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Honggeng Guan, Yuqiu Wan, Jing Lan, Qin Wang, Zhangyu Wang, Yecheng Li, Jiqing Zheng, Xueguang Zhang, Zemin Wang, Yueping Shen, Fang Xie
Regulatory T cells (Tregs), a key mediator in regulating anti-tumor immune suppression, tumor immune escape, metastasis and relapse, are considered an important therapeutic target in immunotherapy of human cancers. In the present investigation, elevated CD19(+) CD24(+) CD38(+) regulatory B cells (Bregs) were observed in PBMCs of invasive carcinoma of breast (IBCa) patients compared with that in patients with fibroadenoma (FIBma) or healthy individuals, and the positive correlation existed between Bregs and CD4(+) CD25(+) CD127(-) Tregs (r = 0...
October 20, 2016: Scientific Reports
Alberto L Horenstein, Valeria Quarona, Denise Toscani, Federica Costa, Antonella Chillemi, Vito Pistoia, Nicola Giuliani, Fabio Malavasi
Human myeloma cells express CD38 at high levels and grow in hypoxic niches inside the bone marrow. Myeloma cells respond to hypoxia with metabolic changes leading to aerobic glycolysis, thus reducing ATP and increasing NAD(+). Our hypothesis is that these conditions favor the enzymatic pathways involved in the production of adenosine in the niche. Within the niche, NAD(+) is able to activate a discontinuous adenosinergic pathway that relies upon CD38, CD203a, and CD73 or TRACP, according to the environmental pH...
October 13, 2016: Molecular Medicine
Zoltán Mátrai, Hajnalka Andrikovics, Anikó Szilvási, András Bors, András Kozma, Emma Ádám, Gabriella Halm, Éva Karászi, Attila Tordai, Tamás Masszi
The marked clinical heterogeneity of CLL makes early prognosis assessment important. Lipoprotein lipase (LPL) has been shown to confer adverse prognosis in CLL, recent data indicating it might also contribute to CLL cell survival and metabolism. We determined LPL mRNA expression in unselected peripheral blood of 84 CLL patients by RT PCR. Results were correlated with other prognostic markers and outcome. 30/84 (40 %) of cases were LPL positive based on the cutoff established by ROC analysis. In LPL positive patients significantly shorter median survival (136 vs 258 months, p < 0...
October 18, 2016: Pathology Oncology Research: POR
Muhammad Husnain, Sandra Kurtin, Nikki Barkett, Irbaz Bin Riaz, Amit Agarwal
Patients with relapsed and refractory multiple myeloma have poor prognosis. A recent analysis of patients with relapsed and refractory multiple myeloma who were refractory to both proteasome inhibitors and immunomodulatory drugs showed the median overall survival of 9 months only. Daratumumab is the first-in-class human monoclonal antibody against CD38 cells which was studied in phase I/II trials for treatment of these patients with relapsed refractory multiple myeloma. It showed an overall response rate of 36% and a median overall survival (OS) of 17 months in these patients...
2016: Case Reports in Oncological Medicine
Aviva S Mattingly, Aylin B Unsal, Julia B Purdy, Ahmed M Gharib, Adam Rupert, Joseph A Kovacs, Dorothea McAreavey, Rohan Hazra, Khaled Z Abd-Elmoniem, Colleen Hadigan
We evaluated immune activation and coronary artery plaque in young adults with HIV acquired in early life (n=31). Coronary plaque was positively associated with lipids, immune activation marker %CD8+CD38+DR, and E-selectin, a marker of endothelial inflammation. Immune activation and endothelial inflammation may drive coronary plaque formation during the early stages of atherosclerosis in the context of chronic HIV.
October 3, 2016: Pediatric Infectious Disease Journal
Mathieu F Chevalier, Céline Didier, Pierre-Marie Girard, Maria E Manea, Pauline Campa, Françoise Barré-Sinoussi, Daniel Scott-Algara, Laurence Weiss
Early events during primary HIV infection (PHI) are thought to influence disease outcome. Although a growing body of evidence suggests a beneficial role of HIV-specific CD4 help in HIV infection, it is unclear how early viral replication, systemic immune activation, and antiretroviral therapy (ART) may shape CD4 T-cell responses during PHI, and whether HIV-specific CD4 responses contribute to the high immune activation observed in PHI. Twenty-seven patients with early PHI were included in a prospective longitudinal study and 12 of them received ART after enrollment...
2016: Frontiers in Immunology
Carlos I Amaya-Chanaga, Laura Z Rassenti
Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable clinical course. The Rai and Binet staging systems are often used to predict survival. However, they do not take into account other biological characteristics of CLL cells that may influence the disease course and response to treatment. Prognostic factors such as chromosome abnormalities (trisomy 12, 11q deletions and 17p deletions), β2 microglobulin, thymidine kinase, CD38 and ZAP-70 expression, IGHV mutation status, and mutations in genes such as NOTCH1, MYD88, SF3B1, and ATM are also predictors of prognosis...
March 2016: Best Practice & Research. Clinical Haematology
Luciana De Luca, Giovanni D'Arena, Vittorio Simeon, Stefania Trino, Ilaria Laurenzana, Antonella Caivano, Francesco La Rocca, Oreste Villani, Giovanna Mansueto, Silvia Deaglio, Idanna Innocenti, Luca Laurenti, Stefano Molica, Giuseppe Pietrantuono, Angelo De Stradis, Luigi Del Vecchio, Pellegrino Musto
Microvescicles (MV) are shedding particles released by normal and neoplastic cells, whose levels in biological fluids highlight their potential role as disease biomarkers and therapeutic targets. By analyzing 131 newly diagnosed chronic lymphocytic leukemia (CLL), we found that the absolute number of serum CLL MV was significantly higher than in controls, in particular in advanced stages of disease. In addition, CD19 + and CD37+, B-cell derived MV, significantly correlated with high tumor burden. Absolute MV number cutoff selected by ROC analysis distinguished Rai stage 0 patients with shorter time to treatment (TTT) from those with more stable disease...
October 14, 2016: Leukemia & Lymphoma
Wenwen Wang, Elena Foerner, Eike Buss, Anna Jauch, Volker Eckstein, Patrick Wuchter, Anthony D Ho, Christoph Lutz
In B-cell acute lymphoblastic leukemia (B-ALL) separation of normal hematopoietic stem cells (HSC) has so far been limited to a subgroup of patients. As aldehyde dehydrogenase (ALDH)-activity is enriched in various stem cells we investigated its value for HSC isolation in adult B-ALL. Based on ALDH-activity patients could be stratified in ALDH-numerous (≥1.9% ALDH(+ )cells) and ALDH-rare (<1.9% ALDH(+ )cells) cases. In ALDH-rare B-ALL clonal-marker negative HSC could be separated by the CD34(+)CD38(-)ALDH(+ ) phenotype, whereas this separation was not possible in ALDH-numerous B-ALL...
October 13, 2016: Leukemia & Lymphoma
Christina Kalpadakis, Gerassimos A Pangalis, Theodoros P Vassilakopoulos, Maria Roumelioti, Sotirios Sachanas, Penelope Korkolopoulou, Efstathios Koulieris, Maria Moschogiannis, Xanthi Yiakoumis, Pantelis Tsirkinidis, Charalampos Pontikoglou, Dimitra Rondoyianni, Helen A Papadaki, Panayiotidis Panayiotidis, Maria K Angelopoulou
Clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ) is a recently described entity characterized by the presence of clonal B cells in the blood and/or bone marrow (BM) with morphologic and immunophenotypic features consistent with marginal zone derivation in otherwise healthy individuals. CBL-MZ is commonly associated with paraproteinemia, usually immunoglobulin M (IgM), raising diagnostic difficulties from Waldenstrom macroglobulinemia (WM). The aim of the present study was to determine the presence of MYD-88 L265P mutation in a well-characterized series of CBL-MZ to identify cases that may in fact represent WM...
October 13, 2016: Hematological Oncology
Mirjam A Lips, Jan Bert van Klinken, Hanno Pijl, Ignace Janssen, Ko Willems van Dijk, Frits Koning, Vanessa van Harmelen
INTRODUCTION: Weight loss interventions such as Roux-en-Y gastric bypass (RYGB) and very low calorie diets (VLCD) lead to improvement of glucose metabolism in obese individuals with type-2 diabetes. Weight loss can also positively influence the unfavorable inflammatory profile associated with obesity. However, a direct comparison of the effect of VLCD and RYGB on systemic inflammation is lacking. METHODS: Systemic inflammation was investigated in age- and BMI-matched morbidly obese T2DM women by determining the number and activation- or memory status of peripheral blood leukocytes by flow cytometry, in addition to measuring circulating levels of cytokines and CRP...
November 2016: Metabolism: Clinical and Experimental
Parameswaran Hari, Renju V Raj, Horatiu Olteanu
No abstract text is available yet for this article.
October 13, 2016: New England Journal of Medicine
Agata A Filip, Anna Grenda, Sylwia Popek, Dorota Koczkodaj, Małgorzata Michalak-Wojnowska, Michał Budzyński, Ewa Wąsik-Szczepanek, Szymon Zmorzyński, Agnieszka Karczmarczyk, Krzysztof Giannopoulos
Expression of microRNAs is altered in cancer. Circulating miRNA level assessed in body fluids commonly reflects their expression in tumor cells. In leukemias, however, both leukemic and nonleukemic cells compose circulating miRNA expression profile of peripheral blood. The latter contribution to extracellular miRNA pool may result in specific microenvironmental signaling, which promotes proliferation and survival. In our study, we used qT-PCR to assay peripheral blood serum of 22 chronic lymphocytic leukemia (CLL) patients for the expression of 84 miRNAs associated with activation and differentiation of B and T lymphocytes...
October 12, 2016: Annals of Hematology
Sebastian Schnitzler, Jürgen Kopitz, Konstanze Plaschke
OBJECTIVE: The role of inflammation in cognitive alterations in a post-operative setting is still not fully understood. Surgical interventions can cause systemic inflammations which eventually can induce neuroinflammation. However, the main causes of functional changes after surgery are still elusive. In this study, we investigated the role of CD38, a TNFα-inducible NADH(+) cyclase and hydrolase. We assume that CD38 overexpression impairs mitochondrial ATP synthesis. Within the hippocampus, the resulting cellular death could lead to cognitive impairment...
October 11, 2016: Neurological Research
Samaneh Kouzegaran, Soheila Siroosbakht, Bahram Fariborz Farsad, Bijan Rezakhaniha, Banafshe Dormanesh, Vahid Behnod, Amir Saber Tanha
BACKGROUND: In this study, we investigated the role and expression of interleukin (IL)-17A and IL-22 in chronic lymphocytic leukemia Methods: We evaluated the expression of markers above on CLL by ELISA, qRT-PCR, flow cytometric analysis and nonparametric Kruskal-Wallis test. RESULTS: Quantitative RT-PCR revealed that the mRNA levels of IL-17A and IL-22 in PBMCs of CLL patients were upregulated compared with those from healthy subjects (mean ± SD: 1.96 ± 0...
October 8, 2016: Cytometry. Part B, Clinical Cytometry
Geothy Chakupurakal, María Alejandra Garcia-Marquez, Alexander Shimabukuro-Vornhagen, Sandra Kluth, Hans Schlosser, Sebastian Theurich, Christof Scheid, Michael Hallek, Udo Holtick, Michael von Bergwelt-Baildon
OBJECTIVE: The role of B-cells and the subgroup of IL-10 producing B-cells, known to have a regulatory function, in patients following a haematopoetic stem cell transplant (alloSCT) has not been clearly understood to date. METHODS: We prospectively recruited 95 patients following an alloSCT and studied the B-cell reconstitution on days 30, 90 and 150. Regulatory B10-cells could be analysed in 22 consecutively recruited patients on day 30 post transplant. RESULTS: The total B-cell percentages in transplant recipients (median 0...
September 26, 2016: European Journal of Haematology
M Kabuto, N Fujimoto, T Takahashi, T Tanaka
BACKGROUND: hile the frequency of IL-10-producing B cells (B10 cells) is reported to have an inverse correlation with disease activity in some human autoimmune diseases, the association between B10 cells and autoimmune blistering diseases (AIBD) has not been well-evaluated. Although several phenotypes of human regulatory B cells have been proposed, the most appropriate one was not established. OBJECTIVE: This study aimed to evaluate B10 cells in AIBD including their phenotypes...
October 7, 2016: British Journal of Dermatology
Anmol Chandele, Jaturong Sewatanon, Sivaram Gunisetty, Mohit Singla, Nattawat Onlamoon, Rama S Akondy, Haydn Thomas Kissick, Kaustuv Nayak, Elluri Seetharami Reddy, Haroon Kalam, Dhiraj Kumar, Anil Verma, HareKrushna Panda, Siyu Wang, Nasikarn Angkasekwinai, Kovit Pattanapanyasat, Kulkanya Chokephaibulkit, Guruprasad R Medigeshi, Rakesh Lodha, Sushil Kabra, Rafi Ahmed, Kaja Murali-Krishna
: Epidemiological studies suggest that India has the largest number of dengue virus infected cases world-wide. However, there is minimal information about the immunological responses in these patients. CD8 T cells are important in dengue because they have been implicated in both protection and immunopathology. Here we provide a detailed analysis of HLA-DR(+)CD38(+) and HLA-DR(-)CD38(+) effector CD8 T- cell subsets in dengue-patients from India and Thailand. Both CD8 T cell subsets expanded and expressed markers indicative of antigen-driven proliferation; tissue-homing and cytotoxic effector functions with the HLA-DR(+)CD38(+) subset being the most striking in these effector qualities...
October 5, 2016: Journal of Virology
Lauren M K Mason, Alex Wagemakers, Cornelis van 't Veer, Anneke Oei, Wouter J van der Pot, Kalam Ahmed, Tom van der Poll, Teunis B H Geijtenbeek, Joppe W R Hovius
Borrelia burgdorferi is transmitted into the skin of the host where it encounters and interacts with two dendritic cell (DC) subsets; Langerhans cells (LCs) and dermal DCs (DDCs). These cells recognize pathogens via pattern recognition receptors, mature and migrate out of the skin into draining lymph nodes, where they orchestrate adaptive immune responses. In order to investigate the response of skin DCs during the early immunopathogenesis of Lyme borreliosis, we injected B. burgdorferi intradermally into full-thickness human skin and studied the migration of DCs out of the skin, the activation profile and phenotype of migrated cells...
2016: PloS One
Ming Hong, Yi Xia, Yu Zhu, Hui-Hui Zhao, Han Zhu, Yue Xie, Lei Fan, Li Wang, Kou-Rong Miao, Hui Yu, Yu-Qing Miao, Wei Wu, Hua-Yuan Zhu, Yao-Yu Chen, Wei Xu, Si-Xuan Qian, Jian-Yong Li
OBJECTIVES: Circulating chronic lymphocytic leukemia (CLL) cells appear not to be overly utilizing aerobic glycolysis. However, recurrent contact with CLL cells in a stromal microenvironment leads to increased aerobic glycolysis and the cells' overall glycolytic capacity, which promotes cell survival and proliferation. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been directly implicated in cellular metabolism in the control of glycolysis. TIGAR inhibits glycolysis and protects cells from intracellular reactive oxygen species (ROS)-associated apoptosis...
September 15, 2016: Leukemia Research
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