Manish Butte

Dupilumab to treat severe atopic dermatitis in autosomal dominant hyper-IgE syndrome.

Clin Immunol. 2020 Apr 29;:108452

Authors: Sogkas G, Hirsch S, Jablonka A, Witte T, Schmidt RE, Atschekzei F

PMID: 32360519 [PubMed – as supplied by publisher]

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A twelve-gene signature for survival prediction in malignant melanoma patients.

Ann Transl Med. 2020 Mar;8(6):312

Authors: Song LB, Zhang QJ, Hou XY, Xiu YY, Chen L, Song NH, Lu Y

Abstract
Background: Melanoma is defined as a highly mutational heterogeneous disease containing numerous alternations of the molecule. However, due to the phenotypically and genetically heterogeneity of malignant melanoma, conventional clinical characteristics remain restricted or limited in the ability to accurately predict individual outcomes and survival. This study aimed to establish an accurate gene expression signature to predict melanoma prognosis.
Methods: In this study, we established an RNA sequencing-based 12-gene signature data of melanoma patients obtained from 2 independent databases: the Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. We evaluated the quality of each gene to predict survival conditions in each database by employing univariate and multivariate regression models. A prognostic risk score based on a prognostic signature was determined. This prognostic gene signature further classified patients into low-risk and high-risk groups.
Results: Based on a prognostic signature, a prognostic risk score was determined. This prognostic gene signature further divided the patients into low-risk and high-risk groups. In the chemotherapy and radiotherapy groups of the TCGA cohort and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) expression group in the GEO cohort, patients in the low-risk group had a longer survival duration compared to patients in the high-risk group. Nevertheless, the immunotherapy group in the TCGA database and neuroblastoma RAS viral oncogene homolog (NRAS) expression group in the GEO database had no significant differences in statistics. Moreover, this gene signature was associated with patient prognosis regardless of whether the Breslow depth was greater than or less than 3.75 mm. Stratified gene set enrichment analysis (GSEA) revealed that certain immune-related pathways, such as the T-cell signaling pathway, chemokine signaling pathway, and primary immunodeficiency, were significantly enriched in the low-risk group of both TCGA and GEO cohorts. This information implied the immune-related properties of the 12-gene signature.
Conclusions: Our study emphasizes the significance of the gene expression signature in that it may be an indispensable prognostic predictor in melanoma and has great potential for application in personalized treatment.

PMID: 32355756 [PubMed]

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Defective formation of IgA memory B cells, Th1 and Th17 cells in symptomatic patients with selective IgA deficiency.

Clin Transl Immunology. 2020 May;9(5):e1130

Authors: Grosserichter-Wagener C, Franco-Gallego A, Ahmadi F, Moncada-Vélez M, Dalm VA, Rojas JL, Orrego JC, Correa Vargas N, Hammarström L, Schreurs MW, Dik WA, van Hagen PM, Boon L, van Dongen JJ, van der Burg M, Pan-Hammarström Q, Franco JL, van Zelm MC

Abstract
Objective: Selective IgA deficiency (sIgAD) is the most common primary immunodeficiency in Western countries. Patients can suffer from recurrent infections and autoimmune diseases because of a largely unknown aetiology. To increase insights into the pathophysiology of the disease, we studied memory B and T cells and cytokine concentrations in peripheral blood.
Methods: We analysed 30 sIgAD patients (12 children, 18 adults) through detailed phenotyping of peripheral B-cell, CD8+ T-cell and CD4+ T-cell subsets, sequence analysis of IGA and IGG transcripts, in vitro B-cell activation and blood cytokine measurements.
Results: All patients had significantly decreased numbers of T-cell-dependent (TD; CD27+) and T-cell-independent (TI; CD27-) IgA memory B cells and increased CD21low B-cell numbers. IgM+IgD- memory B cells were decreased in children and normal in adult patients. IGA and IGG transcripts contained normal SHM levels. In sIgAD children, IGA transcripts more frequently used IGA2 than controls (58.5% vs. 25.1%), but not in adult patients. B-cell activation after in vitro stimulation was normal. However, adult sIgAD patients exhibited increased blood levels of TGF-β1, BAFF and APRIL, whereas they had decreased Th1 and Th17 cell numbers.
Conclusion: Impaired IgA memory formation in sIgAD patients is not due to a B-cell activation defect. Instead, decreased Th1 and Th17 cell numbers and high blood levels of BAFF, APRIL and TGF-β1 might reflect disturbed regulation of IgA responses in vivo.These insights into B-cell extrinsic immune defects suggest the need for a broader immunological focus on genomics and functional analyses to unravel the pathogenesis of sIgAD.

PMID: 32355559 [PubMed]

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Chronic mucocutaneous candidiasis: a rare diagnosis in paediatric dentistry.

Br J Oral Maxillofac Surg. 2020 Apr 26;:

Authors: Sanghvi R, Siddik D, Hullah E, Shah T, Carey B

Abstract
Chronic mucocutaneous candidiasis is a rare disorder that is characterised by chronic or recurrent superficial candida infection of skin, nails, and mucous membranes. We describe such a case in a young boy who failed to respond to conventional therapy. It highlights the important role of the dental team in assessment, treatment, and onwards referral.

PMID: 32349899 [PubMed – as supplied by publisher]

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Follow the Tennis Ball Like a Golden Retriever.

Stem Cells Dev. 2019 06 01;28(11):708

Authors: Nolta JA

PMID: 31090493 [PubMed – indexed for MEDLINE]

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