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Clinical Immunology: the Official Journal of the Clinical Immunology Society

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https://www.readbyqxmd.com/read/28647502/alternative-complement-pathway-hemolytic-assays-reveal-incomplete-complement-blockade-in-patients-treated-with-eculizumab
#1
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-origin-of-life-long-innate-b-lymphopoiesis-in-humans
#2
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/28645874/attenuated-il-2r-signaling-in-cd4-memory-t-cells-of-t1d-subjects-is-intrinsic-and-dependent-on-activation-state
#3
Katharine Schwedhelm, Jerill Thorpe, Sara A Murray, Marc Gavin, Cate Speake, Carla Greenbaum, Karen Cerosaletti, Jane Buckner, S Alice Long
The IL-2/IL-2R pathway is implicated in type 1 diabetes (T1D). While its role in regulatory T cell (Treg) biology is well characterized, mechanisms that influence IL-2 responses in effector T cells (Teff) are less well understood. We compared IL-2 responses in 95 healthy control and 98 T1D subjects. In T1D, low IL-2 responsiveness was most pronounced in memory Teff. Unlike Treg, CD25 expression did not influence the Teff responses. Reduced IL-2 responses in memory Teff were not rescued by resting, remained lower after activation and proliferation, and were absent in type 2 diabetes...
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28536054/effect-of-vitamin-d-replacement-on-immunological-biomarkers-in-patients-with-multiple-sclerosis
#13
May F Mrad, Nabil K El Ayoubi, Maria O Esmerian, Jalal M Kazan, Samia J Khoury
We aimed to investigate the immunologic effects of vitamin D replacement in RRMS patients. In a controlled single center study, patients deficient in 25-hydroxyvitamin D (serum level<25ng/ml) received 10,000IU/week cholecalciferol for 3months. Sufficient vitamin D patients (serum level>35ng/ml) were followed for the same period. Assessments were performed at baseline and at 3months. 25-hydroxyvitamin D levels increased significantly from baseline to month-3 in the deficient group after treatment and remained stable in the sufficient group...
May 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28531376/immune-cell-signaling-in-autoimmune-diseases
#14
REVIEW
George C Tsokos, Noel R Rose
On September 20, 2016 the American Autoimmune Related Disease Association convened a selected group of 16 experts in Washington DC to discuss current issues and future directions of research in autoimmune diseases from the cell signaling perspective. The major topics considered included new findings on the follicular T cell cells in mice, their metabolic patterns and their control by the newly discovered T follicular regulatory cells. Current work on the metabolic pathways deemed important for the function of T cells was presented...
May 19, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28526333/systemic-manifestations-of-primary-sj%C3%A3-gren-s-syndrome-in-the-nod-b10sn-h2-b-j-mouse-model
#15
Jeremy Kiripolsky, Long Shen, Yichen Liang, Alisa Li, Lakshmanan Suresh, Yun Lian, Quan-Zhen Li, Daniel P Gaile, Jill M Kramer
Animal models that recapitulate human disease are crucial for the study of Sjögren's Syndrome (SS). While several SS mouse models exist, there are few primary SS (pSS) models that mimic systemic disease manifestations seen in humans. Similar to pSS patients, NOD.B10Sn-H2(b)/J (NOD.B10) mice develop exocrine gland disease and anti-nuclear autoantibodies. However, the disease kinetics and spectrum of extra-glandular disease remain poorly characterized in this model. Our objective was to characterize local and systemic SS manifestations in depth in NOD...
May 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28522286/increased-proportions-of-functionally-impaired-regulatory-t-cell-subsets-in-systemic-sclerosis
#16
Emese Ugor, Diána Simon, Giovanni Almanzar, Ramóna Pap, József Najbauer, Péter Németh, Péter Balogh, Martina Prelog, László Czirják, Tímea Berki
Treg abnormalities have been implicated in the pathogenesis of systemic sclerosis (SSc). Treg subpopulations and their cytokines, IL-10 and TGF-β in the peripheral blood of early stage SSc patients were investigated. We hypothesized that epigenetically regulated methylation of the FOXP3 promoter and enhancer regions are altered in Tregs of SSc patients, which might be involved in the T cell imbalance. CD4+CD25+Foxp3+CD127- Treg cells were significantly elevated in patients with diffuse cutaneous SSc and in patients with anti-Scl-70/RNA-Pol-III autoantibody positivity and with lung fibrosis...
May 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28506920/regulatory-b-cells-in-rheumatoid-arthritis-alterations-in-patients-receiving-anti-tnf-therapy
#17
Zsuzsanna Bankó, Judit Pozsgay, Tamás Gáti, Bernadette Rojkovich, Ilona Ujfalussy, Gabriella Sármay
Cytokines, including tumor necrosis factor alpha (TNFα) are involved in Rheumatoid arthritis (RA) pathogenesis by augmenting autoimmunity, sustaining long term inflammation in the synovium, and promoting joint damage. Anti-TNF therapy is one of the most efficient and widely used therapies for RA, although its mechanism is not clarified yet. Earlier we demonstrated that RA patients have a reduced number of IL-10 producing regulatory B cells (B10 cells) as compared to healthy individuals and they are functionally impaired...
May 12, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28502680/semaphorin-3a-is-a-key-player-in-the-pathogenesis-of-asthma
#18
Ronen Cozacov, Katlin Halasz, Tharwat Haj, Zahava Vadasz
Immune semaphorins are key players in regulating immune mediated inflammation. Semaphorin3A (sema3A) a secreted and membrane bound member of this family, is well reported for its properties in maintaining self-tolerance. Semaphorin3A was recognized to be a marker for T-regulatory cells (Tregs), and as such is a useful tool for assessing the status of these cells in preventing immune mediated diseases. This study was designed aiming to evaluate how sema3A is possibly involved in bronchial asthma. Here, we found sema3A serum levels and the expression of sema3A on Tregs significantly lower in patients with moderate to severe asthma when compared to healthy individuals...
May 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28502679/the-association-between-semaphorin-3a-levels-and-gluten-free-diet-in-patients-with-celiac-disease
#19
Aharon Kessel, Chen Lin, Zahava Vadasz, Regina Peri, Nasren Eiza, Drora Berkowitz
Celiac disease (CD) is an inflammatory disease affecting the small intestine. We aim to assess serum level and expression of semaphorin 3A (Sema3A) on T regulatory (Treg) cells in CD patients. Twenty-six newly diagnosed celiac patients, 13 celiac patients on a gluten-free diet and 16 healthy controls included in the study. Sema3A protein level in the serum of celiac patients was significantly higher compared to healthy group (7.17±1.8ng/ml vs. 5.67±1.5ng/ml, p=0.012). Sema3A expression on Treg cells was statistically lower in celiac patients compared to healthy subjects (p=0...
May 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28502678/il-10-producing-regulatory-b-cells-b10-cells-il-17-t-cells-and-autoantibodies-in-systemic-sclerosis
#20
Athanasios Mavropoulos, Christos Liaskos, Theodora Simopoulou, Dimitrios P Bogdanos, Lazaros I Sakkas
We aimed to analyze IL-10+ Breg (B10) cells, found to be reduced in systemic sclerosis (SSc), in relation to SSc-specific autoAbs and IL-17+ and IFNγ+ T cells in SSc. Peripheral blood B10 cells from 26 patients with SSc positive for anti-Topo I or anti-Cen autoAbs, and 12 healthy controls (HC) were studied by flow cytometry. IL-17+ and IFNγ+ T cells were also studied. B10 cells did not correlate with anti-Topo I or anti-Cen Ab levels but were inversely correlated with IL-17+ CD3+ cells and IFNγ+ CD3+ cells...
May 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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