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https://www.readbyqxmd.com/read/27909225/recovery-of-the-immune-system-after-exercise
#1
Jonathan M Peake, Oliver Neubauer, Neil P Walsh, Richard J Simpson
The notion that prolonged, intense exercise causes an 'open window' of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts, and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions (e...
December 1, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27895164/mysm1-dependent-checkpoints-in-b-cell-lineage-differentiation-and-b-cell-mediated-immune-response
#2
Michael Förster, Kyo Farrington, Jessica C Petrov, Jad I Belle, Barbara C Mindt, Mariko Witalis, Claudia U Duerr, Jörg H Fritz, Anastasia Nijnik
MYSM1 is a chromatin-binding histone deubiquitinase. MYSM1 mutations in humans result in lymphopenia whereas loss of Mysm1 in mice causes severe hematopoietic abnormalities, including an early arrest in B cell development. However, it remains unknown whether MYSM1 is required at later checkpoints in B cell development or for B cell-mediated immune responses. We analyzed conditional mouse models Mysm1(fl/fl)Tg.mb1-cre, Mysm1(fl/fl)Tg.CD19-cre, and Mysm1(fl/fl)Tg.CD21-cre with inactivation of Mysm1 at prepro-B, pre-B, and follicular B cell stages of development...
November 28, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27884168/ataxia-telangiectasia-a-review
#3
REVIEW
Cynthia Rothblum-Oviatt, Jennifer Wright, Maureen A Lefton-Greif, Sharon A McGrath-Morrow, Thomas O Crawford, Howard M Lederman
DEFINITION OF THE DISEASE: Ataxia telangiectasia (A-T) is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome. EPIDEMIOLOGY: The world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births. CLINICAL DESCRIPTION: A-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages...
November 25, 2016: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/27879260/antibiotics-impair-murine-hematopoiesis-by-depleting-intestinal-microbiota
#4
Kamilla S Josefsdottir, Megan T Baldridge, Claudine S Kadmon, Katherine Y King
Bone marrow suppression is an adverse effect associated with many antibiotics, especially when administered for prolonged treatment courses. Recent advances in our understanding of steady-state hematopoiesis have allowed us to explore the effects of antibiotics on hematopoietic progenitors in detail using a murine model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia, with pronounced pan-lymphopenia as demonstrated by flow cytometric analysis of peripheral blood. Bone marrow progenitor analysis revealed depletion of hematopoietic stem cells and multipotent progenitors across all subtypes...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27873105/newborn-screening-for-severe-primary-immunodeficiency-diseases-in-sweden-a-2-year-pilot-trec-and-krec-screening-study
#5
Michela Barbaro, Annika Ohlsson, Stephan Borte, Susanne Jonsson, Rolf H Zetterström, Jovanka King, Jacek Winiarski, Ulrika von Döbeln, Lennart Hammarström
Newborn screening for severe primary immunodeficiencies (PID), characterized by T and/or B cell lymphopenia, was carried out in a pilot program in the Stockholm County, Sweden, over a 2-year period, encompassing 58,834 children. T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) were measured simultaneously using a quantitative PCR-based method on DNA extracted from dried blood spots (DBS), with beta-actin serving as a quality control for DNA quantity. Diagnostic cutoff levels enabling identification of newborns with milder and reversible T and/or B cell lymphopenia were also evaluated...
November 21, 2016: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27803128/stat-mutations-as-program-switchers-turning-primary-immunodeficiencies-into-autoimmune-diseases
#6
REVIEW
Tiziana Lorenzini, Laura Dotta, Mauro Giacomelli, Donatella Vairo, Raffaele Badolato
STAT proteins are a family of transcription factors that mediate cellular response to cytokines and growth factors. Study of patients with familial susceptibility to pathogens and/or autoimmune diseases has led to the identification of 7 inherited disorders that are caused by mutations of 4 STAT family genes. Homozygous or compound heterozygous mutations of STAT1 lead to complete or partial forms of STAT1 deficiency that are associated with susceptibility to intracellular pathogens and herpetic infections. Patients with heterozygous STAT1 gain-of-function (GOF) mutations usually present with chronic mucocutaneous candidiasis (CMC) but may also experience bacterial and viral infections, autoimmune manifestations, lymphopenia, cerebral aneurysms, and increased risk to develop tumors...
November 1, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27734333/a-novel-mutation-in-a-critical-region-for-the-methyl-donor-binding-in-dnmt3b-causes-immunodeficiency-centromeric-instability-and-facial-anomalies-syndrome-icf
#7
Erez Rechavi, Atar Lev, Eran Eyal, Ortal Barel, Nitzan Kol, Sarit Farage Barhom, Ben Pode-Shakked, Yair Anikster, Raz Somech, Amos J Simon
PURPOSE: Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is an extremely rare autosomal recessive disease. The immune phenotype is characterized by hypogammaglobulinemia in the presence of B cells. T cell lymphopenia also develops in some patients. We sought to further investigate the immune defect in an ICF patient with a novel missense mutation in DNMT3B and a severe phenotype. METHODS: Patient lymphocytes were examined for subset counts, immunoglobulin levels, T and B cell de novo production (via excision circles) and receptor repertoire diversity...
November 2016: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27718204/analysis-of-the-innate-response-to-adjuvants-characterization-of-the-draining-lymph-node-by-fluorescence-activated-cell-sorting
#8
Anthony L Desbien
A clear index for a response to adjuvants is a change in the cellular composition of lymph nodes draining the site of adjuvant injection (Didierlaurent et al., J Immunol 183:6186-6197, 2009; Caproni et al., J Immunol 188:3088-98, 2012; Desbien et al., Eur J Immunol 1-11, 2014). During the steady state, lymph nodes (LNs) are composed of a fixed ratio of innate and adaptive cells awaiting activation signals from tissue draining lymph. Upon exposure to innate stimulants, lymph nodes undergo dramatic changes. The most apparent change to the lymph node is an increase in size...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27707659/precision-molecular-diagnosis-defines-specific-therapy-in-combined-immunodeficiency-with-megaloblastic-anemia-secondary-to-mthfd1-deficiency
#9
Kesava A Ramakrishnan, Reuben J Pengelly, Yifang Gao, Mary Morgan, Sanjay V Patel, E Graham Davies, Sarah Ennis, Saul N Faust, Anthony P Williams
BACKGROUND: Methylenetetrahydrofolate dehydrogenase (MTHFD1) deficiency has recently been reported to cause a folate-responsive syndrome displaying a phenotype that includes megaloblastic anemia and severe combined immunodeficiency. OBJECTIVE: To describe our investigative approach to the molecular diagnosis and evaluation of immune dysfunction in a family with MTHFD1 deficiency. METHODS: The methods used were exome sequencing and analysis of variants in genes involved in the folate metabolic pathway in a family with 2 affected siblings...
October 1, 2016: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/27694827/chemical-chaperone-tudca-prevents-apoptosis-and-improves-survival-during-polymicrobial-sepsis-in-mice
#10
Marcel Doerflinger, Jason Glab, Christina Nedeva, Irvin Jose, Ann Lin, Lorraine O'Reilly, Cody Allison, Marc Pellegrini, Richard S Hotchkiss, Hamsa Puthalakath
Sepsis-induced lymphopenia is a major cause of morbidities in intensive care units and in populations with chronic conditions such as renal failure, diabetes, HIV and alcohol abuse. Currently, other than supportive care and antibiotics, there are no treatments for this condition. We developed an in vitro assay to understand the role of the ER-stress-mediated apoptosis process in lymphocyte death during polymicrobial sepsis, which was reproducible in in vivo mouse models. Modulating ER stress using chemical chaperones significantly reduced the induction of the pro-apoptotic protein Bim both in vitro and in mice...
October 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27683081/modulating-sphingosine-1-phosphate-signaling-with-dop-or-fty720-alleviates-vascular-and-immune-defects-in-mouse-sepsis
#11
Nasr Y A Hemdan, Cynthia Weigel, Christina-Maria Reimann, Markus H Gräler
Sepsis is a systemic inflammatory response to pathogens and a leading cause of hospital related mortality worldwide. Sphingosine 1-phosphate (S1P) regulates multiple cellular processes potentially involved in the pathogenesis of sepsis, including antigen presentation, lymphocyte egress, and maintenance of vascular integrity. We thus explored the impact of manipulating S1P signaling in experimental polymicrobial sepsis in mice. Administration of 4-deoxypyridoxine (DOP), an inhibitor of the S1P-degrading enzyme S1P-lyase, or of the sphingosine analog FTY720 that serves as an S1P receptor agonist after phosphorylation ameliorated morbidity, improved recovery from sepsis in surviving mice, and reduced sepsis-elicited hypothermia and body weight loss...
September 29, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27532609/safety-studies-in-tumor-and-non-tumor-bearing-mice-in-support-of-clinical-trials-using-oncolytic-vsv-ifn%C3%AE-nis
#12
Lianwen Zhang, Michael B Steele, Nathan Jenks, Jacquelyn Grell, Lukkana Suksanpaisan, Shruthi Naik, Mark J Federspiel, Martha Q Lacy, Stephen J Russell, Kah-Whye Peng
Oncolytic VSV-IFNβ-NIS is selectively destructive to tumors. Here, we present the IND enabling preclinical rodent studies in support of clinical testing of vesicular stomatitis virus (VSV) as a systemic therapy. Efficacy studies showed dose-dependent tumor regression in C57BL/KaLwRij mice bearing syngeneic 5TGM1 plasmacytomas after systemic VSV administration. In contrast, the virus was effective at all doses tested against human KAS6/1 xenografts in SCID mice. Intravenous administration of VSV-mIFNβ-NIS is well tolerated in C57BL/6 mice up to 5 × 10(10) TCID50 (50% tissue culture infective dose)/kg with no neurovirulence, no cytokine storm, and no abnormalities in tissues...
September 2016: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/27523934/sarcoptic-mange-in-dogs-its-effect-on-liver-oxidative-stress-trace-minerals-and-vitamins
#13
S A Beigh, J S Soodan, A M Bhat
The present study was aimed to determine the effect on liver, associated oxidative stress, trace element and vitamin alteration in dogs with sarcoptic mange. A total of 24 dogs with clinically established diagnosis of sarcoptic mange, divided into two groups, severely infested group (n=9) and mild/moderately infested group (n=15), according to the extent of skin lesions caused by sarcoptic mange and 6 dogs as control group were included in the present study. In comparison to healthy control hemoglobin, PCV, and TEC were significantly (P<0...
August 30, 2016: Veterinary Parasitology
https://www.readbyqxmd.com/read/27519818/sphingosine-1-phosphate-s1p-lyase-inhibition-causes-increased-cardiac-s1p-levels-and-bradycardia-in-rats
#14
Christopher M Harris, Scott Mittelstadt, Patricia Banfor, Peter Bousquet, David B Duignan, Gary Gintant, Michelle Hart, Youngjae Kim, Jason Segreti
Inhibition of the sphingosine-1-phosphate (S1P)-catabolizing enzyme S1P lyase (S1PL) elevates the native ligand of S1P receptors and provides an alternative mechanism for immune suppression to synthetic S1P receptor agonists. S1PL inhibition is reported to preferentially elevate S1P in lymphoid organs. Tissue selectivity could potentially differentiate S1PL inhibitors from S1P receptor agonists, the use of which also results in bradycardia, atrioventricular block, and hypertension. But it is unknown if S1PL inhibition would also modulate cardiac S1P levels or cardiovascular function...
October 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27421731/jc-virus-granule-cell-neuronopathy-in-the-setting-of-chronic-lymphopenia-treated-with-recombinant-interleukin-7
#15
David N Soleimani-Meigooni, Katherine E Schwetye, Maria Reyes Angeles, Caroline F Ryschkewitsch, Eugene O Major, Xin Dang, Igor J Koralnik, Robert E Schmidt, David B Clifford, F Matthew Kuhlmann, Robert C Bucelli
JC virus (JCV) is a human polyomavirus that infects the central nervous system (CNS) of immunocompromised patients. JCV granule cell neuronopathy (JCV-GCN) is caused by infection of cerebellar granule cells, causing ataxia. A 77-year-old man with iatrogenic lymphopenia presented with severe ataxia and was diagnosed with JCV-GCN. His ataxia and cerebrospinal fluid (CSF) improved with intravenous immunoglobulin, high-dose intravenous methylprednisolone, mirtazapine, and mefloquine. Interleukin-7 (IL-7) therapy reconstituted his lymphocytes and reduced his CSF JCV load...
July 15, 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/27405134/cd4-lymphocytopenia-without-hiv-infection
#16
Naporn Khamanarong, Somchai Insiripong
The CD4 lymphocytes are an important part of the immune system. Besides HIV Infection, other conditions can cause a low CD4 count. We report the case of a 82-year-old female who presented with a markedly low CD4 count during a severe lower respiratory tract infection and respiratory failure without HIV infection. The total lymphocyte and the absolute CD4 counts are 255/mm³ and 109/mm³, respectively. Sputum and bronchial lavage fluid were both negative for acid-fast bacilli. The anti-HIV antibody test was negative...
May 2016: Southeast Asian Journal of Tropical Medicine and Public Health
https://www.readbyqxmd.com/read/27317262/sepsis-induced-osteoblast-ablation-causes-immunodeficiency
#17
Asuka Terashima, Kazuo Okamoto, Tomoki Nakashima, Shizuo Akira, Koichi Ikuta, Hiroshi Takayanagi
Sepsis is a host inflammatory response to severe infection associated with high mortality that is caused by lymphopenia-associated immunodeficiency. However, it is unknown how lymphopenia persists after the accelerated lymphocyte apoptosis subsides. Here we show that sepsis rapidly ablated osteoblasts, which reduced the number of common lymphoid progenitors (CLPs). Osteoblast ablation or inducible deletion of interleukin-7 (IL-7) in osteoblasts recapitulated the lymphopenic phenotype together with a lower CLP number without affecting hematopoietic stem cells (HSCs)...
June 21, 2016: Immunity
https://www.readbyqxmd.com/read/27221134/clinical-and-immunologic-phenotype-associated-with-activated-phosphoinositide-3-kinase-%C3%AE-syndrome-2-a%C3%A2-cohort-study
#18
Elodie Elkaim, Benedicte Neven, Julie Bruneau, Kanako Mitsui-Sekinaka, Aurelie Stanislas, Lucie Heurtier, Carrie L Lucas, Helen Matthews, Marie-Céline Deau, Svetlana Sharapova, James Curtis, Janine Reichenbach, Catherine Glastre, David A Parry, Gururaj Arumugakani, Elizabeth McDermott, Sara Sebnem Kilic, Motoi Yamashita, Despina Moshous, Hicham Lamrini, Burkhard Otremba, Andrew Gennery, Tanya Coulter, Isabella Quinti, Jean-Louis Stephan, Vassilios Lougaris, Nicholas Brodszki, Vincent Barlogis, Takaki Asano, Lionel Galicier, David Boutboul, Shigeaki Nonoyama, Andrew Cant, Kohsuke Imai, Capucine Picard, Sergey Nejentsev, Thierry Jo Molina, Michael Lenardo, Sinisa Savic, Marina Cavazzana, Alain Fischer, Anne Durandy, Sven Kracker
BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) 2 (p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency [PASLI]-R1), a recently described primary immunodeficiency, results from autosomal dominant mutations in PIK3R1, the gene encoding the regulatory subunit (p85α, p55α, and p50α) of class IA phosphoinositide 3-kinases. OBJECTIVES: We sought to review the clinical, immunologic, and histopathologic phenotypes of APDS2 in a genetically defined international patient cohort...
July 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27214202/the-impact-of-azathioprine-associated-lymphopenia-on-the-onset-of-opportunistic-infections-in-patients-with-inflammatory-bowel-disease
#19
Marius Vögelin, Luc Biedermann, Pascal Frei, Stephan R Vavricka, Sylvie Scharl, Jonas Zeitz, Michael C Sulz, Michael Fried, Gerhard Rogler, Michael Scharl
BACKGROUND: Thiopurines are known to cause lymphopenia (<1,500 lymphocytes/μl). As severe lymphopenia (<500C/μl) is associated with opportunistic infections, we investigated severity of thiopurine-related lymphopenia and development of opportunistic infections in our tertiary referral centre. METHODS: We retrospectively screened medical records of 1,070 IBD patients and identified 100 individuals that developed a total of 161 episodes of lymphopenia during thiopurine treatment between 2002 and 2014...
2016: PloS One
https://www.readbyqxmd.com/read/27193610/benefit-and-risk-of-tofacitinib-in-the-treatment-of-rheumatoid-arthritis-a-focus-on-herpes-zoster
#20
REVIEW
Kunihiro Yamaoka
The biologics have revolutionized the treatment of rheumatoid arthritis (RA). However, there are still patients that are difficult to control and a cure is still not achievable. Tofacitinib, a Janus kinase (JAK) inhibitor is an orally available, new-in-class, disease-modifying anti-rheumatic drug with similar efficacy to biologics. JAK is activated by multiple cytokines involved in the pathology of RA, and affects non-immune and immune cells, mainly the lymphocytes. Besides its anti-rheumatic effect, the recent focus has been on adverse events...
September 2016: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
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