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https://www.readbyqxmd.com/read/29781065/correction-to-use-of-genetic-testing-for-primary-immunodeficiency-patients
#1
Jennifer R Heimall, David Hagin, Joud Hajjar, Sarah E Henrickson, Hillary S Hernandez-Trujillo, Yuval Itan, Lisa Kobrynski, Kenneth Paris, Troy R Torgerson, James W Verbsky, Richard L Wasserman, Elena W Y Hsieh, Jack J Bleesing, Janet S Chou, Monica G Lawrence, Rebecca A Marsh, Sergio D Rosenzweig, Jordan S Orange, Roshini S Abraham
The original version of this article unfortunately contained mistakes in some of the author names and affiliations. The correct list of author names and affiliations is below, with the corrections in bold.
May 21, 2018: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29752313/schistosomiasis-induces-persistent-dna-methylation-and-tuberculosis-specific-immune-changes
#2
Andrew R DiNardo, Tomoki Nishiguchi, Emily M Mace, Kimal Rajapakshe, Godwin Mtetwa, Alexander Kay, Gugu Maphalala, W Evan Secor, Rojelio Mejia, Jordan S Orange, Cristian Coarfa, Kapil N Bhalla, Edward A Graviss, Anna M Mandalakas, George Makedonas
Epigenetic mechanisms, such as DNA methylation, determine immune cell phenotype. To understand the epigenetic alterations induced by helminth coinfections, we evaluated the longitudinal effect of ascariasis and schistosomiasis infection on CD4+ T cell DNA methylation and the downstream tuberculosis (TB)-specific and bacillus Calmette-Guérin-induced immune phenotype. All experiments were performed on human primary immune cells from a longitudinal cohort of recently TB-exposed children. Compared with age-matched uninfected controls, children with active Schistosoma haematobium and Ascaris lumbricoides infection had 751 differentially DNA-methylated genes, with 72% hypermethylated...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29744770/global-report-on-primary-immunodeficiencies-2018-update-from-the-jeffrey-modell-centers-network-on-disease-classification-regional-trends-treatment-modalities-and-physician-reported-outcomes
#3
Vicki Modell, Jordan S Orange, Jessica Quinn, Fred Modell
Primary immunodeficiencies (PI) are genetic defects of the immune system that result in chronic, serious, and often life-threatening infections, if not diagnosed and treated. Many patients with PI are undiagnosed, underdiagnosed, or misdiagnosed. In fact, recent studies have shown that PI may be more common than previously estimated and that as many as 1% of the population may be affected with a PI when all types and varieties are considered. In order to raise awareness of PI with the overall goal of reducing associated morbidity and mortality, the Jeffrey Modell Foundation (JMF) established a network of specialized centers that could better identify, diagnose, treat, and follow patients with PI disorders...
May 9, 2018: Immunologic Research
https://www.readbyqxmd.com/read/29694889/pro-inflammation-associated-with-a-gain-of-function-mutation-r284s-in-the-innate-immune-sensor-sting
#4
Hiroyasu Konno, Ivan K Chinn, Diana Hong, Jordan S Orange, James R Lupski, Alejandra Mendoza, Luis A Pedroza, Glen N Barber
The cellular sensor stimulator of interferon genes (STING) initiates type I interferon (IFN) and cytokine production following association with cyclic dinucleotides (CDNs) generated from intracellular bacteria or via a cellular synthase, cGAS, after binding microbial or self-DNA. Although essential for protecting the host against infection, unscheduled STING signaling is now known to be responsible for a variety of autoinflammatory disorders. Here, we report a gain-of-function mutation in STING (R284S), isolated from a patient who did not require CDNs to augment activity and who manifested a constitutively active phenotype...
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29675737/use-of-genetic-testing-for-primary-immunodeficiency-patients
#5
Jennifer R Heimall, David Hagin, Joud Hajjar, Sarah E Henrickson, Hillary S Hernandez-Trujillo, Yuval Tan, Lisa Kobrynski, Kenneth Paris, Troy R Torgerson, James W Verbsky, Richard L Wasserman, Elena W Y Hsieh, Jack J Blessing, Janet S Chou, Monica G Lawrence, Rebecca A Marsh, Sergio D Rosenzweig, Jordan S Orange, Roshini S Abraham
Genetic testing plays a critical role in diagnosis for many primary immunodeficiency diseases. The goals of this report are to outline some of the challenges that clinical immunologists face routinely in the use of genetic testing for patient care. In addition, we provide a review of the types of genetic testing used in the diagnosis of PID, including their strengths and limitations. We describe the strengths and limitations of different genetic testing approaches for specific clinical contexts that raise concern for specific PID disorders in light of the challenges reported by the clinical immunologist members of the CIS in a recent membership survey...
April 19, 2018: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29666621/the-role-of-aire-in-the-immunity-against-candida-albicans-in-a-model-of-human-macrophages
#6
Jose Antonio Tavares de Albuquerque, Pinaki Prosad Banerjee, Angela Castoldi, Royce Ma, Nuria Bengala Zurro, Leandro Hideki Ynoue, Christina Arslanian, Marina Uchoa Wall Barbosa-Carvalho, Joya Emilie de Menezes Correia-Deur, Fernanda Guimarães Weiler, Magnus Regios Dias-da-Silva, Marise Lazaretti-Castro, Luis Alberto Pedroza, Niels Olsen Saraiva Câmara, Emily Mace, Jordan Scott Orange, Antonio Condino-Neto
Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a primary immunodeficiency caused by mutations in the autoimmune regulator gene ( AIRE ). Patients with AIRE mutations are susceptible to Candida albicans infection and present with autoimmune disorders. We previously demonstrated that cytoplasmic AIRE regulates the Syk-dependent Dectin-1 pathway. In this study, we further evaluated direct contact with fungal elements, synapse formation, and the response of macrophage-like THP-1 cells to C...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29592963/single-degranulations-in-nk-cells-can-mediate-target-cell-killing
#7
Lavesh A Gwalani, Jordan S Orange
NK cells are cytotoxic lymphocytes important in defense against viral infection and cancer. NK cells mediate cytotoxicity predominantly through directed secretion of lytic granules, which are specialized lysosome-related organelles, containing effector molecules such as perforin and granzymes. Although many requirements for lytic granule transport to, and secretion at, the NK cell lytic synapse are known, the minimum number of degranulation events required by an NK cell to kill its target is unknown. We performed high-resolution four-dimensional confocal microscopy of human NK-target cell conjugates to quantify NK cell degranulation (using a degranulation indicator, LAMP-1-pHluorin) as well as target cell death...
March 28, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29576764/corrigendum-specific-antibody-deficiency-controversies-in-diagnosis-and-management
#8
Elena Perez, Francisco A Bonilla, Jordan S Orange, Mark Ballow
[This corrects the article on p. 586 in vol. 8, PMID: 28588580.].
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29553488/the-value-of-food-allergy-prevention-in-clinical-practice-in-pediatrics-targeting-early-life
#9
Katherine Anagnostou, Jordan Scott Orange
Food allergies are common and increasing in prevalence, representing a major health concern in many countries around the world. In an effort to diminish the burden of food allergy, many research studies have focused on prevention, and recent findings have revolutionized the way we introduce allergenic foods in early life. We discuss the role of early allergenic food introduction and the value of food allergy prevention in this manuscript.
January 23, 2018: Children
https://www.readbyqxmd.com/read/29398219/nanoscale-dynamism-of-actin-enables-secretory-function-in-cytolytic-cells
#10
Alexandre F Carisey, Emily M Mace, Mezida B Saeed, Daniel M Davis, Jordan S Orange
Natural killer (NK) cells are innate immune effectors that lyse virally infected and tumorigenic cells through the formation of an immunological synapse. Actin remodeling at the lytic immunological synapse is a critical requirement for multiple facets of cytotoxic function. Activating receptor and integrin signaling leads to the regulated turnover and remodeling of actin, which is required for adhesion, sustained receptor signaling, and ultimately exocytosis. NK cells undergo lytic granule exocytosis in hypodense regions of a pervasive actin network...
February 19, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29394140/effect-of-sonic-resin-composite-delivery-on-void-formation-assessed-by-micro-computed-tomography
#11
R Hirata, R R Pacheco, E Caceres, M N Janal, M F Romero, M Giannini, P G Coelho, F A Rueggeberg
OBJECTIVES: The aim of this study was to quantify the internal void volume formation in commercially available, resin composites inserted using conventional or sonic insertion methods, and analyzed using three-dimensional (3D) micro-computed tomography (μCT). METHODS AND MATERIALS: Four resin composites were evaluated: one conventional (Herculite, Ultra, Kerr Corporation, Orange, CA, USA), one flowable bulk fill (SureFil SDR Flow, Dentsply International, York, PA, USA), and two packable bulk fill (SonicFill, Kerr Corporation, and Tetric EvoCeram Bulk Fill, Ivoclar Vivadent Inc, Schaan, Liechtenstein)...
March 2018: Operative Dentistry
https://www.readbyqxmd.com/read/29330011/mutations-in-pi3k110%C3%AE-cause-impaired-natural-killer-cell-function-partially-rescued-by-rapamycin-treatment
#12
Raquel Ruiz-García, Alexander Vargas-Hernández, Ivan K Chinn, Laura S Angelo, Tram N Cao, Zeynep Coban-Akdemir, Shalini N Jhangiani, Qingchang Meng, Lisa R Forbes, Donna M Muzny, Luis M Allende, Mohammed S Ehlayel, Richard A Gibbs, James R Lupski, Gulbu Uzel, Jordan S Orange, Emily M Mace
BACKGROUND: Heterozygous gain-of-function mutations in PI3K110δ lead to lymphadenopathy, lymphoid hyperplasia, EBV and cytomegalovirus viremia, and sinopulmonary infections. OBJECTIVE: The known role of natural killer (NK) cell function in the control of EBV and cytomegalovirus prompted us to investigate the functional and phenotypic effects of PI3K110δ mutations on NK cell subsets and cytotoxic function. METHODS: Mutations in patients were identified by using whole-exome or targeted sequencing...
January 10, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29296090/clinical-and-economic-outcomes-of-a-high-touch-clinical-management-program-for-intravenous-immunoglobulin-therapy
#13
Julia Zhu, Heather S Kirkham, Gretchen Ayer, Chi-Chang Chen, Rolin L Wade, Swapna U Karkare, Chester H Robson, Jordan S Orange
Objective: To compare clinical and economic outcomes of patients who received intravenous immunoglobulin (IVIG) therapies and were managed by a clinical management program vs the outcomes of matched controls using administrative claim data. Methods: This retrospective cohort study used the PharMetrics Plus™ claim database between September 1, 2011 and June 30, 2014. Patients in the intervention group were from a "high-touch" IVIG clinical management program administered by a home infusion specialty pharmacy...
2018: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/29196075/outcomes-after-allogeneic-transplant-in-patients-with-wiskott-aldrich-syndrome
#14
Alexander Ngwube, I Celine Hanson, Jordan Orange, Nicholas L Rider, Filiz Seeborg, William Shearer, Lenora Noroski, Sarah Nicholas, Lisa Forbes, Kathryn Leung, Ghadir Sasa, Swati Naik, Meenakshi Hegde, Bilal Omer, Nabil Ahmed, Carl Allen, Stephen Gottschalk, Meng-Fen Wu, Hao Liu, Malcolm Brenner, Helen Heslop, Robert Krance, Caridad Martinez
Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by a triad of immunodeficiency, eczema, and thrombocytopenia. Currently, hematopoietic stem cell transplantation (HSCT) is the most reliable curative treatment with excellent results for patients with HLA-matched family or unrelated donors. However, even after fully myeloablative preparative regimens, mixed donor chimerism is a potential concern. We performed a retrospective chart review of 12 children who underwent allogeneic HSCT for WAS to report our experience...
March 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29111217/ruxolitinib-partially-reverses-functional-natural-killer-cell-deficiency-in-patients-with-signal-transducer-and-activator-of-transcription-1-stat1-gain-of-function-mutations
#15
Alexander Vargas-Hernández, Emily M Mace, Ofer Zimmerman, Christa S Zerbe, Alexandra F Freeman, Sergio Rosenzweig, Jennifer W Leiding, Troy Torgerson, Matthew C Altman, Edith Schussler, Charlotte Cunningham-Rundles, Ivan K Chinn, Alexandre F Carisey, Imelda C Hanson, Nicholas L Rider, Steven M Holland, Jordan S Orange, Lisa R Forbes
BACKGROUND: Natural killer (NK) cells are critical innate effector cells whose development is dependent on the Janus kinase-signal transducer and activator of transcription (STAT) pathway. NK cell deficiency can result in severe or refractory viral infections. Patients with STAT1 gain-of-function (GOF) mutations have increased viral susceptibility. OBJECTIVE: We sought to investigate NK cell function in patients with STAT1 GOF mutations. METHODS: NK cell phenotype and function were determined in 16 patients with STAT1 GOF mutations...
October 27, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29093717/editorial-nk-cell-subsets-in-health-and-disease-new-developments
#16
EDITORIAL
Emanuela Marcenaro, Luigi D Notarangelo, Jordan S Orange, Eric Vivier
No abstract text is available yet for this article.
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29079655/reversible-transgene-expression-reduces-fratricide-and-permits-4-1bb-costimulation-of-car-t-cells-directed-to-t-cell-malignancies
#17
Maksim Mamonkin, Malini Mukherjee, Madhuwanti Srinivasan, Sandhya Sharma, Diogo Gomes-Silva, Feiyan Mo, Giedre Krenciute, Jordan S Orange, Malcolm K Brenner
T cells expressing second-generation chimeric antigen receptors (CARs) specific for CD5, a T-cell surface marker present on normal and malignant T cells, can selectively kill tumor cells. We aimed to improve this killing by substituting the CD28 costimulatory endodomain (28.z) with 4-1BB (BB.z), as 28.z CD5 CAR T cells rapidly differentiated into short-lived effector cells. In contrast, 4-1BB costimulation is known to promote development of the central memory subpopulation. Here, we found BB.z CD5 CAR T cells had impaired growth compared with 28...
January 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29079582/c-mpl-provides-tumor-targeted-t-cell-receptor-transgenic-t-cells-with-costimulation-and-cytokine-signals
#18
Christopher D Nishimura, Daniel A Brenner, Malini Mukherjee, Rachel A Hirsch, Leah Ott, Meng-Fen Wu, Hao Liu, Olga Dakhova, Jordan S Orange, Malcolm K Brenner, Charles Y Lin, Caroline Arber
Adoptively transferred T-cell receptor (TCR)-engineered T cells depend on host-derived costimulation and cytokine signals for their full and sustained activation. However, in patients with cancer, both signals are frequently impaired. Hence, we developed a novel strategy that combines both essential signals in 1 transgene by expressing the nonlymphoid hematopoietic growth factor receptor c-MPL (myeloproliferative leukemia), the receptor for thrombopoietin (TPO), in T cells. c-MPL signaling activates pathways shared with conventional costimulatory and cytokine receptor signaling...
December 21, 2017: Blood
https://www.readbyqxmd.com/read/29054706/quality-of-life-for-parents-of-children-with-food-allergy-in-peanut-restricted-versus-peanut-free-schools-in-the-united-states-and-canada
#19
Dipika R Patel, Julia E M Upton, Julie Wang, Laurie Harada, Danielle Guffey, Charles G Minard, Jordan Orange, Carla M Davis
No abstract text is available yet for this article.
March 2018: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29016929/trivalent-car-t-cells-overcome-interpatient-antigenic-variability-in-glioblastoma
#20
Kevin Bielamowicz, Kristen Fousek, Tiara T Byrd, Hebatalla Samaha, Malini Mukherjee, Nikita Aware, Meng-Fen Wu, Jordan S Orange, Pavel Sumazin, Tsz-Kwong Man, Sujith K Joseph, Meenakshi Hegde, Nabil Ahmed
Background: Glioblastoma (GBM) is the most common primary malignant brain cancer, and is currently incurable. Chimeric antigen receptor (CAR) T cells have shown promise in GBM treatment. While we have shown that combinatorial targeting of 2 glioma antigens offsets antigen escape and enhances T-cell effector functions, the interpatient variability in surface antigen expression between patients hinders the clinical impact of targeting 2 antigen pairs. This study addresses targeting 3 antigens using a single CAR T-cell product for broader application...
March 27, 2018: Neuro-oncology
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