- Epstein-Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS) Immunodeficiency. [Review]
- FIFront Immunol 2017; 8:2005
- Activated PI3Kδ Syndrome (APDS) is an inherited immune disorder caused by heterozygous, gain-of-function mutations in the genes encoding the phosphoinositide 3-kinase delta (PI3Kδ) subunits p110δ or ...
Activated PI3Kδ Syndrome (APDS) is an inherited immune disorder caused by heterozygous, gain-of-function mutations in the genes encoding the phosphoinositide 3-kinase delta (PI3Kδ) subunits p110δ or p85δ. This recently described primary immunodeficiency disease (PID) is characterized by recurrent sinopulmonary infections, lymphoproliferation, and susceptibility to herpesviruses, with Epstein-Barr virus (EBV) infection being most notable. A broad range of PIDs having disparate, molecularly defined genetic etiology can cause susceptibility to EBV, lymphoproliferative disease, and lymphoma. Historically, PID patients with loss-of-function mutations causing defective cell-mediated cytotoxicity or antigen receptor signaling were found to be highly susceptible to pathological EBV infection. By contrast, the gain of function in PI3K signaling observed in APDS patients paradoxically renders these patients susceptible to EBV, though the underlying mechanisms are incompletely understood. At a cellular level, APDS patients exhibit deranged B lymphocyte development and defects in class switch recombination, which generally lead to defective immunoglobulin production. Moreover, APDS patients also demonstrate an abnormal skewing of T cells toward terminal effectors with short telomeres and senescence markers. Here, we review APDS with a particular focus on how the altered lymphocyte biology in these patients may confer EBV susceptibility.
- Mutations in PI3K110δ cause impaired natural killer cell function partially rescued by rapamycin treatment. [Journal Article]
- JAJ Allergy Clin Immunol 2018 Jan 10
- CONCLUSIONS: We describe novel NK cell functional deficiency caused by PI3K110δ mutation, which is a likely contributor to the severe viremia observed in these patients. Rapamycin treatment partially restores NK cell function, providing a further rationale for its use in patients with this disease.
- Kartagener's syndrome: a case report. [Journal Article]
- JMJ Med Case Rep 2018 Jan 10; 12(1):5
- CONCLUSIONS: Patients with Kartagener's syndrome exist in Ethiopia as cases of chronic recurrent sinopulmonary infections. As there is no easy, reliable non-invasive diagnostic test for Kartagener's syndrome and the correct diagnosis is often delayed by years, it may cause chronic respiratory problems with reduced quality of life. Genetic counseling and fertility issues should be addressed once Kartagener's syndrome is diagnosed.
- [Cystic fibrosis in adults]. [Journal Article]
- VLVnitr Lek 2018; 63(11):834-842
- Cystic fibrosis (CF) is an inherited disease caused by mutations in the transmembrane conductance regulator (CFTR) gene. The disease leads to dysfunction of the exocrine glands with high concentratio...
Cystic fibrosis (CF) is an inherited disease caused by mutations in the transmembrane conductance regulator (CFTR) gene. The disease leads to dysfunction of the exocrine glands with high concentration of chloride in the sweat and formation of abnormally viscous mucus in the respiratory, digestive and reproductive tract. Chronic sinopulmonary disease, exocrine pancreatic insufficiency, liver disease, intestinal obstruction, impaired nutritional status, salt loss syndrome and male infertility dominates in the clinical presentation. The examination of sweat chloride concentration and mutations in the CFTR gene is used in CF diagnostics for detection of CFTR protein dysfunction. The treatment comprises especially respiratory physiotherapy with mucolytics inhalations, aggressive antibiotic therapy and high-calorie diet together with adequate pancreatic enzymes substitution. The prevention of airway infection with resistant bacterial pathogens, particularly Pseudomonas aeruginosa, is a fundamental measure. Significant recent progress include the use of newborn screening of CF and drugs targeted to individual CFTR gene mutations in the clinical practise. The prognosis of patients has improved due to using of modern therapeutic methods in CF treatment centres. Children born at present time have survival probability 40-50 years.Key words: adults - cystic fibrosis - diagnostics - therapy.
- Prospective investigation of FOXP1 syndrome. [Journal Article]
- MAMol Autism 2017; 8:57
- CONCLUSIONS: This study identifies novel FOXP1 mutations associated with FOXP1 syndrome, identifies recurrent mutations, and demonstrates significant clustering of missense mutations in the DNA-binding domain. Clinical findings confirm the role FOXP1 plays in development across multiple domains of functioning. The genetic findings can be incorporated into clinical genetics practice to improve accurate genetic diagnosis of FOXP1 syndrome and the clinical findings can inform monitoring and treatment of individuals with FOXP1 syndrome.
- GeneReviews® [BOOK]
- BOOKUniversity of Washington, Seattle: Seattle (WA)
- Poikiloderma with neutropenia (PN) is characterized by an inflammatory eczematous rash (ages 6-12 months) followed by post-inflammatory poikiloderma (age >2 years) and chronic noncyclic neutropenia t...
Poikiloderma with neutropenia (PN) is characterized by an inflammatory eczematous rash (ages 6-12 months) followed by post-inflammatory poikiloderma (age >2 years) and chronic noncyclic neutropenia typically associated with recurrent sinopulmonary infections in the first two years of life and (often) bronchiectasis. There is increased risk for myelodysplastic syndrome and, rarely, acute myelogenous leukemia. Other ectodermal findings include nail dystrophy and palmar/plantar hyperkeratosis. Most affected individuals also have reactive airway disease and some have short stature, hypogonadotropic hypogonadism, midfacial retrusion, calcinosis cutis, and non-healing skin ulcers.
- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Primary ciliary dyskinesia (PCD), formerly known as immotile cilia syndrome, is a disorder of motile cilia structure and function that results in chronic oto-sinopulmonary disease. Primary ciliary d...
Primary ciliary dyskinesia (PCD), formerly known as immotile cilia syndrome, is a disorder of motile cilia structure and function that results in chronic oto-sinopulmonary disease. Primary ciliary dyskinesia typically presents with respiratory distress in infants, early onset year-round cough, and nasal congestion. Primary ciliary dyskinesia diagnosis is challenging given lack of a single diagnostic test and the multitude of conditions that result in similar symptoms. Kartagener syndrome is a triad of chronic sinusitis, bronchiectasis, and situs inversus resulting from ciliary dyskinesia.
- Early diagnosis of PI3Kδ syndrome in a 2 years old girl with recurrent otitis and enlarged spleen. [Journal Article]
- ILImmunol Lett 2017; 190:279-281
- Heterozygous gain of function mutations in the gene encoding p110δ subunit of PI3K have been recently associated with activated PI3K-δ syndrome (APDS), a novel combined immune deficiency characterize...
Heterozygous gain of function mutations in the gene encoding p110δ subunit of PI3K have been recently associated with activated PI3K-δ syndrome (APDS), a novel combined immune deficiency characterized by recurrent sinopulmonary infections, lymphopenia, reduced class-switched memory B cells, lymphadenopathy, CMV and/or EBV viremia and EBV-related lymphoma. Here we report a dominant gain of function PIK3CD mutation (E1021K) in a patient presenting with recurrent otitis media, massive splenomegaly, and persistent EBV-viraemia. The immunological studies showed low IgA level, but normal IgM, IgG, and normal antibody response to diphtheria and tetanus toxoid vaccination. Analysis of B lymphocyte subsets revealed abnormal expansion of transitional B cells, and low percentage of switched CD27+IgD-and CD27+IgD+memory B cells. Analysis of T cell compartment unveiled prevalence of terminally differentiated cells. This study suggests that PIK3CD gain of function mutations should be suspected despite incomplete phenotype in patients with early onset splenomegaly, persistent EBV viremia and abnormal B and T cell subsets despite normal IgG levels. Currently the optimal treatment is still debated, but prompt management can hopefully diminish incidence of severe long-lasting sequelae (i.e. bronchiectasis, ear and sinus damage).
- [Good's syndrome. Report of case]. [Journal Article]
- RARev Alerg Mex 2017 Apr-Jun; 64(2):235-240
- CONCLUSIONS: Despite the variability of presentation, Good's syndrome should be suspected as part of the paraneoplastic manifestations of thymoma.
New Search Next
- Characteristics of Good's Syndrome in China: A Systematic Review. [Review]
- CMChin Med J (Engl) 2017 Jul 05; 130(13):1604-1609
- CONCLUSIONS: GS is a rare association of thymoma and immunodeficiency with a poor prognosis. Astute clinical acumen and increased awareness of the clinical and immunological profile of GS are needed to increase early diagnosis, that would benefit improved therapeutic effects.