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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
R Magliozzi, O W Howell, R Nicholas, C Cruciani, M Castellaro, C Romualdi, S Rossi, M Pitteri, M D Benedetti, A Gajofatto, F B Pizzini, S Montemezzi, S Rasia, R Capra, A Bertoldo, F Facchiano, S Monaco, R Reynolds, M Calabrese
OBJECTIVE: Grey 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 analysed in meninges and CSF from 27 post-mortem secondary progressive MS (SPMS) and 14 control cases...
March 8, 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...
March 7, 2018: Clinical Rheumatology
R Rahmanzadeh, M S Weber, W Brück, S Navardi, M A Sahraian
For decades, B cells were ignored in multiple sclerosis (MS) pathogenesis, and the disease was always regarded as a T cell-mediated disorder. Recent evidence shows that there is an antigen-driven B-cell response in the central nervous system of patients with MS, and memory B cells/plasma cells are detectable in MS lesions. The striking efficacy of B cell-depleting therapies in reducing the inflammatory activity of the disease highlights that B cells may play more pathogenetic roles than expected. B cells express several unique characteristic markers on their surface, for example, CD19, CD20 molecules, that provide selective targets for monoclonal antibodies...
March 7, 2018: Acta Neurologica Scandinavica
Lorena Alvarez, Leyre Riancho, Jime Calvo-Alén, Marcos Lopez Hoyos, Victor Martinez-Taboada
BACKGROUND: B-cell differentiation and B-cell tolerance checkpoints may be different in antiphospholipid syndrome (APS) from systemic lupus erythematosus (SLE) and can help to understand differences between them. Our aim was to define alterations of B-cell subsets in patients with primary APS (pAPS) and to compare them with SLE patients and healthy controls (HC). METHODS: Cross-sectional study including three study groups: 37 patients with pAPS, 11 SLE patients, and 21 age- and gender-matched HC...
February 16, 2018: International Journal of Molecular Sciences
K E Cervantes-Luevano, N Caronni, M C Castiello, E Fontana, G Piperno, A Naseem, P Uva, M Bosticardo, G E Marcovecchio, L D Notarangelo, M P Cicalese, A Aiuti, A Villa, F Benvenuti
BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency caused by mutations in WASp, a key regulator of cytoskeletal dynamics in hematopoietic cells. A high proportion of patients develop autoimmunity due to a breakdown in T and B cell tolerance. Moreover, excessive production of type-I interferon by plasmacytoid DCs contribute to autoimmune signs, however, the factors that triggers excessive innate activation have not been defined. OBJECTIVE: Neutrophils extracellular traps (NETs) emerged as major initiating factors in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)...
February 12, 2018: Journal of Allergy and Clinical Immunology
Hiroyoshi Doi, Eiichi Hayashi, Jun Arai, Masayuki Tojo, Kenichi Morikawa, Junichi Eguchi, Takayoshi Ito, Tatsuya Kanto, David E Kaplan, Hitoshi Yoshida
BACKGROUND AND AIM: The mechanism underlying hyperglobulinemia in cirrhosis, a long appreciated phenomenon, has never been clearly understood. The aim of this study is to investigate the basis for changes in humoral immunity observed in cirrhosis. METHODS: We retrospectively reviewed our medical record to analyze serum immunoglobulin levels in patients with liver disease. We also prospectively analyzed peripheral blood mononuclear cells (PBMC) and sera from liver disease patients...
February 10, 2018: Journal of Gastroenterology and Hepatology
Shereen Oon, Molla Huq, Timothy Godfrey, Mandana Nikpour
OBJECTIVES: To systematically review, and conduct a meta-analysis of steroid-sparing effect in, phase 3 randomized, placebo-controlled trials of biologic therapies for systemic lupus erythematosus (SLE). METHODS: Studies were identified by searching Medline (via Pubmed), EMBASE, CINAHL and SCOPUS databases, the Cochrane library, and Adult human studies published in English in the last ten years (until 18/04/2017) were included. A random-effects meta-analysis comparing a common corticosteroid-reduction endpoint in the trials of rituximab, belimumab, tabalumab and epratuzumab in SLE, was conducted...
January 6, 2018: Seminars in Arthritis and Rheumatism
Claudia Floriana Suciu, Marcella Prete, Piero Ruscitti, Elvira Favoino, Roberto Giacomelli, Federico Perosa
Atherosclerotic vasculopathy is a multifactorial process causing vessels damage and cardiovascular diseases, the leading causes of death worldwide. Atherosclerotic plaque is the asymptomatic primary, elementary, lesion of atherosclerotic vasculopathy. Accumulation of the oxidized low-density lipoprotein (oxLDL) at sub endothelial sites is now recognized as one of the major trigger events in plaque formation. The concomitant presence at the plaque site of cells belonging to either natural or adaptive immunity, the detection of autoantibodies to oxLDL, the cross-reactivity of oxLDL with anti-phospholipid antibodies, in addition to the clinical evidence of increased rates of cardiovascular events in several rheumatic diseases, has stimulated intensive research to define interconnections between the immune system and traditional risk factors at the molecular levels in order to explain accelerated atherosclerosis...
February 6, 2018: Autoimmunity Reviews
Marta Epeldegui, Larry Magpantay, Yu Guo, Gordana Halec, William G Cumberland, Priscilla K Yen, Bernard Macatangay, Joseph B Margolick, Anne F Rositch, Steven Wolinsky, Otoniel Martinez-Maza, Shehnaz K Hussain
: Chronic immune activation is a harbinger of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL), yet the underlying basis is unclear. Microbial translocation, the passage of microbial components from the gastrointestinal tract into the systemic circulation, is a source of systemic immune activation in HIV infection and may be an important contributor to the chronic B-cell activation and subsequent AIDS-NHL development. We measured biomarkers of microbial translocation including bacterial receptors/antibodies, intestinal barrier proteins, and macrophage activation-associated cytokines/chemokines, in serum from 200 HIV-infected men from the Multicenter AIDS Cohort Study prior to their AIDS-NHL diagnosis (mean = 3...
February 8, 2018: AIDS
Seung Seok Han, Seung Hee Yang, Hyung Ah Jo, Yun Jung Oh, Minkyoung Park, Joo Young Kim, Hajeong Lee, Jung Pyo Lee, Sang-Ho Lee, Kwon Wook Joo, Chun Soo Lim, Yon Su Kim, Dong Ki Kim
Background: Based on the fact that B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have a regulatory role in B cell biology, excessive levels of these cytokines can promote autoimmune pathogenesis. However, the expression and implication remain unresolved in cases of membranous nephropathy (MN). Results: The plasma BAFF levels of the primary MN patients were higher than those of healthy controls but lower than those of secondary MN patients, whereas the APRIL levels were similar between the MN patients and healthy controls...
January 9, 2018: Oncotarget
Jessica McHugh
No abstract text is available yet for this article.
February 8, 2018: Nature Reviews. Rheumatology
Gaëtane Nocturne, Xavier Mariette
Primary Sjögren syndrome (pSS) is a prototypical autoimmune disease. The involvement of B cells in the pathogenesis of pSS has long been suspected on the basis of clinical observations that include the presence of serum autoantibodies, hypergammaglobulinaemia, increased levels of free light chains and increased risk of B cell lymphoma. Moreover, the composition of the B cell subset is altered in pSS. In this Review, we discuss the mechanisms that support the increased activation of B cells in pSS, including genetic and epigenetic factors and environmental triggers that promote B cell activation via the innate immune system...
March 2018: Nature Reviews. Rheumatology
Wael Alturaiki, Amanda J McFarlane, Katie Rose, Rachel Corkhill, Paul S McNamara, Jürgen Schwarze, Brian F Flanagan
Innate immune responses are known to influence the subsequent development of adaptive immunity. We have previously shown that RSV infection of human airway epithelial cells results in production of the B cell growth factor, BAFF. To better understand how the airway responds to RSV infection by production of this and other factors to support or enhance local B cell responses to infection, we analysed the lung expression of BAFF and B cell homeostatic chemokines CXCL12, CXCL13, CCL19 and CCL21 in a murine model of RSV infection...
January 26, 2018: Cytokine
Jessica Heremans, Josselyn E Garcia-Perez, Ernest Turro, Susan M Schlenner, Ingele Casteels, Roxanne Collin, Francis de Zegher, Daniel Greene, Stephanie Humblet-Baron, Sylvie Lesage, Patrick Matthys, Christopher J Penkett, Karen Put, Kathleen Stirrups, Chantal Thys, Chris Van Geet, Erika Van Nieuwenhove, Carine Wouters, Isabelle Meyts, Kathleen Freson, Adrian Liston
BACKGROUND: Roifman syndrome is a rare inherited disorder characterized by spondyloepiphyseal dysplasia, growth retardation, cognitive delay, hypogammaglobulinemia and, in some patients, thrombocytopenia. Compound heterozygous variants in small nuclear RNA gene RNU4ATAC, necessary for U12-type intron splicing, were recently identified to drive Roifman syndrome. OBJECTIVE: We studied three patients from two unrelated kindreds harboring compound heterozygous or homozygous stem II variants in RNU4ATAC to gain insights in the mechanisms behind this disorder...
January 29, 2018: Journal of Allergy and Clinical Immunology
J Waldron, W Raymond, G Ostli-Eilertsen, J Nossent
Background Insulin growth factor-1 (IGF1) activates cell proliferation pathways and inhibits apoptosis. IGF1 is involved in tumour growth and required for T-cell independent activation of B cells. Activated B cells and autoantibody production are a hallmark of systemic lupus erythematosus (SLE). To investigate the possible role of IGF1 in SLE, we studied IGF1 across clinical characteristics, immunological biomarkers, disease activity and organ damage in SLE patients. Method In a cross-sectional study, we collected clinical characteristics, medication, disease activity (SLEDAI-2K) and organ damage (SDI) for 94 SLE patients...
January 1, 2018: Lupus
Lan-Huong Thai, Simon Le Gallou, Ailsa Robbins, Etienne Crickx, Tatiana Fadeev, Zhicheng Zhou, Nicolas Cagnard, Jérôme Mégret, Christine Bole, Jean-Claude Weill, Claude-Agnès Reynaud, Matthieu Mahévas
Previous data have suggested that B-cell-depletion therapy may induce the settlement of autoreactive long-lived plasma cells (LLPCs) in the spleen of patients with autoimmune cytopenia. To investigate this process, we used the AID-CreERT2-EYFP mouse model to follow PCs engaged in an immune response. Multiplex-PCR at the single-cell level revealed that only a small fraction of splenic PCs had a long-lived signature, whereas PCs present after anti-CD20 antibody treatment appeared more mature, similar to bone-marrow PCs...
January 29, 2018: Blood
Xiaoyu Tang, Lingling Zhang, Wei Wei
B cell activating factor (BAFF) is an important cytokine for the maintenance of B cell development, survival and homeostasis. BAFF/BAFF-R could directly activate nuclear factor kappa B (NF-κB) pathway. Tumour necrosis factor receptor-associated factors (TRAFs) are key regulatory proteins in NF-κB signaling pathways. TRAF1 enhances the activation of tumor necrosis factor receptor 2 (TNF-R2) induced by NF-κB. TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals mediated by BAFF receptor...
January 25, 2018: Immunology Letters
Lunhua Liu, Windy Rose Allman, Adam Steven Coleman, Kazuyo Takeda, Tsai-Lien Lin, Mustafa Akkoyunlu
Anti-B cell activating factor belonging to TNF-family (BAFF) antibody therapy is indicated for the treatment of patients with active systemic lupus erythematosus (SLE). We hypothesized that the BAFF receptor, transmembrane activator and calcium-modulator and cyclophilin interactor (TACI) may be responsible for the generation of antibody secreting plasma cells in SLE. To test this hypothesis, we generated TACI deficient MRL-Fas/Lpr (LPR-TACI-/-) mouse. TACI deficiency resulted in improved survival of MRL-Fas/Lpr mice and delayed production of anti-dsDNA and anti-SAM/RNP antibodies...
January 22, 2018: Scientific Reports
Abigail K Mansfield, Gabor I Keitner, Thomas Sheeran
The purpose of the present study is to compare results from the 12-item General Functioning Scale (GF-FAD) of the Family Assessment Device (FAD) to a three-item version, the Brief Assessment of Family Functioning Scale (BAFFS), designed to be used when brevity is especially important. We used principal components analysis of the GF-FAD, followed by multiple sample confirmatory factor analyses to test the robustness of the BAFFS in different samples. The BAFFS correlated highly with the GF-FAD, and demonstrated good concurrent validity with another measure of global marital functioning, the Dyadic Adjustment Scale-4 in a help-seeking sample...
January 19, 2018: Psychotherapy Research: Journal of the Society for Psychotherapy Research
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