Manish Butte

The Usefulness of Scintigraphic Studies in the Assessment of Asymptomatic Bowel Disease in Patients with Primary Antibody Diseases.

J Clin Med. 2020 Mar 30;9(4):

Authors: Milito C, Cinetto F, Megna V, Spadaro G, Quinti I, Liberatore M

Abstract
Enteropathy may be the first presentation of immunodeficiency or it may occur during the course of the disease and in association with malabsorption in patients affected by primary antibody diseases. For these patients, immunoglobulin G (IgG) replacement therapy prevents infectious and non-infectious complications. Nonetheless some patients cannot achieve optimal IgG trough levels, even when treated with high Ig doses in absence of protein-losing syndromes. We investigated seven patients affected by common variable immunodeficiencies (CVIDs) and treated with high Ig doses (600-800 mg/kg/month) showing low IgG trough level. Patients underwent abdominal scintigraphy with human polyclonal immunoglobulin G labeled with 99mTc and with white blood cells labeled by 111 Indium-oxinate to investigate asymptomatic bowel inflammation. A concentration of labeled leukocytes in abdominal segments greater than that observed with human polyclonal immunoglobulin G was evident only in one patient. In five patients a slight concentration of both radiopharmaceuticals was reported, due to mild intestinal inflammatory response. These data might be related to mild increase of capillary permeability in the absence of inflammation leukocyte mediated. This study discloses a new cause of IgG-accelerated catabolism due to inflammatory bowel conditions without diarrhea in CVID patients.

PMID: 32235478 [PubMed]

Powered by WPeMatico

Identification of Potential Biomarkers in Neonatal Sepsis by Establishing of a Competitive Endogenous RNA Network.

Comb Chem High Throughput Screen. 2020 Apr 01;:

Authors: Liu L, Wang H, Zhang X, Chen R

Abstract
BACKGROUND: Neonatal sepsis is a serious and difficult-to-diagnose systemic infectious disease occurring during the neonatal period.
OBJECTIVE: This study aimed to identify potential biomarkers of neonatal sepsis and explore its underlying mechanisms.
METHODS: We downloaded the neonatal sepsis-related gene profile GSE25504 from the NCBI Gene Expression Omnibus (GEO) database. The differentially expressed RNAs (DERs) were screened and identified using LIMMA. Then, the functions of the DERs were evaluated using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, a competing endogenous RNA (ceRNA) network was constructed and functional analyses were performed.
RESULTS: The initial screen identified 444 differentially expressed (DE)-mRNAs and 45 DE-lncRNAs. GO analysis showed that these DE-mRNAs were involved in immune response, defense response, and positive regulation of immune system process. KEGG analysis showed that these DE-mRNAs were enriched in 30 activated pathways and 6 suppressed pathways, and those with the highest scores were the IL-17 signaling pathway and ribosome, respectively. Next, 722 miRNAs associated with the identified lncRNAs were predicted using miRWalk. A ceRNA network was constructed that included 6 lncRNAs, 11 mRNAs, and 55 miRNAs. In this network, HCP5, LINC00638, XIST and TP53TG1 were hub nodes. Functional analysis of this network identified some essential immune functions, hematopoietic functions, osteoclast differentiation, and primary immunodeficiency as associated with neonatal sepsis.

PMID: 32233999 [PubMed – as supplied by publisher]

Powered by WPeMatico

[Identification of a novel CHS1/LYST variant in a Chinese pedigree affected with Chediak-Higashi syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2020 Apr 10;37(4):441-444

Authors: Meng J, Wang H, Qian X, Miao H, Zhu X, Yu Y, Le J, Gao S, Sun C, Qian M, Zhai X

Abstract
OBJECTIVE: To detect pathological variant in two patients with Chediak-Higashi syndrome (CHS) from a consanguineous family and to explore its genotype-phenotype correlation.
METHODS: Clinical data was collected for this pedigree. Genomic DNA was prepared from probands’ peripheral leukocytes and their relatives’ fingernail. Whole exome sequencing and Sanger sequencing were carried out to detect potential variant of the LYST gene.
RESULTS: The proband presented with partial oculocutaneous albinism, immunodeficiency and acidophilic inclusion body in bone marrow and blood smears. A novel homozygous nonsense variant c.8782C>T (p.Gln2928*) was identified in exon 34 of the LYST gene in the sib pair. The same variant was found to be in heterozygous status in 6 unaffected individuals from the pedigree.
CONCLUSION: Above result enriched the mutational spectrum of CHS and provided a basis for genetic counseling and prenatal diagnosis for this pedigree.

PMID: 32219832 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

[Cartilage-hair hypoplasia. A case report].

Rev Alerg Mex. 2019 Jul-Sep;66(3):379-383

Authors: Staines-Boones TA, González-Villarreal MG, Hernández-Fernández C

Abstract
BACKGROUND: Cartilage-hair hypoplasia is a rare autosomal recessive disease, which is characterized by metaphyseal chondrodysplasia and thin hair. It can be accompanied by immunological disorders in varying degrees.
CLINICAL CASE: The case of a 35-month-old girl is described. Since her birth, with growth restriction, she has developed pneumonia eleven times, malabsorption syndrome and aganglionic megacolon, which is why she was diagnosed with cartilage-hair hypoplasia, with expression of non-severe combined immunodeficiency. The decision was to proceed with hematopoietic stem cell transplantation. At the time of this report, the patient was free from infectious processes.
CONCLUSION: Cartilage-hair hypoplasia is a condition with diverse clinical features and different degrees of immunodeficiency. As part of the treatment, it is possible to perform haematopoietic stem cell transplantation.

PMID: 31606024 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

Role of IRF8 in immune cells functions, protection against infections, and susceptibility to inflammatory diseases.

Hum Genet. 2020 Mar 30;:

Authors: Salem S, Salem D, Gros P

Abstract
The transcription factor IRF8 (ICSBP) is required for the development and maturation of myeloid cells (dendritic cells, monocytes, macrophages), and for expression of intrinsic anti-microbial function such as antigen capture, processing and presentation to lymphoid cells, and for activation of these cells in response to cytokines and pro-inflammatory stimuli (IFN-γ, IFN-β, LPS). IRF8 deficiency in humans causes a severe primary immunodeficiency presenting as susceptibility to infections, complete or severe depletion of blood dendritic cells (DC) subsets, depletion of CD14+ and CD16+ monocytes and reduced numbers and impaired activity of NK cells. In genome-wide association studies (GWAS), sequence variants near IRF8 are significant risk factors for multiple chronic inflammatory diseases in humans including inflammatory bowel disease, lupus, rheumatoid arthritis, multiple sclerosis, and several others. Recent studies have cataloged all the genes bound by and transcriptionally activated by IRF8 in myeloid cells, either alone or in combination with other transcription factors (PU.1, IRF1, STAT1) at steady state and in response to pro-inflammatory stimuli. This IRF1/IRF8 regulome comprises immune pathways such as antigen processing and presentation pathways, expression of costimulatory molecules, cytokines and chemokines, response to stimuli such as cytokine receptors, pathogen-associated molecular pattern receptors, TLRs and nucleotide-binding oligomerization domain-like receptor signaling pathways, and small antiviral GTPases. Members of the IRF8/IRF1 regulome are over-represented amongst genes in which mutations cause primary immunodeficiencies, and are specifically enriched at GWAS loci associated with chronic inflammatory diseases in humans. These recent studies highlight a critical role of IRF8 in the activity of several immune cell types for protection against infections, but also in pathological inflammation associated with common human inflammatory conditions.

PMID: 32232558 [PubMed – as supplied by publisher]

Powered by WPeMatico

Magnesium: The overlooked electrolyte in blood cancers?

Blood Rev. 2020 Mar 27;:100676

Authors: Gile J, Ruan G, Abeykoon J, McMahon MM, Witzig T

Abstract
Magnesium is an important element that has essential roles in the regulation of cell growth, division, and differentiation. Mounting evidence in the literature suggests an association between hypomagnesemia and all-cause mortality. In addition, epidemiologic studies have demonstrated that a diet poor in magnesium increases the risk of developing cancer, highlighting its importance in the field of hematology and oncology. In solid malignancies, hypomagnesemia at diagnosis portends a worse prognosis. However, little is known about prognosis in patients with hypomagnesemia and blood cancers in general; lymphoma more specifically. Hypomagnesemia has been associated with a higher viral load of the Epstein Barr virus, a virus associated with a multitude of hematologic malignancies. The role of magnesium in the immune system has been further elucidated in studies of patients with a rare primary immunodeficiency known as XMEN disease (X-linked immunodeficiency with Magnesium defect, Epstein-Barr virus (EBV) infection, and Neoplasia disease). These patients have a mutation in the MAGT1 gene, which codes for a magnesium transporter. The mutation leads to impaired T cell activation and an increased risk of developing hematologic malignancies. In this review we discuss the relevance of magnesium as an electrolyte, current measurement techniques, and the known data related to cause and prognosis of blood cancers. The goal is to use these data to stimulate additional high-quality and well powered studies to further investigate the role of magnesium in preventing cancer and improving outcomes of patients with malignancy and concomitant magnesium deficiency.

PMID: 32229066 [PubMed – as supplied by publisher]

Powered by WPeMatico

Serum protein electrophoresis and complement deficiencies: a veteran but very versatile test in clinical laboratories.

Clin Chem Lab Med. 2019 07 26;57(8):e179-e182

Authors: Franco-Jarava C, Dieli-Crimi R, Vila-Pijoan G, Colobran R, Pujol-Borrell R, Hernández-González M

PMID: 30721140 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

Alterations in Immune-Related Genes as Potential Marker of Prognosis in Breast Cancer.

Front Oncol. 2020;10:333

Authors: Li B, Geng R, Wu Q, Yang Q, Sun S, Zhu S, Xu Z, Sun S

Abstract
The tumor microenvironment (TME) is a heterogeneous system that contributes to breast cancer progression. The Cancer Genome Atlas (TCGA) database provides global gene expression profiling data for further analysis of various malignancies, including breast cancer. Based on the ESTIMATE algorithm, immune and stromal scores were calculated according to immune or stromal components in the TME. We divided breast cancer cases into high- and low-score groups and identified differentially expressed genes (DEGs) that were significantly associated with overall survival. We performed enrichment analysis and constructed a protein-protein interaction network and found that the DEGs were mainly involved in primary immunodeficiency, T cell receptor signaling pathway and cytokine-cytokine receptor reaction. Furthermore, we explored the effect of aging on immune and stromal scores, which was validated by lower immune/stromal scores, lower infiltration of T cells and lower expression of immune checkpoints in the elder group. In conclusion, certain differentially expressed immune-related genes contribute to longer overall survival, and aging influences the immune microenvironment and immunotherapy efficacy by changing the tumor-infiltrating lymphocyte (TIL) abundance and checkpoint expression in breast cancer.

PMID: 32226776 [PubMed]

Powered by WPeMatico