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Autoimmune blood disorders

Pirow Bekker, Daniel Dairaghi, Lisa Seitz, Manmohan Leleti, Yu Wang, Linda Ertl, Trageen Baumgart, Sarah Shugarts, Lisa Lohr, Ton Dang, Shichang Miao, Yibin Zeng, Pingchen Fan, Penglie Zhang, Daniel Johnson, Jay Powers, Juan Jaen, Israel Charo, Thomas J Schall
The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood...
2016: PloS One
Miao Yu, Qi Long, Huan-Huan Li, Wei Liang, Yu-Hua Liao, Jing Yuan, Xiang Cheng
Myocardial injuries in viral myocarditis (VMC) are caused by viral infection and related autoimmune disorders. Recent studies suggest that IL-9 mediated both antimicrobial immune and autoimmune responses in addition to allergic diseases. However, the role of IL-9 in viral infection and VMC remains controversial and uncertain. In this study, we infected Balb/c mice with Coxsackievirus B3 (CVB3), and found that IL-9 was enriched in the blood and hearts of VMC mice on days 5 and 7 after virus infection. Most of IL-9 was secreted by CD8(+) T cells on day 5 and CD4(+) T cells on day 7 in the myocardium...
2016: Frontiers in Immunology
Nabil K El Ayoubi, Samia J Khoury
Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system. Only a few biomarkers are available in MS clinical practice, such as cerebrospinal fluid oligoclonal bands and immunoglobulin index, serum anti-aquaporin 4 antibodies, and serum anti-John Cunningham virus antibodies. Thus, there is a significant unmet need for biomarkers to assess prognosis, response to therapy, or potential treatment complications. Here we describe emerging biomarkers that are in development, focusing on those from peripheral blood...
October 18, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Anahita Alizadeh, Omid Mehrpour, Karim Nikkhah, Golnaz Bayat, Mahsa Espandani, Alireza Golzari, Lida Jarahi, Mohsen Foroughipour
INTRODUCTION: Multiple Sclerosis (MS) is defined as one of the inflammatory autoimmune disorders and is common. Its exact etiology is unclear. There are some evidences on the role of environmental factors in susceptible genetics. The aim of this study is to evaluate the possible role of Selenium, Zinc, Copper, Lead and Magnesium metals in Multiple Sclerosis patients. METHODS: In the present analytical cross-sectional study, 56 individuals including 26 patients and 30 healthy controls were enrolled in the evaluation...
August 2016: Electronic Physician
Elaine Cristina Lima Dos Santos, Amanda Chaves Pinto, Evandro Mendes Klumb, Jacyara Maria Brito Macedo
OBJECTIVE: To investigate potential associations of four substitutions in NAT2 gene and of acetylator phenotype of NAT2 with systemic lupus erythematosus (SLE) and clinical phenotypes. METHODS: Molecular analysis of 481C>T, 590G>A, 857G>A, and 191G>A substitutions in the NAT2 gene was performed by PCR-RFLP technique, using DNA extracted from peripheral blood samples obtained from patients with SLE (n=91) and controls (n=97). RESULTS AND CONCLUSIONS: The 857GA genotype was more prevalent among nonwhite SLE patients (OR=4...
September 28, 2016: Revista Brasileira de Reumatologia
Tomohiro Watanabe, Kouhei Yamashita, Masatoshi Kudo
An increased number of clinicopathological studies on autoimmune pancreatitis, cholangitis, and sialoadenitis have led to the recognition of immunoglobulin G4-related disease (IgG4-RD) as a novel disorder, characterized by elevated levels of serum IgG4 and infiltration of IgG4-expressing plasma cells in the affected organs. Although the immunological background associated with the development of IgG4-RD remains poorly understood, recent studies have suggested involvement of the innate immune response in its pathogenesis...
October 16, 2016: Current Topics in Microbiology and Immunology
John A Todd, Marina Evangelou, Antony J Cutler, Marcin L Pekalski, Neil M Walker, Helen E Stevens, Linsey Porter, Deborah J Smyth, Daniel B Rainbow, Ricardo C Ferreira, Laura Esposito, Kara M D Hunter, Kevin Loudon, Kathryn Irons, Jennie H Yang, Charles J M Bell, Helen Schuilenburg, James Heywood, Ben Challis, Sankalpa Neupane, Pamela Clarke, Gillian Coleman, Sarah Dawson, Donna Goymer, Katerina Anselmiova, Jane Kennet, Judy Brown, Sarah L Caddy, Jia Lu, Jane Greatorex, Ian Goodfellow, Chris Wallace, Tim I Tree, Mark Evans, Adrian P Mander, Simon Bond, Linda S Wicker, Frank Waldron-Lynch
BACKGROUND: Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs...
October 2016: PLoS Medicine
Petr Husa
Extrahepatic manifestations of hepatitis C virus infection (HCV) are very common. The most common of these is mixed cryoglobulinaemia. Anti-HCV antibodies and viral ribonucleic acid, HCV RNA, can be found in the cryoprecipitates, together with the rheumatoid factor. Cryoglobulins consist of a complex of immunoglobulins that in vitro precipitate upon the cooling bellow the human body temperature. Vasculitis is caused by the deposition of such immune complexes in the small blood vessels. A link with the HCV infection is considered to be established with membranoproliferative glomerulonephritis, leukocytoclastic vasculitis, lymphoproliferative disorders (in particular B cell lymphoma), Sjögren and sicca syndrome, lichen planus, porfyria cutanea tarda and diabetes mellitus...
2016: Vnitr̆ní Lékar̆ství
Xiangyu Yao, Jian Wu, Meng Lin, Wenxiang Sun, Xiao He, Channe Gowda, Silvia Bolland, Carole A Long, Rongfu Wang, Xin-Zhuan Su
Both type I interferon (IFN-I) and CD40 play a significant role in various infectious diseases, including malaria and autoimmune disorders. CD40 is mostly known to function in adaptive immunity, but previous observations of elevated CD40 levels early after malaria infection of mice led us to investigate its roles in innate IFN-I responses and disease control. Using a Plasmodium yoelii nigeriensis N67 and C57BL/6 mouse model, we showed that infected CD40-/- mice had reduced STING and serum IFN-β levels day-2 post infection, higher day-4 parasitemia, and earlier deaths...
October 2016: PLoS Pathogens
Yunfu Lv, Wan Yee Lau, Yejuan Li, Jie Deng, Xiaoyu Han, Xiaoguang Gong, Ning Liu, Hongfei Wu
Hypersplenism is a common disorder characterized by an enlarged spleen which causes rapid and premature destruction of blood cells. This review summarizes the history of hypersplenism, discuss its classification and pathogenesis, and examines its diagnosis and treatment options. We performed a comprehensive literature search using PubMed, Web of Knowledge and the China National Knowledge Infrastructure (CNKI) database, reviewed hypersplenism-related articles and summarized the major findings. According to its etiological causes, hypersplenism is characterized by splenomegaly and peripheral cytopenias...
October 2016: Experimental and Therapeutic Medicine
Wei Li, Marvin Nieman, Anirban Sen Gupta
Arterial thrombosis (blood clot) is a common complication of many systemic diseases associated with chronic inflammation, including atherosclerosis, diabetes, obesity, cancer and chronic autoimmune rheumatologic disorders. Thrombi are the cause of most heart attacks, strokes and extremity loss, making thrombosis an extremely important public health problem. Since these thrombi stem from inappropriate platelet activation and subsequent coagulation, targeting these systems therapeutically has important clinical significance for developing safer treatments...
2016: Journal of Visualized Experiments: JoVE
Yunier Rodríguez-Álvarez, Yanelys Morera-Díaz, Haydee Gerónimo-Pérez, Jorge Castro-Velazco, Rafael Martínez-Castillo, Pedro Puente-Pérez, Vladimir Besada-Pérez, Eugenio Hardy-Rando, Araceli Chico-Capote, Klaudia Martínez-Cordovez, Alicia Santos-Savio
BACKGROUND: Interleukin-15 is an immunostimulatory cytokine overexpressed in several autoimmune and inflammatory diseases such as Rheumatoid Arthritis, psoriasis and ulcerative colitis; thus, inhibition of IL-15-induced signaling could be clinically beneficial in these disorders. Our approach to neutralize IL-15 consisted in active immunization with structurally modified human IL-15 (mhIL-15) with the aim to induce neutralizing antibodies against native IL-15. In the present study, we characterized the antibody response in Macaca fascicularis, non-human primates that were immunized with a vaccine candidate containing mhIL-15 in Aluminum hydroxide (Alum), Montanide and Incomplete Freund's Adjuvant...
September 26, 2016: BMC Immunology
Gi Su Lee, Joon Cheol Park, Jeong Ho Rhee, Jong In Kim
OBJECTIVE: The goal of this study was to evaluate the etiologies and clinical outcomes of Korean recurrent pregnancy loss (RPL) patients. And also, we investigated the differences between primary and secondary RPL patients, between two and three or more pregnancy losses. METHODS: One hundred seventy eight women diagnosed as RPL were enrolled. We performed chromosomal analysis, thyroid stimulating hormone, prolactin, blood glucose, plasminogen activator inhibitor-1, natural killer cell proportion, anticardiolipin antibodies, antiphospholipid antibodies, lupus anticoagulant, anti-β2glycoprotein-1 antibodies, antinuclear antibody, protein C, protein S, antithrombin III, homocysteine, MTFHR gene, factor V Leiden mutation, and hysterosalphingography/hysteroscopic evaluation...
September 2016: Obstetrics & Gynecology Science
Etvi Juntunen, Teppo Salminen, Sheikh M Talha, Iida Martiskainen, Tero Soukka, Kim Pettersson, Matti Waris
Myxovirus resistance protein A (MxA) is a biomarker of interferon-induced gene expression state involved in many viral infections and some autoimmune disorders. It has a variety of potential utilities in clinical diagnostics, including distinguishing between bacterial and viral infections. Currently, MxA-assays are used for monitoring of IFN-β therapy in multiple sclerosis (MS) patients. As a proof-of-concept for rapid quantitative measurement of interferon response, a lateral flow immunoassay (LFIA) with upconverting nanoparticle (UCNP) reporters was developed and evaluated with clinical whole blood samples to assess the potential for a rapid and user-friendly quantitative assay for MxA, since the currently available rapid test for MxA (FebriDX) produces only qualitative result...
September 16, 2016: Journal of Medical Virology
Emil Martinka, Mariana Rončáková, Michaela Mišániková, Arash Davani
BACKGROUND: It is not always easy to classify diabetes (DM) diagnosed in adults, with a significant group of patients initially classified and treated for type 2 diabetes mellitus (DM2T) presenting signs indicating the presence of autoimmune insulitis (AI), which is characteristic of type 1 diabetes mellitus (DM1T), or latent autoimmune diabetes mellitus in adults (LADA). GOAL: Identify the proportion of patients entered with DM2T who present AI signs, and the number of patients of that proportion, who at the same time present low insulin secretion, and what clinical and laboratory manifestations could be used to differentiate between these patients...
2016: Vnitr̆ní Lékar̆ství
Rasoul Nasiri Kalmarzi, Nima Fattahi, Zeinab Kaviani, Pedram Ataee, Majid Mansouri, Ghobad Moradi, Alireza Yousefzade, Javid Morad Abbassi
BACKGROUND: T-cell response outcome is determined by co-stimulatory/inhibitory signals. Programmed cell death-1 ligand-1 (PD-L1) is a member of these co-signaling molecules with known soluble form in human serum. Soluble PD-L1 (sPD-L1) is also recognized in patients with some types of malignancy or autoimmune disorders, though there are few studies on sPD-L1 roles in allergic diseases. The purpose of this survey was to evaluate the association between sPD-L1 levels with eosinophil count as well as disease severity in allergic rhinitis (AR) patients...
September 8, 2016: Allergology International: Official Journal of the Japanese Society of Allergology
Rasoul Baharlou, Abbas Ahmadi-Vasmehjani, Mohammad Hasan Davami, Fatemeh Faraji, Mohammd Reza Atashzar, Firoozeh Karimipour, Alireza Sadeghi, Mohammad-Ali Asadi, Mahshid Khoubyari
BACKGROUND: Type 1 diabetes (T1D) is thought to involve chronic inflammation, which is manifested by the activation and expression of different inflammatory mediators. Th1- and Th17-associated cytokines are factors that have been shown to exert profound pro-inflammatory activities and have been implicated in the pathogenesis of T1D in mice and humans. OBJECTIVES: Therefore, the aim of this case control study was to determine the serum level of IL-17, IL-21, IL-27, transforming growth factor beta (TGF-β), and IFN-γ and their reciprocal relationship in Iranian T1D patients...
October 2016: Immunological Investigations
Ebru Karagün, Can Ergin, Sevim Baysak, Gönül Erden, Habibullah Aktaş, Özlem Ekiz
INTRODUCTION: Vitiligo is a common acquired pigmentary skin disorder. Vitamin D is responsible for skin pigmentation, increases tyrosinase activity and melanogenesis, and exhibits immunoregulatory functions. Low levels of vitamin D are associated with many autoimmune diseases, including systemic lupus, diabetes mellitus, rheumatoid arthritis, multiple sclerosis and alopecia areata. Few reports have evaluated serum vitamin D levels in vitiligo patients, and their results are conflicting...
August 2016: Postȩpy Dermatologii i Alergologii
Chen Chen, Sun Xiaobo, Wang Yuge, Shu Yaqing, Fang Ling, Peng Lisheng, Lu Zhengqi, Qiu Wei
OBJECTIVE: To investigate the relationship between neuromyelitis optica spectrum disorder (NMOSD) and autoantibodies. METHODS: Blood samples of 108 NMOSD patients and 38 controls were collected from January 2012 to August 2014. Immunological parameters, including anti-aquaporin 4, antinuclear, anti-ribonucleoprotein, anti-SM, anti-SSA/Ro, anti-SSB/La and anti-ribosomal P-protein autoantibodies were examined. RESULTS: The NMOSD group exhibited a significantly higher percentage of anti-aquaporin 4 antibodies compared with the control group (76...
September 8, 2016: Neuroimmunomodulation
Lukasz S Wylezinski, Jacek Hawiger
The pleiotropic cytokine interleukin 2 (IL2), disrupts the blood-brain barrier and alters brain microcirculation, underlying Vascular Leak Syndrome that complicates cancer immunotherapy with IL2. The microvascular effects of IL2 also play a role in the development of multiple sclerosis and other chronic neurological disorders. The mechanism of IL2-induced disruption of brain microcirculation has not been previously determined. We found that both human and murine brain microvascular endothelial cells express constituents of the IL2 receptor complex...
September 6, 2016: Journal of Biological Chemistry
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