Stanford Alliance for Primary Immunodeficiency
Stanford University
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A novel C1 inhibitor gene mutation in a family with hereditary angioedema: Use of genetic analysis to facilitate early diagnosis.
Allergol Int. 2020 01;69(1):148-149
Authors: Yokoyama K, Horiuchi T, Hashimura C, Yoshida A
PMID: 31409531 [PubMed – indexed for MEDLINE]
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Disseminated Bacillus-Calmette-Guérin infections and primary immunodeficiency disorders in Singapore: A single center 15-year retrospective review.
Int J Infect Dis. 2020 Jun 01;:
Authors: Ong RYL, Chew SJ, Liew WK, Thoon KC, Chong CY, Yung CF, Sng LH, Tan AM, Bhattacharyya R, Chan SB, Jamuar SS, Lim JY, Li J, Nadua KD, Kam KQ, Tan NW
Abstract
BACKGROUND: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs).
METHODS: A 15-year retrospective review was conducted in KK Women’s and Children’s Hospital in Singapore, from January 2003 to October 2017.
RESULTS: Ten patients were identified, mostly male (60.0%). The median age at presentation of systemic signs and symptoms, was 4.0 (0.5 – 27.9) months. All the patients had underlying PIDs – five with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), and one with STAT-1 gain-of function mutation. Definitive BCGosis was confirmed in all patients by identification of Mycobacterium bovis subsbp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsbp BCG are as follows: Rifampicin (88.8%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent haematopoietic stem cell transplant (HSCT), of which 3 (60%) have recovered. Overall mortality was 50.0%.
CONCLUSION: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.
PMID: 32497805 [PubMed – as supplied by publisher]
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Autosomal dominant hyper-IgE syndrome: When hematopoietic stem cell transplantation should be considered?
Pediatr Transplant. 2020 Jun 04;:e13699
Authors: Oikonomopoulou C, Goussetis E
Abstract
AD-HIES or Job’s syndrome is a primary immunodeficiency, caused by dominant negative mutations in signal transducer and activator of transcription (STAT) 3. The syndrome is characterized by infectious, immunologic, and non-immunologic manifestations and is associated with significant morbidity, mortality, and development of lymphomas. What has not yet been elucidated is the role of HSCT in the disease treatment spectrum. We review published cases of patients with AD-HIES that underwent HSCT and attempt to clarify at what stage HSCT should be considered and what are the complications.
PMID: 32497403 [PubMed – as supplied by publisher]
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Treatment of facial myiasis in an elderly patient with oral squamous cell carcinoma: Case report.
Int J Surg Case Rep. 2020 May 21;71:260-265
Authors: Lazaro SA, Gordillo Yépez FD, De Carli JP, Trentin MS, Dogenski LC, De Conto F
Abstract
Myiasis is caused by the infestation of fly larvae in human tissues and it presents immunodeficiency, poor hygiene, or malignant neoplasias as predisposing chronic diseases.
OBJECTIVE: To describe a clinical case of myiasis associated with oral squamous cell carcinoma (OSCC) in an elderly patient.
CASE PRESENTATION: A 60-year-old male, black, smoker, and alcoholic patient with OSCC, who refused initial cancer treatment and sought hospital care with an extensive facial lesion and approximately 150 larvae in the extraoral region. The treatment was given through the administration of 6 mg of Ivermectin associated with the surgical removal of the larvae. Subsequently, palliative chemotherapy began.
DISCUSSION: Myiasis can sometimes be associated with OSCC and it commonly occurs in individuals who live in unhealthy locations and present poor hygiene and low immunity. In addition to medication, the surgical removal of the larvae is important in the treatment of myiasis.
CONCLUSION: Patient adherence to cancer treatment is essential to avoid the negative evolution of the tumor. The social component linked to the development of myiasis makes it an important public health topic, as it is related directly to the lack of primary care. Surgical and drug treatments are required to cure myiasis.
PMID: 32492640 [PubMed – as supplied by publisher]
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X-linked Agammaglobulinemia Presenting with Multiviral Pneumonia.
Cureus. 2020 Apr 29;12(4):e7884
Authors: Arroyo-Martinez YM, Saindon M, Raina JS
Abstract
X-linked agammaglobulinemia (XLA) is a primary humoral immunodeficiency characterized by severe hypogammaglobulinemia and increased risk of infection. The genetic condition results from a mutation in the Bruton tyrosine kinase (BTK) gene located on the X chromosome leading to a near absence of B cells. Patients affected by XLA are most commonly predisposed to frequent and severe bacterial infections. However, here we report the case of a 20-year-old male with XLA who presented with viral pneumonia with multiple pathogens. This coexistence has been rarely reported. The patient received intravenous immunoglobulin therapy with noted significant improvement in the two weeks of follow-up. His clinical history supports the hypothesis of increased susceptibility to viral pathogens in the absence of immunoglobulin therapy. The humoral defect is the cornerstone of this phenomenon. This case presents the importance of multiviral causes for patients with recurrent episodes of pneumonia in an immunocompromised state.
PMID: 32489738 [PubMed]
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Comprehensive investigation of an in-hospital transmission cluster of a symptomatic SARS-CoV-2-positive physician among patients and healthcare workers in Germany.
Infect Control Hosp Epidemiol. 2020 Jun 03;:1-12
Authors: Wendt R, Nagel S, Nickel O, Wolf J, Kalbitz S, Kaiser T, Borte S, Lübbert C
PMID: 32489162 [PubMed – as supplied by publisher]
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Comprehensive Targeted Sequencing Identifies Monogenic Disorders in Patients With Early-onset Refractory Diarrhea.
J Pediatr Gastroenterol Nutr. 2020 Jun 01;:
Authors: Uchida T, Suzuki T, Kikuchi A, Kakuta F, Ishige T, Nakayama Y, Kanegane H, Etani Y, Mizuochi T, Fujiwara SI, Nambu R, Suyama K, Tanaka M, Yoden A, Abukawa D, Sasahara Y, Kure S
Abstract
OBJECTIVES: Causes of early-onset refractory diarrhea include exudative diarrhea associated with very early-onset inflammatory bowel diseases, osmotic or secretory diarrhea, and protein-losing enteropathy. Monogenic disorders are included in these diseases, yet a comprehensive genetic analysis has not been fully established.
METHODS: We established targeted gene panels covering all responsible genes for early-onset diarrhea. In total, 108 patients from 15 institutions were enrolled in this study. We collected clinical data from all patients. Seventy-three patients with exudative diarrhea, 4 with osmotic or secretory diarrhea and 8 with protein-losing enteropathy were subjected to genetic analysis.
RESULTS: A total of 15 out of the 108 enrolled patients (13.9%) were identified as monogenic. We identified 1 patient with RELA, 2 with TNFAIP3, 1 with CTLA4, 1 with SLCO2A1, 4 with XIAP, 3 with IL10RA, 1 with HPS1, 1 with FOXP3, and 1 with CYBB gene mutations. We also identified 1 patient with NFKB2 and 1 with TERT mutations from the gene panel for primary immunodeficiency syndromes. The patient with refractory diarrhea caused by heterozygous truncated RelA protein expression is the first case identified worldwide, and functional analysis revealed that the mutation affected nuclear factor kappa B signaling. Genotypes were significantly associated with the clinical and pathological findings in each patient.
CONCLUSIONS: We identified variable monogenic diseases in the patients and found that genes responsible for primary immunodeficiency diseases were frequently involved in molecular pathogenesis. Comprehensive genetic analysis was useful for accurate molecular diagnosis, understanding of underlying pathogenesis, and selecting the optimal treatment for patients with early-onset refractory diarrhea.
PMID: 32487952 [PubMed – as supplied by publisher]
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DNA methylation in disease: Immunodeficiency, Centromeric instability, Facial anomalies syndrome.
Essays Biochem. 2019 12 20;63(6):773-783
Authors: Vukic M, Daxinger L
Abstract
DNA methylation is an epigenetic modification essential for normal mammalian development. Initially associated with gene silencing, more diverse roles for DNA methylation in the regulation of gene expression patterns are increasingly being recognized. Some of these insights come from studying the function of genes that are mutated in human diseases characterized by abnormal DNA methylation landscapes. The first disorder to be associated with congenital defects in DNA methylation was Immunodeficiency, Centromeric instability, Facial anomalies syndrome (ICF). The hallmark of this syndrome is hypomethylation of pericentromeric satellite repeats, with mutations in four genes: DNMT3B, ZBTB24, CDCA7 and HELLS, being linked to the disease. Here, we discuss recent progress in understanding the molecular interactions between these genes and consider current evidence for how aberrant DNA methylation may contribute to the abnormal phenotype present in ICF syndrome patients.
PMID: 31724723 [PubMed – indexed for MEDLINE]
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DNA methylation in satellite repeats disorders.
Essays Biochem. 2019 12 20;63(6):757-771
Authors: Francastel C, Magdinier F
Abstract
Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.
PMID: 31387943 [PubMed – indexed for MEDLINE]
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Severe cases of BCGosis-susceptible primary immunodeficiency diseases identified by next-generation sequencing: Implications for adjustment of BCG vaccination timing in China.
J Genet Genomics. 2020 Mar 30;:
Authors: Liu G, Xiao H, Liu L, Guo L, Guo R, Hu X, Hao C, Gui J, Jiao W, Xu F, Shen A, Li W
PMID: 32482412 [PubMed – as supplied by publisher]
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