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Barbara L Andersen, Neha Godiwala Goyal, David M Weiss, Travis D Westbrook, Kami J Maddocks, John C Byrd, Amy J Johnson
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia, with profound disease-related cellular, humoral, and innate immune suppression. The objective of this study was to study the correlations between stress and disease-specific, negative prognostic cellular, cytokine, and chemokine markers in patients with CLL. METHODS: A single-group, observational design was used. Patients with relapsed/refractory CLL (N = 96) who were entering a phase 2 trial of an experimental therapy (ibrutinib) were studied...
May 14, 2018: Cancer
Elizabeth Sarmiento, Jose Cifrian, Leticia Calahorra, Carles Bravo, Sonia Lopez, Rosalia Laporta, Piedad Ussetti, Amparo Sole, Carmen Morales, Alicia de Pablos, Maria Jaramillo, Ikram Ezzahouri, Sandra García, Joaquin Navarro, Marcos Lopez-Hoyos, Javier Carbone
BACKGROUND: Infection is still a leading cause of death during the first year after lung transplantation. We performed a multicenter study among teaching hospitals to assess monitoring of early humoral immunity as a means of identifying lung recipients at risk of serious infections. METHODS: We prospectively analyzed 82 adult lung recipients at 5 centers in Spain. Data were collected before transplantation and at 7 and 30 days after transplantation. Biomarkers included IgG, IgM, IgA, complement factors C3 and C4, titers of antibodies to pneumococcal polysaccharide antigens (IgG, IgA, IgM) and antibodies to cytomegalovirus (IgG), and serum B-cell activating factor (BAFF) levels...
April 6, 2018: Journal of Heart and Lung Transplantation
Damir Bojadzic, Jinshui Chen, Oscar Alcazar, Peter Buchwald
We report the design, synthesis, and testing of novel small-molecule compounds targeting the CD40⁻CD154 (CD40L) costimulatory interaction for immunomodulatory purposes. This protein-protein interaction (PPI) is a TNF-superfamily (TNFSF) costimulatory interaction that is an important therapeutic target since it plays crucial roles in the activation of T cell responses, and there is resurgent interest in its modulation with several biologics in development. However, this interaction, just as all other PPIs, is difficult to target by small molecules...
May 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
S Twetman, M K Keller, L Lee, T Yucel-Lindberg, A M Lynge Pedersen
It has been suggested that beneficial bacteria may stimulate wound healing. The aim was to investigate the effect of topical applications of probiotic lactobacilli on the healing of standardised oral wounds. This pilot study employed a randomised, placebo-controlled, double-blind cross-over design. Standardised biopsies were punched in the oral mucosa of 10 healthy volunteers, with and without exposure to two strains of Lactobacilli reuteri administrated as lozenges and topical oil. The healing was scored clinically after 2, 5 and 8 days...
May 4, 2018: Beneficial Microbes
Zayed Attia, John C Rowe, Eunsoo Kim, Sanjay Varikuti, Haley H Steiner, Ahmad Zaghawa, Hany Hassan, Estelle Cormet-Boyaka, Abhay R Satoskar, Prosper N Boyaka
It is well established that dendritic cells and macrophages play a role in antigen presentation to B and T cells and in shaping B and T cell responses via cytokines they produce. We have previously reported that depletion of neutrophils improves the production of mucosal IgA after sublingual immunization with Bacillus anthracis edema toxin as adjuvant. These past studies also demonstrated that an inverse correlation exists between the number of neutrophils and production of IgA by B cells. Using specific inhibitors of elastase, we addressed whether the elastase activity of neutrophil could be the factor that interferes with production of IgA and possibly other immunoglobulin isotypes...
April 30, 2018: European Journal of Immunology
Il-Young Hwang, Cedric Boularan, Kathleen Harrison, John H Kehrl
The follicular (FO) versus marginal zone (MZ) B cell fate decision in the spleen depends upon BCR, BAFF, and Notch2 signaling. Whether or how Gi signaling affects this fate decision is unknown. Here, we show that direct contact with Notch ligand expressing stromal cells (OP9-Delta-like 1) cannot promote normal MZ B cell development when progenitor B cells lack Gαi proteins, or if Gi signaling is disabled. Consistent with faulty ADAM10-dependent Notch2 processing, Gαi -deficient transitional B cells had low ADAM10 membrane expression levels and reduced Notch2 target gene expression...
2018: Frontiers in Immunology
Lyvia Fourcade, Johanne Poudrier, Michel Roger
Africa accounts for the majority of global human immunodeficiency virus (HIV) infections, most of which affect women through heterosexual intercourse. Currently, there is no cure for HIV and the development of vaccines and microbicides remains the best solution to eradicate the pandemic. We and others have identified HIV highly-exposed seronegative (HESN) individuals among African female commercial sex workers (CSWs). Analyses of genital samples from HESNs have demonstrated potent innate and anti-inflammatory conditions, HIV-specific CD4⁺ and CD8⁺ T-cells as well as immunoglobulins (Igs), and increased regulatory cell populations, all of which support a delicate balance between strength and control against HIV intrusion...
April 23, 2018: Viruses
Sankar Renu, Santosh Dhakal, Eunsoo Kim, Jonathan Goodman, Yashavanth S Lakshmanappa, Michael J Wannemuehler, Balaji Narasimhan, Prosper N Boyaka, Gourapura J Renukaradhya
Intranasal vaccination of pigs with poly lactic-co-glycolic acid and polyanhydride nanoparticles delivered inactivated influenza virus provides cross-reactive T-cell response, but not antibody response, resulting in incomplete protection and no reduction in nasal virus shedding. Expression of BAFF and Th2 transcription factor GATA-3 were downregulated in lungs of pigs vaccinated with influenza nanovaccine, but in mice it upregulated the expression of BAFF and cytokine TGFβ in cervical lymph nodes. However, the intranasal iNKT cell adjuvant, α-Galctosylceramide upregulates the expression of BAFF in pig lungs...
April 11, 2018: Cellular Immunology
Weili Shi, Qiaofang Hou, Hui Zhang, Guiyu Lou, Yuwei Zhang, Shixiu Liao
OBJECTIVE: To detect potential mutation of the WAS gene in a Chinese family affected with Wiskott-Aldrich syndrome. METHODS: Peripheral blood samples were collected from the proband and his family members. All exons and flanking regions of the WAS gene were subjected to PCR amplification - Sanger sequencing as well as restriction endonuclease analysis. Plasma level of B-cell activating factor (BAFF) was also determined for all family members. RESULTS: A hemizygous mutation (c...
April 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Julie Tellier
No abstract text is available yet for this article.
April 5, 2018: Blood
Takayuki Yamamoto, Kenta Iwasaki, Kenta Murotani, Asami Takeda, Kenta Futamura, Manabu Okada, Makoto Tsujita, Takahisa Hiramitsu, Norihiko Goto, Shunji Narumi, Yoshihiko Watarai, Kunio Morozumi, Kazuharu Uchida, Takaaki Kobayashi
Noninvasive methods for the early diagnosis of chronic antibody-mediated rejection (cAMR) are desired for patients with de novo (dn) donor-specific HLA antibody (DSA). This study aimed to elucidate the clinical relevance of immune-related gene expression in peripheral blood of kidney transplant recipients. The expression levels of fourteen key molecules (Foxp3, CTLA-4, CCR7, TGF-β, IGLL-1, IL-10, ITCH, CBLB, Bcl-6, CXCR5, granzyme B, CIITA, Baff, TOAG-1/TCAIM) related to regulatory/cytotoxic function of immune cells were compared in 93 patients, which were divided into Groups A (clinical cAMR with dn DSA, n=16), B (subclinical cAMR with dn DSA, n=17), C (negative cAMR with dn DSA, n=21) and D (stable function without dn DSA, n=39)...
March 31, 2018: Human Immunology
Katherine James, Chimwemwe Chipeta, Antony Parker, Stephen Harding, Simon J Cockell, Colin S Gillespie, Jennifer Hallinan, Francesca Barone, Simon J Bowman, Wan-Fai Ng, Benjamin A Fisher
Objectives: B-cell activating factor (BAFF), β-2 microglobulin (β2M) and serum free light chains (FLCs) are elevated in primary SS (pSS) and associated with disease activity. We aimed to investigate their association with the individual disease activity domains of the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in a large well-characterized pSS cohort. Methods: Sera from pSS patients enrolled in the UK Primary Sjögren's Syndrome Registry (UKPSSR) (n = 553) and healthy controls (n = 286) were analysed for FLC (κ and λ), BAFF and β2 M...
March 28, 2018: Rheumatology
Rosanna Coppo
IgA nephropathy, identified 50 years ago in France, is the most frequent glomerular disease worldwide. The course is variable, but in most of the cases there is a relentless decline in renal function, reaching end-stage renal failure in 10-60% of the cases after 10 years and in 40% after 20 years. These data justify the interest for finding a suitable therapeutic approach particularly in progressive cases. A supportive care, including renin-angiotensin system inhibitors is the priority in cases with slowly declining renal function, particularly when developing proteinuria...
April 2018: Néphrologie & Thérapeutique
Behzad Bidadi, Duan Liu, Krishna R Kalari, Matthias Rubner, Alexander Hein, Matthias W Beckmann, Brigitte Rack, Wolfgang Janni, Peter A Fasching, Richard M Weinshilboum, Liewei Wang
Neutropenia secondary to chemotherapy in breast cancer patients can be life-threatening and there are no biomarkers available to predict the risk of drug-induced neutropenia in those patients. We previously performed a genome-wide association study (GWAS) for neutropenia events in women with breast cancer who were treated with 5-fluorouracil, epirubicin and cyclophosphamide and recruited to the SUCCESS-A trial. A genome-wide significant single-nucleotide polymorphism (SNP) signal in the tumor necrosis factor superfamily member 13B ( TNFSF13B ) gene, encoding the cytokine B-cell activating factor (BAFF), was identified in that GWAS...
2018: Frontiers in Pharmacology
Woori Shin, Hyun Tae Lee, Heejin Lim, Sang Hyung Lee, Ji Young Son, Jee Un Lee, Ki-Young Yoo, Seong Eon Ryu, Jaejun Rhie, Ju Yeon Lee, Yong-Seok Heo
BAFF, a member of the TNF superfamily, has been recognized as a good target for autoimmune diseases. Belimumab, an anti-BAFF monoclonal antibody, was approved by the FDA for use in treating systemic lupus erythematosus. However, the molecular basis of BAFF neutralization by belimumab remains unclear. Here our crystal structure of the BAFF-belimumab Fab complex shows the precise epitope and the BAFF-neutralizing mechanism of belimumab, and demonstrates that the therapeutic activity of belimumab involves not only antagonizing the BAFF-receptor interaction, but also disrupting the formation of the more active BAFF 60-mer to favor the induction of the less active BAFF trimer through interaction with the flap region of BAFF...
March 23, 2018: Nature Communications
Michele Vigolo, Melissa G Chambers, Laure Willen, Dehlia Chevalley, Klaus Maskos, Alfred Lammens, Aubry Tardivel, Dolon Das, Christine Kowalczyk-Quintas, Sonia Schuepbach-Mallepell, Cristian R Smulski, Mahya Eslami, Antonius Rolink, Edith Hummler, Eileen Samy, Yves Fomekong Nanfack, Fabienne Mackay, Maofu Liao, Henry Hess, Xuliang Jiang, Pascal Schneider
The B cell survival factor (TNFSF13B/BAFF) is often elevated in autoimmune diseases and is targeted in the clinic for the treatment of systemic lupus erythematosus. BAFF contains a loop region designated the flap, which is dispensable for receptor binding. Here we show that the flap of BAFF has two functions. In addition to facilitating the formation of a highly active BAFF 60-mer as shown previously, it also converts binding of BAFF to TNFRSF13C (BAFFR) into a signaling event via oligomerization of individual BAFF-BAFFR complexes...
March 23, 2018: Nature Communications
Joan T Merrill, William R Shanahan, Morton Scheinberg, Kenneth C Kalunian, David Wofsy, Renee S Martin
BACKGROUND: Targeted inhibitors of B-cell activating factor (BAFF) have been evaluated in phase III trials in over 4000 patients with systemic lupus erythematosus (SLE). Post hoc analyses of these studies identify greater treatment effect in patients entering with higher disease activity, greater corticosteroid doses, anti double-stranded DNA (dsDNA) and low complement C3 or C4. OBJECTIVES: To evaluate the efficacy and safety of blisibimod, a BAFF inhibitor, in a population of patients with SLE enriched for high disease activity...
March 21, 2018: Annals of the Rheumatic Diseases
Corinna Schmitz, Heidi Noels, Omar El Bounkari, Eva Straussfeld, Remco T A Megens, Marieke Sternkopf, Setareh Alampour-Rajabi, Christine Krammer, Pathricia V Tilstam, Norbert Gerdes, Christina Bürger, Aphrodite Kapurniotu, Richard Bucala, Joachim Jankowski, Christian Weber, Jürgen Bernhagen
The inflammatory cytokine macrophage migration-inhibitory factor (MIF) promotes atherosclerosis via lesional monocyte and T-cell recruitment. B cells have emerged as important components in atherogenesis, but the interaction between MIF and B cells in atherogenesis is unknown. Here, we investigated the atherosclerotic phenotype of Mif-gene deletion in Apoe-/- mice. Apoe-/- Mif-/- mice on a Western-diet exhibited strongly reduced atherosclerotic lesions in brachiocephalic artery (BC) and abdominal aorta compared with controls...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Roberta Magliozzi, Owain W Howell, Richard Nicholas, Carolina Cruciani, Marco Castellaro, Chiara Romualdi, Stefania Rossi, Marco Pitteri, Maria Donata Benedetti, Alberto Gajofatto, Francesca B Pizzini, Stefania Montemezzi, Sarah Rasia, Ruggero Capra, Alessandra Bertoldo, Francesco Facchiano, Salvatore Monaco, Richard Reynolds, Massimiliano Calabrese
OBJECTIVE: Gray matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in multiple sclerosis (MS), but can these changes be identified in the patient early in the disease course? METHODS: To identify possible biomarkers linking meningeal inflammation, GM damage, and disease severity, gene and protein expression were analyzed in meninges and cerebrospinal fluid (CSF) from 27 postmortem secondary progressive MS and 14 control cases...
April 2018: Annals of Neurology
Latika Gupta, Smriti Chaurasia, Puja Srivastava, Sanjay Dwivedi, Able Lawrence, Ramnath Misra
We studied the serum levels of B cell survival factors BAFF and APRIL in patients with idiopathic inflammatory myositis (IIM) and their relation with clinical and autoantibodies. Seventy-five patients (51 females and 24 males) with IIM (Bohan and Peter's criteria 1975) and 25 healthy adults were analyzed for BAFF, APRIL and IL-17 by ELISA, and myositis-specific and associated antibodies (MSA and MAA) using line immunoblot assay. Of the 75 patients, 59 were adults, 42 had Dermatomyositis (DM), and 17 had Polymyositis...
May 2018: Clinical Rheumatology
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