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Anne Conrad, Mathilde Boccard, Florent Valour, Vincent Alcazer, Aydee-Tamara Tovar Sanchez, Christian Chidiac, Frédéric Laurent, Philippe Vanhems, Gilles Salles, Karen Brengel-Pesce, Boris Meunier, Sophie Trouillet-Assant, Florence Ader
INTRODUCTION: Immune reconstitution after haematopoietic stem cell transplantation (HSCT) is a complex and dynamic process, varying from a state of nearly complete immunosuppression to an expected full immune recovery. Specific vaccination guidelines recommend reimmunisation after HSCT but data regarding vaccine efficacy in this unique population are scarce. New immune functional assays could enable prediction of vaccine response in the setting of HSCT. METHODS AND ANALYSIS: A prospective, longitudinal single-centre cohort study of autologous and allogeneic HSCT recipients was designed in order to determine the vaccine response to five vaccine targets (pneumococcus, hepatitis B virus, Haemophilus Influenzae type b, tetanus and diphtheria) and to correlate it to immune function parameters...
February 15, 2019: BMJ Open
Yunzu Michele Wang, Jun Qin Mo, Dennis John Kuo, Victor Wong
We describe an unusual case of pre-B lymphoblastic leukaemia presenting with a unilateral maxillary sinus mass in which biopsies of the primary mass and the bone marrow demonstrated conflicting immunophenotyping results. The extramedullary mass was consistent with a precursor B-cell malignancy, while the bone marrow was initially reported as a possible mature B-cell malignancy. The treatments for the two are fundamentally different, which necessitated a delay in the initiation of his chemotherapy until a clear diagnosis was made...
February 15, 2019: BMJ Case Reports
Duncan Murray, Jack Luke McMurray, Suzy Eldershaw, Hayden Pearce, Nathaniel Davies, Julia J Scarisbrick, Paul Moss
Immunotherapy is a valuable treatment for many cancer patients, and there is considerable interest in understanding the mechanisms of immune evasion to guide appropriate management. Mycosis fungoides (MF) is a malignant disorder of skin-homing CD4+ T cells, and it exhibits a highly variable clinical course during which the tumor-specific immune response may be an important determinant. An unusual feature of MF is that tumor-infiltrating lymphocytes (TILs) must attempt to control a malignant cell from within their own lineage...
February 26, 2019: Blood Advances
Lindsay A Williams, Jun J Yang, Betsy A Hirsch, Erin L Marcotte, Logan G Spector
While substantial advances in the identification of cytogenomic subtypes of childhood acute lymphoblastic leukemia (ALL) have been made in recent decades, epidemiologic research characterizing the etiologic heterogeneity of ALL by subtype has not kept pace. The purpose of this review is to summarize the current literature concerning subtype-specific epidemiologic risk factor associations with ALL subtype defined by immunophenotype (e.g. B-cell vs T-cell) and cytogenomics (including gross chromosomal events characterized by recurring numerical and structural abnormalities, along with cryptic balanced rearrangements, and focal gene deletions)...
February 15, 2019: Cancer Epidemiology, Biomarkers & Prevention
Yaozhu Leng, Roberto Romero, Yi Xu, Jose Galaz, Rebecca Slutsky, Marcia Arenas-Hernandez, Valeria Garcia-Flores, Kenichiro Motomura, Sonia S Hassan, Andrea Reboldi, Nardhy Gomez-Lopez
PROBLEM: The immunophenotype of B cells at the maternal-fetal interface (decidua) in labor at term and preterm labor is poorly understood. METHOD OF STUDY: Decidual tissues were obtained from women with preterm or term labor and from non-labor gestational age-matched controls. Immunophenotyping of decidual B cells was performed using multi-color flow cytometry. RESULTS: 1) In the absence of acute or chronic chorioamnionitis, total B cells were more abundant in the decidua parietalis of women who delivered preterm than those who delivered at term, regardless of the presence of labor; 2) decidual transitional and naïve B cells were the most abundant B-cell subsets; 3) decidual B1 B cells were increased in women with labor at term or preterm labor and chronic chorioamnionitis compared to those without this placental lesion; 4) decidual transitional B cells were reduced in women with preterm labor compared to those without labor; 5) naïve, class-switched, and non-class-switched B cells in the decidual tissues underwent mild alterations with the process of preterm labor and/or placental inflammation; 6) decidual plasmablasts seemed to increase in women with labor at term or preterm labor with chronic chorioamnionitis; and 7) decidual B cells expressed high levels of interleukin (IL)-12, IL-6 and/or IL-35...
February 15, 2019: American Journal of Reproductive Immunology: AJRI
Hsiling Chiu, Preeti Trisal, Chad Bjorklund, Soraya Carrancio, Estela G Toraño, Carla Guarinos, Despoina Papazoglou, Patrick R Hagner, Asma Beldi-Ferchiou, Karin Tarte, Marie-Hélène Delfau-Larue, Franck Morschhauser, Alan G Ramsay, Anita K Gandhi
Chemotherapy plus rituximab has been the mainstay of treatment for follicular lymphoma (FL) for two decades but is associated with immunosuppression and relapse. In phase 2 studies, lenalidomide combined with rituximab (R2 ) has shown clinical synergy in front-line and relapsed/refractory FL. Here, we show that lenalidomide reactivated dysfunctional T and Natural Killer (NK) cells ex vivo from FL patients by enhancing proliferative capacity and T-helper cell type 1 (Th1) cytokine release. In combination with rituximab, lenalidomide improved antibody-dependent cellular cytotoxicity in sensitive and chemo-resistant FL cells, via a cereblon-dependent mechanism...
February 14, 2019: British Journal of Haematology
Małgorzata Dawidowska, Roman Jaksik, Monika Drobna, Bronisława Szarzyńska-Zawadzka, Maria Kosmalska, Łukasz Sędek, Ludomiła Machowska, Anna Lalik, Monika Lejman, Marek Ussowicz, Krzysztof Kałwak, Jerzy R Kowalczyk, Tomasz Szczepański, Michał Witt
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy originating from T-cell precursors. The genetic landscape of T-ALL has been largely characterized by next-generation sequencing. Yet, the transcriptome of miRNAs (miRNome) of T-ALL has been less extensively studied. Using small RNA sequencing, we characterized the miRNome of 34 pediatric T-ALL samples, including the expression of isomiRs and the identification of candidate novel miRNAs (not previously annotated in miRBase). For the first time, we show that immunophenotypic subtypes of T-ALL present different miRNA expression profiles...
February 11, 2019: Neoplasia: An International Journal for Oncology Research
Estelle Dubruc, Maria Teresa Alvarez Flores, Yannick Bernier, Lucia Gherasimiuc, Alexandre Ponti, Patrice Mathevet, Massimo Bongiovanni
Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are rare uterine neoplasms of uncertain etiology that resemble the sex cord tumors of the ovary and display a combined sex cord, epithelial, and smooth muscle immunophenotype. Most tumors are associated with a benign clinical course. We report the first cytological description of uterine UTROSCTs in liquid-based cervical cytology (LBC). A menopausal woman was discovered to have a uterine intraluminal polypoid mass protruding through the vagina. A Pap test was performed, and the LBC preparation showed isolated tumor cells with scant cytoplasm and slightly irregular, ovoid nuclei with fine chromatin and small nucleoli...
February 13, 2019: Diagnostic Cytopathology
Alejandra Jaque, Alexandra Mereniuk, Scott Walsh, Neil H Shear, Shachar Sade, Brandon Zagorski, Raed Alhusayen
BACKGROUND: Mycosis fungoides (MF) typically has a CD4+ CD8- T-cell phenotype. Rare cases of CD4- CD8+ , CD4- CD8- , or CD4+ CD8+ immunophenotypes have been described. Little is known about the impact of MF immunophenotypes on disease behavior. METHODS: We conducted a retrospective cohort study to review all cases of MF from 2007 to 2017 from Sunnybrook Health Sciences Centre, Toronto, Canada. CD4+ CD8- (Group 1) was compared to the three less common subtypes (Group 2) with respect to stage at diagnosis, progression, and transformation...
February 14, 2019: International Journal of Dermatology
Oksana Sokhatska, Eva Padrão, Bernardo Sousa-Pinto, Marília Beltrão, Patrícia Caetano Mota, Natália Melo, Luís Delgado, António Morais
BACKGROUND: Diffuse lung diseases (DLD) are characterized by different immunophenotypes in the bronchoalveolar lavage fluid (BALF). We aimed to evaluate the diagnostic value of BALF NK and NKT cell counts of patients with DLD and lymphocytic alveolitis. METHODS: We assessed 202 patients with DLD, who underwent BALF immunophenotyping. Samples were routinely processed by flow cytometry and lymphocyte subsets were compared between patients with sarcoidosis (n = 106), hypersensitivity pneumonitis (HP; n = 53), and other DLDs (n = 43)...
February 13, 2019: BMC Pulmonary Medicine
Eri Kumaki, Keisuke Tanaka, Kohsuke Imai, Yuki Aoki-Nogami, Akira Ishiguro, Satoshi Okada, Hirokazu Kanegane, Fumihiko Ishikawa, Tomohiro Morio
Mutation in the gene encoding tRNA nucleotidyl transferase, CCA-adding 1 (TRNT1), an enzyme essential for the synthesis of the 3'-terminal CCA sequence in tRNA molecules, results in a disorder that features sideroblastic anemia, B-cell immunodeficiency, periodic fever, and developmental delay. Mutations in TRNT1 are also linked to phenotypes including retinitis pigmentosa, cataracts, and cardiomyopathy. To date, it has remained unclear how defective TRNT1 is linked to B-cell deficiency. Here we report the case of a 12-year-old boy without sideroblastic anemia who harbors novel compound heterozygous mutations in TRNT1...
February 13, 2019: International Journal of Hematology
Deborah Stanco, Christian Caprara, Gianluca Ciardelli, Luca Mariotta, Mauro Gola, Greta Minonzio, Gianni Soldati
Adipose-derived stem cells (ASCs) are multipotent and immune-privileged mesenchymal cells, making them ideal candidates for therapeutic purposes to manage tendon disorders. Providing safe and regulated cell therapy products to patients requires adherence to good manufacturing practices. To this aim we investigated the in vitro tenogenic differentiation potential of ASCs using a chemically defined serum-free medium (SF) or a xenogenic-free human pooled platelet lysate medium (hPL) suitable for cell therapy and both supplemented with CTGF, TGFβ-3, BMP-12 and ascorbic acid (AA) soluble factors...
2019: PloS One
Sampsa Pikkarainen, Timi Martelius, Ari Ristimäki, Sanna Siitonen, Mikko R J Seppänen, Martti Färkkilä
OBJECTIVES: Common variable immunodeficiency (CVID) is associated with a spectrum of autoimmune complications. We studied the prevalence of gastrointestinal (GI) manifestations and infections in patients with CVID. METHODS: Complete clinical data of 132 Finnish patients with CVID (106 probable and 26 possible CVID) followed up between 2007 and 2016 were collected to a structured database. Data on endoscopies, histology, and laboratory studies were retrieved from patient files...
February 8, 2019: American Journal of Gastroenterology
Konrad Kokowski, Stefan Stangl, Sophie Seier, Martin Hildebrandt, Peter Vaupel, Gabriele Multhoff
BACKGROUND: Membrane heat shock protein 70 (mHsp70) is indicative of high-risk tumors and serves as a tumor-specific target for natural killer (NK) cells stimulated with Hsp70 peptide (TKD) and Interleukin(IL)-2. Radiochemotherapy (RCT), mHsp70-targeting NK cells, and programmed death(PD)-1 inhibition were combined to improve the efficacy of tumor-specific immune cells in a non-small cell lung carcinoma (NSCLC) patient. PATIENT: Following simultaneous RCT (64...
February 11, 2019: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
Kee Woong Kwon, So Jeong Kim, Hongmin Kim, Woo Sik Kim, Soon Myung Kang, Eunsol Choi, Sang-Jun Ha, Joo-Heon Yoon, Sung Jae Shin
Recently, interest in IL-15-differentiated cells has increased; however, the phenotypic definition of IL-15-differentiated bone marrow-derived cells (IL-15-DBMCs) is still under debate, particularly the generation of IFN-γ-producing innate cells such as premature NK (pre-mNK) cells, natural killer dendritic cells (NKDCs), interferon-producing killer dendritic cells (IKDCs), and type 1 innate lymphoid cells (ILC1s), all of which are IL-15-dependent. Here, we revisited the immunophenotypic characteristics of IFN-γ-producing IL-15-DBMCs and their functional role in the control of intracellular Mycobacterium tuberculosis (Mtb) infection...
2019: International Journal of Biological Sciences
Ziju Xu-Monette, Min Xiao, Qingyan Au, Raghav Padmanabhan, Bing Xu, Nicholas Hoe, Sandra Rodriguez-Perales, Raul Torres-Ruiz, Ganiraju Manyam, Carlo Visco, Yi Miao, Xiaohong Tan, Hongwei Zhang, Alexandar Tzankov, Jing Wang, Karen Dybkaer, Wayne Tam, Hua You, Govind Bhagat, Eric D Hsi, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Miguel A Piris, J Han van Krieken, Jane N Winter, Jason R Westin, Lan V Pham, L Jeffrey Medeiros, George Z Rassidakis, Yong Li, Gordon J Freeman, Ken H Young
PD-1/L1 and CTLA-4 blockade immunotherapies have been approved for twelve types of cancer and are being studied in diffuse large B-cell lymphoma (DLBCL), the most common aggressive B-cell lymphoma. However, whether both PD-1 and CTLA-4 checkpoints are active and clinically significant in DLBCL is unknown. Whether PD-1 ligands expressed by tumor cells or by the microenvironment of DLBCL are critical for immune checkpoint is unclear. We performed immunophenotypic profiling for 405 patients with de novo DLBCL using a MultiOmyx immunofluorescence platform and simultaneously quantitated expression/coexpression of 13 immune markers to identify prognostic determinants...
February 11, 2019: Cancer Immunology Research
Yasuo Nagafuchi, Hirofumi Shoda, Keishi Fujio
Systemic lupus erythematosus (SLE) is an autoimmune disorder with a wide range of clinical symptoms. Enormous progress has been made in the immunological and genetic understanding of SLE. However, the biology of disease heterogeneity in SLE has remained largely unexplored. Human immune profiling studies, helped by recent technological advances especially in single-cell and "omics" analyses, are now shedding light on the cellular and molecular basis of clinical symptoms and disease flares in individual patients...
February 10, 2019: Cells
Heidi Eilertsen, Per Christian Saether, Carola E Henriksson, Anne-Sofie Petersen, Tor-Arne Hagve
INTRODUCTION: The aim of the present study was to evaluate the diagnostic ability of blast flags generated by Sysmex instruments (XE/XN) by comparing with immunophenotyping by flow cytometry (IFCM). Additionally, the ability of manual microscopy and CellaVision DM96 (pre- and reclassification) to predict the presence of "true" blasts was investigated. METHODS: Blood samples (n = 240) with suspect pathology flags reported by the XE were collected from the daily workload and examined by the XN, by manual microscopy, by CellaVision DM96 and by IFCM (CytoDiff Panel)...
February 11, 2019: International Journal of Laboratory Hematology
Charlotte Lees, Colm Keane, Maher K Gandhi, Jay Gunawardana
Primary mediastinal B-cell lymphoma (PMBCL) is a distinct disease closely related to classical nodular sclerosing Hodgkin lymphoma. Conventional diagnostic paradigms utilising clinical, morphological and immunophenotypical features can be challenging due to overlapping features with other B-cell lymphomas. Reliable diagnostic and prognostic biomarkers that are applicable to the conventional diagnostic laboratory are largely lacking. Nuclear factor kappa B (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK-STAT) signalling pathways are characteristically dysregulated in PMBCL and implicated in several aspects of disease pathogenesis, and the latter pathway in host immune evasion...
February 10, 2019: British Journal of Haematology
Janina Burk, Heidrun Holland, Anne F Lauermann, Tobias May, Philipp Siedlaczek, Verena Charwat, Cornelia Kasper
Multipotent mesenchymal stromal cells (MSC) and MSC-derived products have emerged as promising therapeutic tools. To fully exploit their potential, further mechanistic studies are still necessary and bioprocessing needs to be optimized, which requires an abundant supply of functional MSC for basic research. To address this need, here we used a novel technology to establish a human adipose-derived MSC line with functional characteristics representative of primary MSC. Primary MSC were isolated and subjected to lentiviral transduction with a library of expansion genes...
February 10, 2019: Biotechnology and Bioengineering
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