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Clinical Immunology: the Official Journal of the Clinical Immunology Society

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https://www.readbyqxmd.com/read/28720549/evolutionary-basis-of-a-new-approach-for-the-treatment-of-malignant-brain-tumors-from-mice-to-humans
#1
Pedro R Lowenstein, Maria G Castro
Glioma cells are one of the most aggressive and malignant tumors. Following initial surgery, and radio-chemotherapy they progress rapidly, so that patients' median survival remains under two years. They invade throughout the brain, which makes them difficult to treat, and are universally lethal. Though total resection is always attempted it is not curative. Standard of care in 2016 comprises surgical resection, radiotherapy and chemotherapy (temozolomide). Median survival is currently ~14-20months post-diagnosis though it can be higher in high complexity medical university centers, or during clinical trials...
July 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28709914/the-ratio-of-circulating-follicular-t-helper-cell-to-follicular-t-regulatory-cell-is-correlated-with-disease-activity-in-systemic-lupus-erythematosus
#2
Bihua Xu, Shuang Wang, Mianjing Zhou, Yuefang Huang, Rong Fu, Chaohuan Guo, Jingxian Chen, Jijun Zhao, Felicia Gaskin, Shu Man Fu, Niansheng Yang
Follicular T regulatory (Tfr) cells inhibit follicular T helper (Tfh) cells mediated B cell responses. Tfh cells are involved in the pathogenesis of systemic lupus erythematosus (SLE). However, the role of Tfr cells in SLE remains unclear. The frequency of circulating Tfr and Tfh cells were examined in SLE patients and healthy controls. The frequency of circulating Tfr cell decreased and Tfh/Tfr ratio increased in SLE patients. Serum anti-dsDNA antibody level positively correlated with frequency of Tfh cells and Tfh/Tfr ratios but negatively correlated with the frequency of Tfr cells...
July 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28705765/terminal-14q32-33-deletion-as-a-novel-cause-of-agammaglobulinemia
#3
Christoph B Geier, Alexander Piller, Martha M Eibl, Peter Ciznar, Denisa Ilencikova, Hermann M Wolf
Over the past decades, a pleiotropic spectrum of B-cell intrinsic defects leading to early onset agammaglobulinemia and absent B cells has been described. Herein we report terminal 14q32.33 deletion as a novel cause of agammaglobulinemia. We describe a 20-year old man with a 1MB terminal 14q32.33 deletion resulting in a loss of the entire Immunoglobulin heavy chain gene region of chromosome 14. The patient presented with absent serum immunoglobulins levels and absent circulating B cells since age 2. The clinical picture was dominated by severe episodes of recurrent upper respiratory tract infections...
July 10, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28694137/idiopathic-t-cell-lymphopenia-identified-in-new-york-state-newborn-screening
#4
Stephanie Albin-Leeds, Juliana Ochoa, Harshna Mehta, Beth H Vogel, Michele Caggana, Vincent Bonagura, Heather Lehman, Mark Ballow, Arye Rubinstein, Subhadra Siegel, Leonard Weiner, Geoffrey A Weinberg, Charlotte Cunningham-Rundles
Quantification of T-cell receptor excision circles (TRECs) for newborn screening for SCID has advanced the diagnosis of severe combined immune deficiency (SCID). However, it has led to the identification of infants with T cell lymphopenia without known cause. The clinical characteristics, appropriate laboratory monitoring, and outcomes of patients remain unclear. We performed a retrospective review of clinical and laboratory studies for 26 infants collected from 7 New York State referral centers from 2010 to 2016 with low TRECs (mean, 70copies/μl) and subnormal CD3 counts (mean, 1150/cubicmm)...
July 7, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28689783/immune-complexes-containing-malondialdehyde-mda-ldl-induce-apoptosis-in-human-macrophages
#5
Gabriel Virella, Kelsey Wilson, Johnathon Elkes, Samar M Hammad, Hussein A Rajab, Yanchun Li, Charlyne Chassereau, Yan Huang, Maria Lopes-Virella
Immune complexes (IC) containing predominantly malondialdehyde-LDL and the corresponding autoantibodies (MDA-LDL IC) predict acute cardiovascular events, while IC rich in oxidized LDL (oxLDL IC) predict cardiovascular disease progression. Our objective was to determine mechanisms that could explain these prognostic differences. We compared the effects of the interaction of oxLDL, MDA-LDL and the corresponding IC with human macrophages focusing on apoptosis, metalloproteinases, and proinflammatory cytokines...
July 6, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28689782/the-microbiota-and-autoimmunity-their-role-in-thyroid-autoimmune-diseases
#6
REVIEW
Hedda L Köhling, Sue F Plummer, Julian R Marchesi, Kelly S Davidge, Marian Ludgate
Since the 1970s, the role of infectious diseases in the pathogenesis of Graves' disease (GD) has been an object of intensive research. The last decade has witnessed many studies on Yersinia enterocolitica, Helicobacter pylori and other bacterial organisms and their potential impact on GD. Retrospective, prospective and molecular binding studies have been performed with contrary outcomes. Until now it is not clear whether bacterial infections can trigger autoimmune thyroid disease. Common risk factors for GD (gender, smoking, stress, and pregnancy) reveal profound changes in the bacterial communities of the gut compared to that of healthy controls but a pathogenetic link between GD and dysbiosis has not yet been fully elucidated...
July 6, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28673862/sjogren-s-syndrome-new-paradigms-and-areas-for-future-research
#7
Julian L Ambrus
No abstract text is available yet for this article.
June 30, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28668589/rare-splicing-defects-of-fas-underly-severe-recessive-autoimmune-lymphoproliferative-syndrome
#8
N Agrebi, I Ben-Mustapha, N Matoussi, N Dhouib, M Ben-Ali, N Mekki, M Ben-Ahmed, B Larguèche, S Ben Becher, M Béjaoui, M R Barbouche
Autoimmune lymphoproliferative syndrome (ALPS) is a prototypic disorder of impaired apoptosis characterized by autoimmune features and lymphoproliferation. Heterozygous germline or somatic FAS mutations associated with preserved protein expression have been described. Very rare cases of homozygous germline FAS mutations causing severe autosomal recessive form of ALPS with a complete defect of Fas expression have been reported. We report two unrelated patients from highly inbred North African population showing a severe ALPS phenotype and an undetectable Fas surface expression...
June 29, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28648633/identification-of-evidence-for-autoimmune-pathology-of-bilateral-sudden-sensorineural-hearing-loss-using-proteomic-analysis
#9
Jeon Mi Lee, Jin Young Kim, Jinwoong Bok, Kyu-Sung Kim, Jae Young Choi, Sung Huhn Kim
Sudden sensorineural hearing loss (S-SNHL) is an inner ear disorder with an abrupt hearing loss occurring <3days. The pathologic mechanism of the disease remains unclear, although autoimmunity has been regarded as one of the suggested causes, especially in bilateral form. In this study, we aimed to provide evidence for the involvement of autoimmunity in bilateral S-SNHL using proteomic approaches such as ProtoArray®, western blotting, immunoprecipitation, and liquid column mass spectrometry for mass screening of candidate antigens and autoantibodies based on the hypothesis that multiple autoantibodies and target antigens must exist in order for autoimmune bilateral S-SNHL to develop...
June 22, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28647502/alternative-complement-pathway-hemolytic-assays-reveal-incomplete-complement-blockade-in-patients-treated-with-eculizumab
#10
Bénédicte Puissant-Lubrano, Sylvain Puissochet, Nicolas Congy-Jolivet, Dominique Chauveau, Stéphane Decramer, Arnaud Garnier, Antoine Huart, Nassim Kamar, David Ribes, Antoine Blancher
Eculizumab is a monoclonal anti-C5 antibody used in the treatment of atypical hemolytic uremic syndrome (aHUS). We monitored complement inhibition in 16 eculizumab-treated patients suffering from HUS or transplant rejection (not aHUS patients). Blood samples were obtained one to four weeks after the last eculizumab injection. We observed that eculizumab efficiently blocked the terminal pathway (TP) through classical pathway (CP) activation measured by kinetic hemolytic assay (HA) (<10%) but incompletely blocked the TP through alternative pathway (AP) activation measured by rabbit (APH50>23%) or chicken erythrocytes HA (AP100>15%)...
June 21, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28645875/high-resolution-igh-repertoire-analysis-reveals-fetal-liver-as-the-likely-origin-of-life-long-innate-b-lymphopoiesis-in-humans
#11
Anindita Roy, Vojtech Bystry, Georg Bohn, Katerina Goudevenou, Tomas Reigl, Maria Papaioannou, Adam Krejci, Sorcha O'Byrne, Aristeidis Chaidos, Andrea Grioni, Nikos Darzentas, Irene A G Roberts, Anastasios Karadimitris
The ontogeny of the natural, public IgM repertoire remains incompletely explored. Here, high-resolution immunogenetic analysis of B cells from (unrelated) fetal, child, and adult samples, shows that although fetal liver (FL) and bone marrow (FBM) IgM repertoires are equally diversified, FL is the main source of IgM natural immunity during the 2nd trimester. Strikingly, 0.25% of all prenatal clonotypes, comprising 18.7% of the expressed repertoire, are shared with the postnatal samples, consistent with persisting fetal IgM+ B cells being a source of natural IgM repertoire in adult life...
June 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28642148/biological-activity-of-glatiramer-acetate-on-treg-and-anti-inflammatory-monocytes-persists-for-more-than-10years-in-responder-multiple-sclerosis-patients
#12
Michela Spadaro, Francesca Montarolo, Simona Perga, Serena Martire, Federica Brescia, Simona Malucchi, Antonio Bertolotto
Glatiramer acetate (GA) is a widely used treatment for multiple sclerosis (MS), with incompletely defined mechanism of action. Short-term studies suggested its involvement in the modulation of anti-inflammatory cytokines and regulatory T cells (Treg), while long-term effect is still unknown. To investigate this aspect, we analyzed by flow-cytometry peripheral-blood Treg, natural killer (NK), CD4 and CD8 T-cells and anti-inflammatory CD14(+)CD163(+) monocytes from 37 healthy donor and 90 RRMS patients divided in untreated, treated with GA for 12months and from 34 to 192months...
June 19, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28625885/dock8-deficiency-insights-into-pathophysiology-clinical-features-and-management
#13
REVIEW
Catherine M Biggs, Sevgi Keles, Talal A Chatila
Dedicator of cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency that exemplifies the broad clinical features of primary immunodeficiencies (PIDs), extending beyond recurrent infections to include atopy, autoimmunity and cancer. It is caused by loss of function mutations in DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes that regulates the actin cytoskeleton. Additional roles of DOCK8 have also emerged, including regulating MyD88-dependent Toll-like receptor signaling and the activation of the transcription factor STAT3...
June 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28625884/lack-of-evidence-for-post-vaccine-onset-of-autoimmune-lymphoproliferative-disorders-during-a-nine-month-follow-up-in-multiply-vaccinated-italian-military-personnel
#14
Claudia Ferlito, Vincenzo Barnaba, Sergio Abrignani, Mauro Bombaci, Alessandro Sette, John Sidney, Roberto Biselli, Enrico Tomao, Maria Sofia Cattaruzza, Valentina Germano, Michela Ileen Biondo, Gerardo Salerno, Patrizia Lulli, Sara Caporuscio, Andrea Picchianti Diamanti, Mirella Falco, Valentina Biselli, Patrizia Cardelli, Alberto Autore, Elena Lucertini, Donato Pompeo De Cesare, Mario Stefano Peragallo, Florigio Lista, Carmela Martire, Simonetta Salemi, Roberto Nisini, Raffaele D'Amelio
Anecdotal case reports, amplified by mass media and internet-based opinion groups, have recently indicated vaccinations as possibly responsible for autoimmunity/lymphoproliferation development. Multiply vaccinated Italian military personnel (group 1, operating in Italy, group 2, operating in Lebanon) were followed-up for nine months to monitor possible post-vaccine autoimmunity/lymphoproliferation onset. No serious adverse event was noticed in both groups. Multivariate analysis of intergroup differences only showed a significant association between lymphocyte increase and tetanus/diphtheria vaccine administration...
June 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28625883/tcr-cd3-cd4-cd8-effector-t-cells-in-psoriasis
#15
D Brandt, M Sergon, S Abraham, K Mäbert, C M Hedrich
The autoimmune/inflammatory disorder psoriasis is characterized by keratinocyte proliferation and immune cell infiltration of the skin. TCR(+)CD3(+)CD4(-)CD8(-) "double negative" (DN) T cells can derive from CD8(+) T cells through the down-regulation of CD8. The inhibitory molecule programmed death (PD-)1 is expressed on activated T cells and plays a role in the maintenance of peripheral tolerance. A subset of DN T cells, characterized by the expression of PD-1, has recently been demonstrated to be self-reactive...
June 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28579554/stat3-gain-of-function-mutations-associated-with-autoimmune-lymphoproliferative-syndrome-like-disease-deregulate-lymphocyte-apoptosis-and-can-be-targeted-by-bh3-mimetic-compounds
#16
Schafiq Nabhani, Cyrill Schipp, Hagit Miskin, Carina Levin, Sergey Postovsky, Tal Dujovny, Ariel Koren, Dan Harlev, Anne-Marie Bis, Franziska Auer, Baerbel Keller, Klaus Warnatz, Michael Gombert, Sebastian Ginzel, Arndt Borkhardt, Polina Stepensky, Ute Fischer
Autoimmune lymphoproliferative syndrome (ALPS) is typically caused by mutations in genes of the extrinsic FAS mediated apoptotic pathway, but for about 30% of ALPS-like patients the genetic diagnosis is lacking. We analyzed 30 children with ALPS-like disease of unknown cause and identified two dominant gain-of-function mutations of the Signal Transducer And Activator Of Transcription 3 (STAT3, p.R278H, p.M394T) leading to increased transcriptional activity. Hyperactivity of STAT3, a known repressor of FAS, was associated with decreased FAS-mediated apoptosis, mimicking ALPS caused by FAS mutations...
June 1, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28578025/multimarker-risk-stratification-approach-at-multiple-sclerosis-onset
#17
Lidia Fernández-Paredes, Armanda Casrouge, Jérémie Decalf, Clara de Andrés, Luisa Maria Villar, Rebeca Pérez de Diego, Bárbara Alonso, José Carlos Álvarez Cermeño, Rafael Arroyo, Marta Tejera-Alhambra, Joaquín Navarro, Celia Oreja-Guevara, Margarita López Trascasa, Ansgar Seyfferth, Maria Angel García Martínez, Roberto Álvarez Lafuente, Matthew L Albert, Silvia Sánchez-Ramón
Delay in the diagnosis of multiple sclerosis (MS) stems from the lack of specific clinical and analytical markers to assist in the early diagnosis and prediction of progressive course. We propose a decision-tree model that better defines early at onset MS patients and those with the progressive form by analysing a 12-biomarkers panel in serum and CSF samples of patients with MS, other neurological diseases (OND) and healthy contols. Thus, patients at onset of neurological disease were first classified by serum IL-7 levels <141pg/ml (OR=6...
May 31, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28578024/hexamerization-enhanced-cd20-antibody-mediates-complement-dependent-cytotoxicity-in-serum-genetically-deficient-in-c9
#18
Ronald P Taylor, Margaret A Lindorfer, Erika M Cook, Frank J Beurskens, Janine Schuurman, Paul W H I Parren, Clive S Zent, Karl R VanDerMeid, Richard Burack, Masashi Mizuno, B Paul Morgan
We examined complement-dependent cytotoxicity (CDC) by hexamer formation-enhanced CD20 mAb Hx-7D8 of patient-derived chronic lymphocytic leukemia (CLL) cells that are relatively resistant to CDC. CDC was analyzed in normal human serum (NHS) and serum from an individual genetically deficient for C9. Hx-7D8 was able to kill up to 80% of CLL cells in complete absence of C9. We conclude that the narrow C5b-8 pores formed without C9 are sufficient for CDC due to efficient antibody-mediated hexamer formation. In the absence of C9, we observed transient intracellular increases of Ca(2+) during CDC (as assessed with FLUO-4) that were extended in time...
May 31, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28578023/a-novel-germline-gain-of-function-variant-in-pik3cd
#19
LETTER
William Rae, Yifang Gao, Daniel Ward, Christopher J Mattocks, Efrem Eren, Anthony P Williams
No abstract text is available yet for this article.
May 31, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28552470/cd4-t-cells-from-hiv-1-patients-with-impaired-th1-effector-responses-to-mycobacterium-tuberculosis-exhibit-diminished-histone-and-nucleoprotein-signatures
#20
Lillian Seu, James A Mobley, Paul A Goepfert
HIV+ patients have an increased risk for tuberculosis disease despite clinical management with ARTs. We established a culture model of Mtb-infection in PBMCs from HIV+ PPD+ donors on suppressive ART (median 6.4years) with negligible viral loads (median<50copies/mL) and stable CD4+ T cell counts (517cells/mm^3). We observed that HIV+ patient lymphocytes harbored a recruitment defect to Mtb-infected monocytes. To investigate these immune defects on a per cell basis, purified CD4+ T cells from HIV patients were assessed by label-free quantification protein mass spectrometry...
May 25, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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