Research

Liver transcriptome analysis and de novo annotation of the orange-spotted groupers (Epinephelus coioides) under cold stress.

Comp Biochem Physiol Part D Genomics Proteomics. 2018 Dec 27;29:264-273

Authors: Sun Z, Tan X, Xu M, Liu Q, Ye H, Zou C, Ye C

Abstract
Cold stress has caused great economic loss in fish culture worldwide. Orange-spotted grouper (Epinephelus coioides) is one of the most serious lost aquatic animals in 2016 cold fronts in South China. However, the molecular mechanism of grouper’s cold resistance has remained largely unknown. In the present study, HiSeq™2000 (Illumina) was used to analyze the transcriptomic profiles of the liver from grouper under control temperature (CT, 28 °C) and low temperature (LT, 13 °C). Two normalized liver cDNA libraries of CT and LT groups were created. We obtained 51,944,970 and 51,905,036 clean reads from CT and LT groups, respectively. Comparing the LT group to the CT group, a total of 5905 significantly differentially expressed genes (DEGs) were identified, including 2093 up-regulated unigenes and 3812 down-regulated unigenes. GO annotation and functional enrichment analysis indicated that all of the DEGs were classified into three categories: biological process (23 subclasses), cellular component (18 subclasses) and molecular function (13 subclasses). KEGG analysis of the DEGs showed that 2732 DEGs were annotated to 253 signaling pathways. The most highly enriched pathways were cell adhesion molecules, Staphylococcus aureus infection, PPAR signaling pathway, Vibrio cholerae infection, primary immunodeficiency, fatty acid elongation, and we found cold stress mainly affects immunity, metabolic and signal transduction. Thirteen of the DEGs were further validated by qRT-PCR. Our results provide valuable information for further analysis of the mechanisms of groupers response under cold stress.

PMID: 30641323 [PubMed – as supplied by publisher]

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Now Is the Time to Use Molecular Gene Testing for the Diagnosis of Primary Immune Deficiencies.

J Allergy Clin Immunol Pract. 2019 Jan 10;:

Authors: Heimall J

Abstract
The discovery of chromosomes, genes, and DNA in the early 20th century paved the way for the development of techniques to examine the role of these elements in disease pathogenesis. Since the start of the 21st century, genetic testing and particularly next-generation sequencing has allowed for a rapid rate of gene disease associations for a broad range of primary immunodeficiency patients. At the same time, biologic and small molecule-based therapies targeting specific molecular pathways have been developed and are being applied clinically and in research settings to treat genetically defined immunodeficiencies. In recent years, both the American Academy of Allergy Asthma and Immunology and the Clinical Immunology Society have recommended the use of genetic testing for diagnosis, therapy guidance, and genetic counseling in patients with clinical symptoms of primary immunodeficiency.

PMID: 30639929 [PubMed – as supplied by publisher]

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Genetic diagnosis of primary immunodeficiencies: a survey of the French national registry.

J Allergy Clin Immunol. 2019 Jan 09;:

Authors: Mahlaoui N, Picard C, Bach P, Costes L, Courteille V, Ranohavimparany A, Alcaïs A, Jais JP, Fischer A, CEREDIH French PID study group

Abstract
The report describes the status of genetic diagnosis of PID based on a national registry. It shows that a genetic diagnosis has been achieved in half of them, reaching almost 80% of all PID but B cell immunodeficiencies.

PMID: 30639347 [PubMed – as supplied by publisher]

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Infantile-onset inflammatory bowel disease in a patient with Hermansky-Pudlak syndrome: a case report.

BMC Gastroenterol. 2019 Jan 11;19(1):9

Authors: Ishihara J, Mizuochi T, Uchida T, Takaki Y, Konishi KI, Joo M, Takahashi Y, Yoshioka S, Kusano H, Sasahara Y, Yamashita Y

Abstract
BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare, genetically heterogeneous disorder that manifests oculocutaneous albinism together with bleeding diatheses that reflect a platelet storage pool deficiency. Ten genetic subtypes of this autosomal recessive condition have been described to date. Some patients with Hermansky-Pudlak syndrome type 1, 4, or 6 develop Crohn’s-like inflammatory bowel disease at any age including early childhood, but most often in adolescence or young adulthood. Here we report infantile-onset of inflammatory bowel disease in a patient with Hermansky-Pudlak syndrome type 1 who responded to infliximab.
CASE PRESENTATION: A Japanese boy, the second child of non-consanguineous healthy parents, was born with chalky white skin, silvery-white hair, and gray eyes, representing oculocutaneous albinism. He developed frequent diarrhea and fever accompanied by weight loss at 6 months, and was diagnosed with Crohn’s-like inflammatory bowel disease based on the endoscopic finding of longitudinal ulcerations in the colon and the histopathologic finding of nonspecific chronic inflammation without granulomas at the age of 11 months. Treatment with an elemental diet, salazosulfapyridine, and corticosteroids failed to improve clinical or laboratory abnormalities, and the diarrhea became bloody. At 13 months he began treatment with infliximab, which produced marked improvement followed by clinical remission. Endoscopy at 20 months demonstrated healing of the colonic mucosa. At 22 months he is in sustained clinical remission receiving only infliximab. Because albinism with inflammatory bowel disease suggested Hermansky-Pudlak syndrome, we performed genetic screening using next-generation sequencing in a targeted gene panel analysis for primary immunodeficiency disease and/or inflammatory bowel disease. The patient proved to have a compound heterozygous mutation of the HPS1 gene resulting in Hermansky-Pudlak syndrome type 1.
CONCLUSIONS: We consider this report to be the first account of type 1 Hermansky-Pudlak syndrome with infantile-onset of inflammatory bowel disease. Early administration of infliximab was effective. We recommend next-generation sequencing for patients with very early-onset inflammatory bowel disease suspected to be monogenic.

PMID: 30634918 [PubMed – in process]

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Juvenile ecthyma gangrenosum caused by Pseudomonas aeruginosa revealing an underlying neutropenia: case report and review of the literature.

J Eur Acad Dermatol Venereol. 2019 Jan 11;:

Authors: Wuyts L, Wojciechowski M, Maes P, Matthieu L, Lambert J, Aerts O

Abstract
BACKGROUND: Ecthyma gangrenosum (EG) is characterized by the occurrence of erythematous, violaceous or hemorrhagic macules and/or vesicles, often evolving into necrotic ulcers, with a central gray-black eschar. It is a rare skin condition, usually occurring in immunocompromised patients suffering from bacterial sepsis caused by Pseudomonas aeruginosa. However, seemingly healthy children have been diagnosed with this skin disease as well.
OBJECTIVES: We report the work-up of a case of vulvar EG caused by Pseudomonas aeruginosa in a toddler, which led to a diagnosis of an underlying neutropenia. Moreover, we provide a brief literature review on those cases of EG where an underlying primary immunodeficiency, neutropenia in particular, was eventually diagnosed.
METHODS: A one-and-a-half year old girl presented with a history of recurrent (respiratory) infections and the sporadic occurrence of purpuric, vulvar ulcers. Work-up consisted of microbiological and haematological investigations, including repeated blood analyses.
RESULTS: Bacterial swabs from the vulvar ulcers showed the growth of Pseudomonas aeruginosa. No concomitant sepsis was present, but laboratory investigations pointed towards a cyclic neutropenia, coinciding with the occurrence of the EG lesions. Topical gentamicine ointment allowed the skin lesions to heal faster. Following the administration of granulocyte-colony stimulating factor (GCS-F), the girl experienced less infections in general and had no recurrence of EG lesions in particular. Treatment with GCS-F could eventually be stopped, and the neutropenia, ultimately transient in nature, completely resolved.
CONCLUSION: Children presenting with (anogenital) EG should always alert a physician to consider a potentially underlying immunodeficiency, neutropenia in particular. This article is protected by copyright. All rights reserved.

PMID: 30633375 [PubMed – as supplied by publisher]

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Inflammatory bowel diseases and primary immunodeficiency diseases.

Immunol Med. 2019 Jan 11;:1-8

Authors: Kanegane H

Abstract
Recent advances in molecular biology have provided important insights into the genetic background of various inflammatory diseases. In particular, genome-wide association studies of inflammatory diseases have revealed genetic loci that play critical roles in the pathology of inflammation. Whole-exome and whole-genome sequencing analyses have also identified more than 300 causative genes for primary immunodeficiency diseases (PIDs). Some genetic loci that are associated with inflammatory diseases are mutated in PIDs, suggesting close relationships between inflammation and PIDs. Inflammatory diseases for which genetic associations have been described include inflammatory bowel disease (IBD), multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus, and systemic lupus erythematosus. Herein, I discuss about the genetic interactions between IBD and PIDs.

PMID: 30632919 [PubMed – as supplied by publisher]

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Proteome analysis of human neutrophil granulocytes from patients with monogenic disease using data-independent acquisition.

Mol Cell Proteomics. 2019 Jan 10;:

Authors: Grabowski P, Hesse S, Hollizeck S, Rohlfs M, Behrends U, Sherkat R, Tamary H, Ünal E, Somech R, Patıroğlu T, Canzar S, van der Werff Ten Bosch J, Klein C, Rappsilber J

Abstract
Neutrophil granulocytes are critical mediators of innate immunity and tissue regeneration. Rare diseases of neutrophil granulocytes may affect their differentiation and/or functions. However, there are very few validated diagnostic tests assessing the functions of neutrophil granulocytes in these diseases. Here, we set out to probe omics analysis as a novel diagnostic platform for patients with defective differentiation and function of neutrophil granulocytes. We analyzed highly purified neutrophil granulocytes from 68 healthy individuals and 16 patients with rare monogenic diseases. Cells were isolated from fresh venous blood (purity >99%) and used to create a spectral library covering almost 8000 proteins using strong cation exchange fractionation. Patient neutrophil samples were then analyzed by data-independent acquisition proteomics, quantifying 4154 proteins in each sample. Neutrophils with mutations in the neutrophil elastase gene ELANE, showed large proteome changes that suggest these mutations may affect maturation of neutrophil granulocytes and initiate misfolded protein response and cellular stress mechanisms. In contrast, only few proteins changed in patients with leukocyte adhesion deficiency (LAD) and chronic granulomatous disease (CGD). Strikingly, neutrophil transcriptome analysis showed no correlation with its proteome. In case of two patients with undetermined genetic causes, proteome analysis guided the targeted genetic diagnostics and uncovered the underlying genomic mutations. Data-independent acquisition proteomics may help to define novel pathomechanisms in neutrophil diseases and provide a clinically useful diagnostic dimension.

PMID: 30630937 [PubMed – as supplied by publisher]

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The Pattern of Malignancies in Down Syndrome and Its Potential Context With the Immune System.

Front Immunol. 2018;9:3058

Authors: Satgé D, Seidel MG

Abstract
The immune surveillance theory of cancer posits that the body’s immune system detects and destroys randomly occurring malignant cells. This theory is based on the observation of the increased frequency of malignancies in primary and secondary immunodeficiencies, and is supported by the successful demonstration of immune augmentation in current oncological immune therapy approaches. We review this model in the context of Down syndrome (DS), a condition with a unique tumor profile and various immune defects. Children and adults with DS are more prone to infections due to anatomical reasons and a varying degree of T- and B-cell maturation defects, NK cell dysfunction, and chemotactic or phagocytic abnormalities. However, despite an increased incidence of lymphoblastic and myeloblastic leukemia of infants and children with DS, individuals with DS have a globally decreased incidence of solid tumors as compared to age-adjusted non-DS controls. Additionally, cancers that have been considered “proof of immune therapy principles,” such as renal carcinoma, small cell lung carcinoma, and malignant melanoma, are less frequent in adults with DS compared to the general population. Thus, despite the combination of an increased risk of leukemia with detectable immune biological abnormalities and a clinical immunodeficiency, people with DS appear to be protected against many cancers. This observation does not support the immune surveillance theory in the context of DS and indicates a potential tumor-suppressive role for trisomy 21 in non-hematological malignancies.

PMID: 30631328 [PubMed – in process]

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[Clinical and genetic manifestations of immunodeficiency, centromeric instability, and facial anomalies syndrome: a case report and literature review].

Zhonghua Er Ke Za Zhi. 2019 Jan 02;57(1):55-59

Authors: Hu SC, Wang YB, Sun Q, Liu XR, Sun LL, Cui GM

Abstract
Objective: To analyze the clinical and genetic features of immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome with a case report and literature review. Methods: The clinical data and genetic test of a girl diagnosed with ICF syndrome in the Department of Nephrology and Immunology in Qingdao Women and Children’s Hospital in December 2016 were extracted and analyzed. “ICF syndrome” “immunodeficiency, centromeric instability and facial anomalies syndrome” “ICF syndrome and DNMT3B” were used as key words to search Chinese databases and Pubmed for literature until March 2018, and the literature was reviewed. Results: A female patient aged 22 months old with ocular hypertelorism and low-set ears was admitted due to recurrent infection over one year. Laboratory tests showed humoral immune deficiency with IgG<1.34 g/L, IgA<0.060 g/L, and IgM<0.179 g/L, but normal cellular immunity (total T lymphocyte 0.503, hepler T lymphocyte 0.328, cytotoxic T lymphocyte 0.166, natural killer cell 0.184, total B lymphocyte 0.276). Whole-exome sequencing revealed a de novo heterozygous splice site mutation c.922-2A>G in intron 8, and a de novo heterozygous missense mutation c.2477G>A in exon 23 of DNMT3B gene. Chromosome karyotype analysis showed 46, XX, with 64 out of 100 karyotypes showing centromere instability in chromosome 1. Five papers were found which were all in English, with total of 29 patients. Forty-three mutations were reported, including 34 missense, 2 deletion, 1 insertion, 6 splice site mutations. Eleven patients had complex heterozygosis mutations. All patients had centromere instability, humoral immune deficiency and facial dysplasia which were mainly ocular hypertelorism and low-set ears. Most patients had language and motor development delay, and a few were combined with mental retardation. Conclusions: ICF syndrome is a rare autosomal recessive primary immunodeficiency with classic clinical triad manifestations. De novo mutation of DNMT3B gene is one of etiologies according to genetic test.

PMID: 30630233 [PubMed – in process]

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