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Manjun Zhao, Ningning Duan, Yi Wang, Hongli Zhu, Hong Liu, Huaquan Wang, Limin Xing, Zonghong Shao
OBJECTIVE: To investigate the quantity and secretion function of cytokines-secreted CD5+ B lymphocytes in Autoimmune Haemolytic Anaemia (AIHA)/Evans syndrome (ES) patients. METHODS: Twenty-five untreated AIHA/ES patients, 28 remission AIHA/ES patients and 25 healthy controls (HCs) were enrolled in this study. The quantity of CD5+ B lymphocytes which produce interleukin-10 (IL-10) (CD5+ IL-10+ ) and transforming growth factor (TGF-β1) (CD5+ TGF-β1+ ) were detected by flow cytometry (FCM)...
February 20, 2019: Autoimmunity
Nomusa Christina Mzimela, Phikelelani Siphosethu Ngubane, Andile Khathi
Pre-diabetes is a long-lasting condition that precedes type 2 diabetes (T2D). T2D has been shown to suppress the immune response. However, it remains unclear if immune activation occurs before the onset of T2D during the progression of the pre-diabetic state. This study sought to characterize the changes in general immunity occurring during the progression from pre-diabetes to T2D. Male rats were fed a high-fat high-carbohydrate diet for 20 weeks (pre-diabetes induction period) and kept on the same diet being monitored for a further 12 weeks (experimental period)...
February 18, 2019: Autoimmunity
Yan Liang, Yajing Zhao, Xuejuan Bai, Li Xiao, Yourong Yang, Junxian Zhang, Lan Wang, Lei Cui, Tong Wang, Yingchang Shi, Weiguo Zhao, Xueqiong Wu
Tuberculosis (TB) is a major global public health problem. Latent TB infection (LTBI) is a major source of active TB. New vaccines to treat LTBI are urgently demanded. In this study, the gene encoding latency-associated antigen Rv3407 of Mycobacterium tuberculosis (MTB) rv3407 DNA vaccine was used to prepare and the immunogenicity and therapeutic effects were evaluated. Normal mice were immunized intramuscularly three times at two-week intervals with sterile water for injection, plasmid vector pVAX1, M. vaccae vaccine, ag85a DNA or rv3407 DNA...
January 11, 2019: Autoimmunity
Hexiao Tang, Yuquan Bai, Gaofeng Pan, Xianguo Wang, Yanhong Wei, Zetian Yang, Jinping Zhao
The signaling pathways of interleukin-6 (IL-6) and insulin-like growth factor 1 (IGF-1) play an important role in the progression of lung cancer, and this study aimed to explore whether they can synergistically promote the progression of non-small cell lung cancer (NSCLC). We found that IL-6, glycoprotein 130 (GP130), IGF-1 and IGF-1R were highly expressed in NSCLC (p = .000), and there was the correlation between GP130, IGF-1, and IGF-1R (p < .01). The overall survival of patients with the co-expression of GP130 and IGF-1R was significantly shorter (p = ...
January 3, 2019: Autoimmunity
Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Teppei Nakamura, Yuki Otani, Marina Hosotani, Yasuhiro Kon
Toll-like receptors (Tlrs) are sensors of danger signals which promote the activation of immune cells and intrinsic renal cells. Podocytes, the intrinsic cells of glomerulus, are continuously exposed to various plasma solutes and danger signals due to their unique location in the glomerulus. Herein, we show that Tlr9 is overexpressed in podocytes and the mechanisms which cause its injury and development of membranoproliferative glomerulonephritis (MPGN) in model BXSB/MpJ-Yaa (Yaa) mice. Yaa mice developed typical lesions of MPGN and showed strong expression of Tlr9 mRNA throughout the glomerulus particularly toward the periphery of the glomerulus...
December 28, 2018: Autoimmunity
Gali Aljadeff, Eleonora Longhi, Yehuda Shoenfeld
The multifactorial etiology of autoimmune diseases has been studied at large. Genetic risk factors and environmental agents play an integral role in the pathogenesis of autoimmune processes. In recent decades, Bisphenol A (BPA), an exogenous compound found in polycarbonate plastic, has gained attention for its harmful multifocal effects on a diverse subset of systemic pathways, potentially contributing to disease onset and exacerbation. BPA is a xenoestrogen used globally in the manufacture of daily use products including plastic storage containers, water and infant bottles, and food and drink packaging...
December 28, 2018: Autoimmunity
Eman H El-Sayed, Mai H Saleh, Mohsen H Al-Shahaly, Eman A Toraih, Amal Fathy
BACKGROUND: Rheumatoid arthritis (RA) is a joint destructive disorder with great morbidity. Unraveling genetic determinants causing the disease would pave the road towards early detection and precise medicine. Interleukin 37 (IL-37), a natural inhibitor of innate immunity, was shown to be a key modulator in RA. Plasma levels were deregulated and correlated with disease activity. Therefore, we hypothesized the IL-37 gene variants could influence the clinical characteristics of RA patients...
December 28, 2018: Autoimmunity
Scott J Pilla, Ashok Balasubramanyam, William C Knowler, Mariana Lazo, David M Nathan, Xavier Pi-Sunyer, Jeanne M Clark, Nisa M Maruthur
Islet autoantibodies are typically associated with type 1 diabetes, but have been found in patients diagnosed with type 2 diabetes in whom they are associated with lower adiposity. The significance of autoantibody positivity in overweight and obese patients is not well understood. The aim of this study was to determine the prevalence and clinical significance of islet autoantibodies in overweight/obese adults diagnosed with type 2 diabetes. This study includes 204 participants at one site of the multicenter Look AHEAD (Action for Health in Diabetes) trial (ClinicalTrials...
December 2018: Autoimmunity
Takayuki Kunisato, Mikio Watanabe, Naoya Inoue, Azusa Okada, Takashi Nanba, Wataru Kobayashi, Yuka Inoue, Yuka Katsumata, Naoki Omori, Takayuki Nobuhara, Kazuya Takemura, Yoh Hidaka, Yoshinori Iwatani
The prognosis of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's disease (HD) is difficult to predict. We previously suggested that Th17 cells may be associated with the pathogenesis of AITD. However, the association between gene polymorphisms in Th17-related genes and the prognosis of AITD was not clarified. To clarify this association, we genotyped 12 polymorphisms in 11 Th17-related genes (IL1Ra, IL6R, IL17R, IL21R, IL23R, CCR6, SOCS3, RORC, IL17A, IL17F and IL21) in 142 HD patients including 58 patients with severe HD and 48 patients with mild HD, 170 patients with GD including 81 patients with intractable GD and 49 patients with GD in remission, and 84 healthy volunteers...
November 24, 2018: Autoimmunity
Mara Cerqueiro Bybrant, Lena Grahnquist, Eva Örtqvist, Cecilia Andersson, Gun Forsander, Helena Elding Larsson, Åke Lernmark, Johnny Ludvigsson, Claude Marcus, Annelie Carlsson, Sten A Ivarsson
OBJECTIVES: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D). PATIENTS AND METHODS: Dried blood spots and serum samples were taken at diagnosis from children <18 years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D...
November 16, 2018: Autoimmunity
Karla Consort Ribeiro, Roberto Perez Campelo, Daniela Del Rosário Flores Rodrigues, Elisabete C Mattos, Izaira Trincani Brandão, Célio Lopes da Silva, Eliete Bouskela, Camila Guerra Martinez, Eleonora Kurtenbach
Autoantibodies against the M2 subtype of muscarinic acetylcholine receptors with functional activities have been found in the sera of patients with dilated cardiomyopathy (DCM), and the second extracellular loop has been established as the predominant epitope. However, it has been shown that the third intracellular loop is recognized by Chagas disease patients with severe cardiac dysfunction. In this work, BALB/c mice were immunized with plasmids encoding these two epitopes, and a control group received the empty plasmid (pcDNA3 vector)...
November 13, 2018: Autoimmunity
Stephen L Rego, Scott Harvey, Sean R Simpson, Wayne O Hemphill, Zachariah A McIver, Jason M Grayson, Fred W Perrino
Anaemia is commonly observed in chronic inflammatory conditions, including systemic lupus erythematosus (SLE), where ∼50% of patients display clinical signs of anaemia. Mutation at the aspartate residue 18 of the three prime repair exonuclease 1 (TREX1) gene causes a monogenic form of cutaneous lupus in humans and the genetically precise TREX1 D18N mice recapitulate a lupus-like disease. TREX1 degrades single- and double-stranded DNA (dsDNA), and the link between failed DNA degradation by nucleases, including nucleoside-diphosphate kinases (NM23H1/H2) and Deoxyribonuclease II (DNase II), and anaemia prompted our studies to investigate whether TREX1 dysfunction contributes to anaemia...
November 13, 2018: Autoimmunity
Nishant Dwivedi, Marko Radic
The causes and mechanisms of autoimmune disease pose continuing challenges to the scientific community. Recent clues implicate a peculiar feature of neutrophils, their ability to release nuclear chromatin in the form of neutrophil extracellular traps (NETs), in the induction or progression of autoimmune disease. Efforts to define the beneficial versus detrimental effects of NET release have, as yet, only partially revealed mechanisms that guide this process. Evidence suggests that the process of NET release is highly regulated, but the details of regulation remain controversial and obscure...
November 10, 2018: Autoimmunity
Murad Alahdal, Jing Liangliang, Lu Shiping, Xing Yun, Huashan Gao, Zhou Jialei, Waseem Hassan, Liang Jin, Cao Rongyue
Therapeutic efficacy of P277 against type 1 diabetes was extensively investigated and clinically evidenced. Clinical trials Phases I and II concluded promising results, while the data of P277 immunogenicity in Phase III trials represented weak responses that led to abolish medical use. But, a therapeutic performance of P277 cannot be forgotten. So, in order to exploit its therapeutic benefits and improve its immunogenicity, we developed a new analogue VP to optimize therapeutic efficacy and enhancing immunosuppressive modulations...
November 1, 2018: Autoimmunity
Daniel Appelgren, Charlotte Dahle, Jasmin Knopf, Rostyslav Bilyy, Volodymyr Vovk, Pia C Sundgren, Anders A Bengtsson, Jonas Wetterö, Luis E Muñoz, Martin Herrmann, Anders Höög, Christopher Sjöwall
Although neutrophil extracellular traps (NETs) have been highlighted in several systemic inflammatory diseases, their clinical correlates and potential pathological role remain obscure. Herein, we describe a dramatic onset of systemic lupus erythematosus (SLE) with clear-cut pathogenic implications for neutrophils and NET formation in a young woman with cardiac (Libman-Sacks endocarditis) and central nervous system (psychosis and seizures) involvement. Despite extensive search, circulating antiphospholipid autoantibodies, a hallmark of Libman-Sacks endocarditis, could not be detected...
October 28, 2018: Autoimmunity
S Paryzhak, T Dumych, I Mahorivska, M Boichuk, G Bila, S Peshkova, T Nehrych, R Bilyy
During NET formation, the content of neutrophils granules is released into the intercellular milieu. Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992)...
October 28, 2018: Autoimmunity
Chenggui Miao, Jun Chang, Jinfeng Dou, Youyi Xiong, Guoliang Zhou
In this work, the expression of secreted frizzled related protein 2 (SFRP2) in rheumatoid arthritis (RA) model rats and the mechanisms of SFRP2 on the RA pathogenesis were investigated. Data suggested that SFRP2 was significantly down-regulated in RA model rats compared with normal control, and overexpression of SFRP2 suppressed the RA pathogenesis and the canonical Wnt signaling in fibroblast-like synovial cells (FLS) from RA model rats, whereas knockdown of SFRP2 got an opposite observation. Interestingly, 5-azadC treatment up-regulated the SFRP2 expression, inhibited the FLS proliferation, suppressed the expression of IL-6 and IL-8 and the fibronectin production, suggesting that the decreased SFRP2 in RA model rats was due to the DNA methylation...
October 20, 2018: Autoimmunity
Jiwei Zhao, Yanxia Chen, Qing Zhao, Jie Shi, Wei Yang, Zhongliang Zhu, Wenge Yu, Jinju Guan, Yingxiang Song, Hui Wu, Weidong Jin, Yonglie Zhou, Jinlin Liu
OBJECTIVE: Hashimoto's thyroiditis (HT) is characterized by autoantibodies targeting the thyroid. Abnormal CD4+ CXCR5+ T cell levels were previously shown to be associated with HT. However, Tfh cells consist of heterogeneous subpopulations, and which T follicular helper (Tfh) cell subpopulation participates in the pathogenesis of HT remains poorly understood. METHODS: Thirty healthy controls (HCs) and 52 HT patients were enrolled in the study. The percentages of Tfh, ICOS+ Tfh, PD1+ Tfh, Tfh1, Tfh2, Tfh17, effector Tfh, resting Tfh, effector memory Tfh, central memory Tfh, and naïve Tfh cells in the peripheral blood were all determined via flow cytometry, and the associations between the percentages of these cells and thyroid function indices were also investigated...
October 20, 2018: Autoimmunity
Jiwei Zhao, Yanxia Chen, Zhenyao Xu, Wei Yang, Zhongliang Zhu, Yingxiang Song, Jinlin Liu
OBJECTIVE: Follicular T helper (Tfh) cells are involved in the pathogenesis of Hashimoto's thyroiditis (HT), while follicular T regulatory (Tfr) cells inhibit Tfh cells, which mediate B cell responses. However, the role of Tfr cells in HT remains unclear. METHODS: Forty-six healthy controls (HCs) and 84 HT patients were enrolled in the study. The percentage of Treg cells, CXCR5- Treg cells, and Tfr cells; the Tfr/Tfh ratio; and the percentage of ICOS, PD-1, CTLA-4, CXCR3 and CCR6 in Tfr cells were investigated; furthermore, the associations between the percentage of Tfr cells or the Tfr/Tfh ratio and the autoantibody indices were investigated...
October 20, 2018: Autoimmunity
Saeed Mohammadi, Ali Memarian, Sima Sedighi, Nasser Behnampour, Yaghoub Yazdani
Macrophages are versatile phagocytic cells in immune system with immunoregulatory functions. However, the removal of apoptotic cells by macrophages is disturbed in systemic lupus erythematosus (SLE). Aryl hydrocarbon receptor (AhR) is a ligand-activated cytoplasmic receptor and transcription factor with diverse effects on immune response. Indole-3-carbinol (I3C) is an AhR agonist which has been implicated as a beneficial factor in regulating inflammation and cytokine expression in murine models of SLE. However, the molecular mechanisms are not thoroughly studied...
October 5, 2018: Autoimmunity
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