Méndez S, Gastaca-Abasolo I, Pedreira CE, van Gaans-van den Brink JAM, Corbiere V, Mascart F, van Els CACM, Barkoff AM, Mayado A, van Dongen JJM, Almeida J, Orfao A

Abstract
CD4+ T cells comprise multiple functionally distinct cell populations that play a key role in immunity. Despite blood monitoring of CD4+ T-cell subsets is of potential clinical utility, no standardized and validated approaches have been proposed so far. The aim of this study was to design and validate a single 14-color antibody combination for sensitive and reproducible flow cytometry monitoring of CD4+ T-cell populations in human blood to establish normal age-related reference values and evaluate the presence of potentially altered profiles in three distinct disease models-monoclonal B-cell lymphocytosis (MBL), systemic mastocytosis (SM), and common variable immunodeficiency (CVID). Overall, 145 blood samples from healthy donors were used to design and validate a 14-color antibody combination based on extensive reagent testing in multiple cycles of design-testing-evaluation-redesign, combined with in vitro functional studies, gene expression profiling, and multicentric evaluation of manual vs. automated gating. Fifteen cord blood and 98 blood samples from healthy donors (aged 0-89 years) were used to establish reference values, and another 25 blood samples were evaluated for detecting potentially altered CD4 T-cell subset profiles in MBL (n = 8), SM (n = 7), and CVID (n = 10). The 14-color tube can identify ≥89 different CD4+ T-cell populations in blood, as validated with high multicenter reproducibility, particularly when software-guided automated (vs. manual expert-based) gating was used. Furthermore, age-related reference values were established, which reflect different kinetics for distinct subsets: progressive increase of naïve T cells, T-helper (Th)1, Th17, follicular helper T (TFH) cells, and regulatory T cells (Tregs) from birth until 2 years, followed by a decrease of naïve T cells, Th2, and Tregs in older children and a subsequent increase in multiple Th-cell subsets toward late adulthood. Altered and unique CD4+ T-cell subset profiles were detected in two of the three disease models evaluated (SM and CVID). In summary, the EuroFlow immune monitoring TCD4 tube allows fast, automated, and reproducible identification of ≥89 subsets of CD4+ blood T cells, with different kinetics throughout life. These results set the basis for in-depth T-cell monitoring in different disease and therapeutic conditions.

PMID: 32174910 [PubMed – in process]

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Sodium butyrate modulates gut microbiota and immune response in colorectal cancer liver metastatic mice.

Cell Biol Toxicol. 2020 Mar 14;:

Authors: Ma X, Zhou Z, Zhang X, Fan M, Hong Y, Feng Y, Dong Q, Diao H, Wang G

Abstract
Colorectal cancer (CRC) liver metastasis (CLM) is the leading death cause of CRC patients, but there is no satisfied approach to treat CLM. Gut microbiota plays a pivotal role in CRC initiation and development. Targeting dysbiosis of the gut microbiota might open up new opportunities for CLM treatment. Here, we investigated the efficacy of sodium butyrate (NaB), a major product of gut microbial fermentation, in modulating gut microbiota in CLM mice. NaB supplement decreased mouse colon cancer CT26 cell liver metastasis in intrasplenic tumor injection model of BALB/c mice. Using 16S rRNA gene sequencing, we found altered microbiota composition in CLM mice, characterized by increases of Firmicutes and Proteobacteria. NaB beneficially changed dysbiosis in CLM mice. Functional analysis of the KEGG pathways showed that NaB changed pathways related to immune system diseases and primary immunodeficiency in CLM mice. In addition, NaB decreased T regulatory cells and increased natural killer T cells and T helper 17 cells, accordingly decreased IL-10 and increased IL-17 secretion in CLM mice liver. In conclusion, NaB beneficially modulated gut microbiota and improved host immune response in CLM mice. These findings demonstrate the therapeutic potential of NaB in CLM treatment.

PMID: 32172331 [PubMed – as supplied by publisher]

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