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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
Ljubomir Vitkov, Matthias Hannig, Bernd Minnich, Martin Herrmann
Anti-citrullinated protein autoantibodies (ACPA) precede the onset of clinical and subclinical rheumatoid arthritis (RA). ACPA are frequently generated in further chronic inflammatory diseases, e.g. chronic obstructive pulmonary disease, lupus, periodontitis (PD), characterized by citrullination and mucosal as well as systemic autoimmunity against citrullinated proteins. PD is of particular interest, as it exhibits two sources of citrullination, namely peptidylarginine deiminase 4 (PAD4) of periodontal neutrophils and neutrophil extracellular traps (NETs) as well as the PAD of Porphyromonas gingivalis (PPAD)...
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
Malgorzata Justyna Podolska, Aparna Mahajan, Jasmin Knopf, Jonas Hahn, Sebastian Boeltz, Luis Munoz, Rostyslav Bilyy, Martin Herrmann
Rheumatic diseases are a group of inflammatory conditions that affect joints and connective tissues and are often accompanied by pain and restriction of motility. In many of these diseases, autoantibodies develop that react with molecules/structures commonly found hidden in neutrophils. Neutrophil extracellular trap (NET) formation and release is considered a defense mechanism against pathogens or endogenous danger signals and it has been associated with initial inflammatory responses. NETs are also endowed with an important resolution potential based on its intrinsic enzymatic activity, but in the case they are not timely removed from the crime scene they might modulate subsequent immune responses and contribute to the pathogenesis of chronic inflammatory diseases...
October 29, 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
Yi Chen, Ningjian Wang, Yingchao Chen, Qin Li, Bing Han, Chi Chen, Hualing Zhai, Yingli Lu
Non-alcoholic fatty liver disease (NAFLD) has been studied with inflammation and immune, but the link with thyroid autoimmunity is unreported. This study aimed to explore the direct association of NAFLD with thyroid autoimmune disease (AITD) among participants with normal thyroid stimulating hormone (TSH) levels. The data were obtained from a cross-sectional study (SPECT-China). A total of 7982 participants were enrolled. Participants underwent several checkups including peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), thyroid, and liver ultrasonography (US)...
July 17, 2018: Autoimmunity
Briton Lee, Edward W Holt, Robert J Wong, Justin L Sewell, Ma Somsouk, Mandana Khalili, Jacquelyn J Maher, Michele M Tana
Although autoimmune hepatitis (AIH) is more common in women and affects people of all races/ethnicities, there is currently limited information regarding the relationship between race/ethnicity and AIH, especially in the context of underserved populations. We aim to evaluate the relationship between race/ethnicity and AIH and better characterize its clinical features among different racial groups. We conducted a 15-year retrospective analysis, from January 2002 to June 2017, of patients seen at Zuckerberg San Francisco General Hospital (ZSFG)...
June 11, 2018: Autoimmunity
Yuquan Bai, Wulin Shen, Li Zhang, Zetian Yang, Lecai Xiong, Hexiao Tang, Jinping Zhao
Oestrogen receptor beta (ERβ) and epidermal growth factor receptor (EGFR) pathway can synergistically promote the proliferation, invasion, and metastasis of non-small-cell lung cancer (NSCLC) cells. ERβ has five subtypes, and the selective splicing of exon 8 in ERβ5 transcription translational phase makes its biological function different from other subtypes. The following study investigates whether ERβ5 interacts with EGFR pathway in lung cancer. Briefly, we found that the overexpression of ERβ5 and EGFR is associated with poor prognosis and decreased overall survival in NSCLC patients...
June 2018: Autoimmunity
Yogita Kattimani, Avinash M Veerappa
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system causing axonal injury, neuronal loss, and atrophy of the central nervous system leading to permanent neurological and clinical disability. Presence of mutations in M9 domain of HNRNPA1 and detection of autoantibodies against this domain in HNRNPA1 qualifies it as a strong candidate for causing MS. These two aspects indicate the presence of a facilitator in associating them. Varicella zoster virus (VZV), known to cause chicken pox infection in humans, is a significant contender in sensitizing the infected people towards MS...
June 2018: Autoimmunity
Marta Rydzewska, Aleksandra Góralczyk, Joanna Gościk, Natalia Wawrusiewicz-Kurylonek, Anna Bossowska, Adam Krętowski, Artur Bossowski
BACKGROUND: Autoimmune thyroid diseases are multifactorial diseases with a genetic susceptibility and environmental factors. A potential role of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, the interferon-induced helicase domain 1 (IFIH1) gene, the thyroid-stimulating hormone receptor (TSHR) gene polymorphisms on autoimmune thyroid diseases (AITDs) in adults has been established unequivocally, but there is still lack of research articles including group of children...
June 2018: Autoimmunity
Francesca Panimolle, Claudio Tiberti, Simona Granato, Antonella Anzuini, Carlotta Pozza, Andrea Lenzi, Antonio F Radicioni
OBJECTIVE: In literature, the importance of X-linked gene dosage as a contributing factor for autoimmune diseases is generally assumed. However, little information is available on the frequency of humoral endocrine organ-specific autoimmunity in X-chromosome aneuploidies. In our preliminary study, we investigated the endocrine organ-specific humoral autoimmunity relative to four different organ-specific autoimmune diseases in a group of adult 47,XXY KS patients and in adults 46,XY control males (type 1 diabetes, T1DM; Addison's disease, AD; Hashimoto thyroiditis, HT; autoimmune chronic atrophic gastritis, AG)...
June 2018: Autoimmunity
Hexiao Tang, Yuquan Bai, Wulin Shen, Yanhong Wei, Ming Xu, Xuefeng Zhou, Jinping Zhao
Tumour markers play an important role in the early diagnosis and guidance of prognosis of lung cancer. This study focused on the significance of combined monitoring of interleukin (IL)-6 and tumour markers in improving the specificity and sensitivity of lung cancer diagnosis and disease. The expression of IL-6, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) in serum of patients with non-small cell lung cancer (NSCLC) (n = 138) was significantly higher compared to patients with benign pulmonary lesions (BPL) (n = 60) and was associated with the clinicopathological features of NSCLC patients...
June 2018: Autoimmunity
Maria Celeste Fatone, Fabio Pavone, Gianfranco Lauletta, Sabino Russi
Autoimmune hemolytic anemia (AIHA) is an acquired condition characterized by the presence of autoantibodies recognizing erythrocyte-related antigens. Several components of the immune system are involved in disease pathogenesis. Among them, as for other autoimmune disorders, a role for specific CD8+ CD57+ regulatory cells subset could be hypothesized. We evaluated this lymphocyte subset by flow cytometry in 18 AIHA patients randomly selected in a retrospective population of 29 cases. Secondary forms were observed in 65...
June 2018: Autoimmunity
Nicola Bizzaro, Martina Fabris
BACKGROUND: The correct identification of anti-dense fine speckled-70 (DFS70) antibodies represents an important issue in the detection of anti-nuclear antibodies (ANAs) as performed by the indirect immunofluorescence (IIF) test on HEp-2 substrates. In this study, we have evaluated a new method for anti-DFS70 antibody detection employing HEp-2 cells knocked-out for the DFS70 antigen. METHODS: We studied 148 sera with a DFS70-like pattern (91 positive and 57 negative when tested for anti-DFS70 antibodies by a specific chemoluminescence [CLIA] method); 116 sera with infectious disease; 100 healthy donors (HDs), 139 samples from patients with a defined diagnosis of autoimmune rheumatic disease (ARD), and 242 consecutive unselected samples screened for ANA during the routine work-up...
June 2018: Autoimmunity
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June 2018: Autoimmunity
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