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Kerstin Sarter, Manuel Kulagin, Georg Schett, Nicola L Harris, Mario M Zaiss
Infections with different helminth species have been observed to ameliorate a variety of chronic inflammatory diseases. Herein, we show that the natural murine helminth species, Heligmosomoides polygyrus bakeri (Hp) is capable of attenuating disease severity in two different inflammatory arthritis models. Furthermore, we show that excretory-secretory (ES) products from Hp directly suppress osteoclast differentiation in vitro. Taken together, these results demonstrate that helminth infections can dampen autoimmune diseases and highlight a previously unrecognized and important role for ES products, by directly impacting on bone destruction...
January 13, 2017: Autoimmunity
Naoya Inoue, Yuka Katsumata, Mikio Watanabe, Naoko Ishido, Yu Manabe, Ayano Watanabe, Ryota Masutani, Yoh Hidaka, Yoshinori Iwatani
Graves' disease (GD) and Hashimoto's disease (HD) are autoimmune thyroid diseases (AITDs). Prognosis of AITDs varies in each patient. Toll-like receptors (TLRs) are pattern-recognition receptors that activate signaling pathways involved in the production of proinflammatory cytokines. UNC93B1 is a transcription factor of TLR7 and TLR9. In this study, we examined the association of TLR expression and TLR and UNC93B1 polymorphisms with the development and prognosis of AITDs. The ratio of intracellular TLR7 (iTLR7) and iTLR9 intensities in B cells was lower in patients with GD in remission than in patients with intractable GD (p = 0...
December 26, 2016: Autoimmunity
Moncef Zouali
Initial studies of periodontal disease suggested that T cell-mediated immunity against oral Gram-negative microorganisms is a key player in the pathogenesis of this inflammatory disease. Recent investigations, however, revealed that B cells are also engaged. Given their chief role in innate-like and adaptive immune responses, B cells could exert protective functions in periodontitis. However, the periodontal bacteria-specific antibody response is generally unable to halt disease progression in affected subjects, suggesting that the antibodies produced could exhibit low anti-bacterial blocking functions or opsonophagocytic potential, and/or unfavorable effects...
December 26, 2016: Autoimmunity
Osamu Ichii, Masataka Chihara, Shin-Hyo Lee, Teppei Nakamura, Saori Otsuka-Kanazawa, Taro Horino, Yaser Hosny Ali Elewa, Yasuhiro Kon
Inbred MRL/MpJ mice show several unique phenotypes in tissue regeneration processes and the urogenital and immune systems. Clarifying the genetic and molecular bases of these phenotypes requires the analysis of their genetic susceptibility locus. Herein, hydronephrosis development was incidentally observed in MRL/MpJ-derived chromosome 11 (D11Mit21-212)-carrying C57BL/6N-based congenic mice, which developed bilateral or unilateral hydronephrosis in both males and females with 23.5% and 12.5% prevalence, respectively...
December 23, 2016: Autoimmunity
Lidiane Zito Grund, Ivan Novaski, Valerie F Quesniaux, Bernhard Ryffel, Monica Lopes-Ferreira, Carla Lima
Interleukin (IL) 17A in chronic inflammation is also produced by innate immune cells as neutrophils. Mice with chronic humoral response induced by venom of Thalassophryne nattereri (VTn) proved to be a good tool for evaluating the impact of IL-17A on the development of long-lived plasma cells in the inflamed peritoneal cavity. Here, we report that VTn induces IL-17A production by neutrophils accumulating in the peritoneal cavity and triggers the extrusion of IL-17A along with neutrophil extracellular traps (NETs)...
December 23, 2016: Autoimmunity
Sajad Ahmad Dar, Shafiul Haque, Raju Kumar Mandal, Taru Singh, Mohd Wahid, Arshad Jawed, Aditya K Panda, Naseem Akhter, Mohtashim Lohani, Mohammed Yahya Areeshi, Gargi Rai, Shyama Datt, Sambit Nath Bhattacharya, Vishnampettai Ganapathysubramanian Ramachandran, Shukla Das
The association of interleukin-6 (IL-6)-174G > C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G > C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association...
December 23, 2016: Autoimmunity
Heena Mehta, Philippe-Olivier Goulet, Vinh Nguyen, Gemma Pérez, Martial Koenig, Jean-Luc Senécal, Marika Sarfati
DNA Topoisomerase I (TopoI) is a candidate autoantigen for diffuse cutaneous systemic sclerosis (dcSSc) associated with fatal lung disease. Dendritic cells (DCs) contribute to bleomycin-induced lung fibrosis. However, the possibility that TopoI-loaded DCs are involved in the initiation and/or perpetuation of dcSSc has not been explored. Here, we show that immunization with TopoI peptide-loaded DCs induces anti-TopoI autoantibody response and long-term fibrosis. Mice were repeatedly immunized with unpulsed DCs or DCs loaded with either TOPOIA or TOPOIB peptides, selected from different regions of TopoI...
November 3, 2016: Autoimmunity
Minori Saeki, Mikio Watanabe, Naoya Inoue, Ena Tokiyoshi, Yukina Takuse, Yuya Arakawa, Yoh Hidaka, Yoshinori Iwatani
Dicer and Drosha are RNase III enzymes that are necessary for the biogenesis of most miRNAs. However, there are no reports on the association of Dicer and Drosha with the pathogenesis of autoimmune thyroid disease (AITD). We genotyped DICER rs3742330A/G and rs1057035T/C as well as DROSHA rs644236C/T and rs10719C/T polymorphisms in 255 Hashimoto's disease (HD) patients, in 255 Graves' disease (GD) patients and in 128 healthy controls by the polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) method...
November 3, 2016: Autoimmunity
Davina Gorton, Suchandan Sikder, Natasha L Williams, Lisa Chilton, Catherine M Rush, Brenda L Govan, Madeleine W Cunningham, Natkunam Ketheesan
Rheumatic fever and rheumatic heart disease (RF/RHD) develop following repeated infection with group A streptococci (GAS). We used the Rat Autoimmune Valvulitis (RAV) model of RF/RHD to demonstrate that repetitive booster immunization with GAS-derived recombinant M protein (rM5) resulted in an enhanced anti-cardiac myosin antibody response that may contribute to the breaking of immune tolerance leading to RF/RHD and increased infiltration of heart valves by mononuclear cells. With each boost, more inflammatory cells were observed infiltrating heart tissue which could lead to severe cardiac damage...
December 2016: Autoimmunity
Peng Li, Xiu Wang, Meng-Qin Zhao, Lian-Ju Li, Chao Zhang, Bao-Zhu Li, Juan Liu, Xiao-Ke Yang, Rui-Xue Leng, Yin-Guang Fan, Hai-Feng Pan, Dong-Qing Ye
OBJECTIVES: Recent evidence has demonstrated that CD3ζ (also called CD247) play a vital role in multiple autoimmune diseases. In this study, we explored the association between CD247 gene single-nucleotide polymorphisms (SNPs) and rheumatoid arthritis (RA) in a Chinese Han population. We also evaluated the CD3ζ expression profile in peripheral blood mononuclear cells (PBMCs) from patients with RA and health controls. METHODS: Three CD247 polymorphisms (rs704853, rs1214611 and rs858554) were studied in 612 patients with RA and 848 controls in a Chinese population...
April 26, 2016: Autoimmunity
Heng Cao, Jin Lin, Weiqian Chen, Guanhua Xu, Chuanyin Sun
To determine the pathogenic role of adipokines, such as adiponectin and leptin, in rheumatoid arthritis (RA) by investigating whether serum levels of these adipokines correlated with disease activity in RA patients. Medline, Cochrane, EMBASE and Google Scholar were searched for studies published until 5 November 2015 reporting serum levels of leptin and adiponectin and measures of disease activity including DAS scores and radiographic progression scores (such as total change in SHS scores and number of erosions)...
September 30, 2016: Autoimmunity
Daniel Sánchez, Pavel Gregor, Karol Čurila, Iva Hoffmanová, Věra Hábová, Ludmila Tučková, Helena Tlaskalová-Hogenová
Distinct cellular level of the Ca(2+)-binding chaperone calreticulin (CRT) is essential for correct embryonal cardiac development and postnatal function. However, CRT is also a potential autoantigen eliciting formation of antibodies (Ab), whose role is not yet clarified. Immunization with CRT leads to cardiac injury, while overexpression of CRT in cardiomyocytes induces dilated cardiomyopathy (DCM) in animals. Hence, we analysed levels of anti-CRT Ab and calreticulin in the sera of patients with idiopatic DCM and hypertrophic cardiomyopathy (HCM)...
September 30, 2016: Autoimmunity
Sylvie Chabot, Fernando Alvarez, Abdelaziz Amrani, Idriss Djilali-Saiah
Identifying the type of diabetogenic CD8(+) T cells that initiate autoimmune diabetes (AID) is a critical step in designing appropriate strategies for the early detection of beta cell-directed autoimmunity and its progression to diabetes. We generated a novel double transgenic (Tg) mouse model on the naturally diabetes resistant C57Bl/6 background, co-expressing two transgenes including a specific TCR anti-lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) carried by CD8(+) T cells and LCMV-NP (as neo-self antigen) expressed by pancreatic beta cells...
September 2016: Autoimmunity
Zuzana Parackova, Jana Kayserova, Klara Danova, Kristyna Sismova, Eva Dudkova, Zdenek Sumnik, Stanislava Kolouskova, Jan Lebl, Katerina Stechova, Anna Sediva
T regulatory cells (Tregs) are essential for maintaining tolerance and preventing autoimmune diseases, such as type 1 diabetes (T1D). In our study, we investigated CD25 + FoxP3 + Tregs and thymic FoxP3 + Helios + Tregs in large cohorts of children with T1D at onset and with long-term T1D, and further in their relatives and healthy controls. We observed significantly decreased numbers of CD25 + FoxP3 + Tregs, but not FoxP3 + Helios + Tregs, in long-term patients compared with the control group and T1D onset...
August 25, 2016: Autoimmunity
Matthias Klein, Marc Schmalzing, Giovanni Almanzar, Sandrine Benoit, Henning Hamm, Hans-Peter Tony, Matthias Goebeler, Martina Prelog
Only limited attention has been paid to the role of CD8 + T cells in the etiopathogenesis and progression of systemic sclerosis (SSc). CD8 + T cells may have autoantigen-specific and pro-inflammatory but also immunomodulatory properties. To investigate the differentiation of CD8 + T cells, staining of cell surface factors and of chemokine receptors were performed. In addition, the cytokine-producing ability of circulating CD8 + T cells and their sensitivity to suppression by regulatory T cells (Tregs) were compared between patients with diffuse (dcSSc) or limited cutaneous SSc (lcSSc) and healthy individuals...
August 25, 2016: Autoimmunity
Jeffrey T Guptill, Vern C Juel, Janice M Massey, Amanda C Anderson, Manisha Chopra, John S Yi, Ehsanollah Esfandiari, Tim Buchanan, Bryan Smith, Paul Atherfold, Emma Jones, James F Howard
An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation...
August 11, 2016: Autoimmunity
Marc Rancier, Ines Zaaber, Maria G Stathopoulou, Jérôme Chatelin, Abdelsalam Saleh, Héla Marmouch, Said El Shamieh, Christine Masson, Helena Murray, John Lamont, Peter Fitzgerald, Silvia Mahjoub, Khaled Said, Besma Bel Haj Jrad Tensaout, Souhir Mestiri, Sophie Visvikis-Siest
The aim of this study was to assess the relationships between five different splice isoforms of VEGF mRNA and its plasma levels in individuals treated for autoimmune thyroid diseases (AITD); mainly Graves' disease (GD) and Hashimoto's thyroiditis (HT). In a population from Tunisia, levels of thyroid hormones and antibodies were quantified simultaneously with plasma VEGF and VEGF mRNA isoforms after a period of 6 months of patients' treatment. Plasma VEGF was measured in 110 AITD patients (21 GD and 89 HT patients)...
August 5, 2016: Autoimmunity
Kaori Uomori, Kazuhisa Nozawa, Keigo Ikeda, Kentaro Doe, Yusuke Yamada, Ayako Yamaguchi, Maki Fujishiro, Mikiko Kawasaki, Shinji Morimoto, Kenji Takamori, Iwao Sekigawa, Edward K L Chan, Yoshinari Takasaki
Novel autoantibodies against nuclear antigen of 14 kDa (NA-14)/Sjögren's syndrome nuclear antigen-1 (SSNA-1) are predominantly recognized in sera of patients with primary Sjögren's syndrome (pSS). However, the detailed characteristics of the anti-NA-14 antibody remain unknown. Here, we sought to clarify the characteristics of anti-SSNA-1/NA-14 antibodies and the mechanisms of autoantibody production using sera from patients with connective tissue diseases (including pSS), autoimmune sera reacting with standard autoantigens (SS-A/Ro and/or SS-B/La, ds DNA, Scl-70 and Jo-1), and normal healthy controls (NHCs)...
August 2016: Autoimmunity
Maiko Akahane, Mikio Watanabe, Naoya Inoue, Yumi Miyahara, Yuya Arakawa, Yuka Inoue, Yuka Katsumata, Yoh Hidaka, Yoshinori Iwatani
Chemokines induce leukocyte chemotaxis and contribute to chronic inflammation. To clarify the association between functional polymorphisms in genes encoding some chemokines and the pathogenesis of Autoimmune thyroid disease (AITD), we genotyped IL8 -251T/A, Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES) - 403G/A, -28C/G, MIG rs2276886G/A, IP10 -1596C/T, Monocyte Chemoattractant Protein1 (MCP1) - 2518G/A and IL16 -295T/C polymorphisms. We genotyped these polymorphisms using the PCR-RFLP method in 149 Graves' disease (GD) patients, including 59 patients with intractable GD and 53 patients with GD in remission, as well as 131 Hashimoto's disease (HD) patients, including 54 patients with severe HD, 46 patients with mild HD and 99 healthy controls...
August 2016: Autoimmunity
Christine S Haddad, Palash Bhattacharya, Khaled Alharshawi, Alejandra Marinelarena, Prabhakaran Kumar, Osama El-Sayed, Hatem A Elshabrawy, Alan L Epstein, Bellur S Prabhakar
Earlier, we have shown that GM-CSF derived bone marrow (BM) dendritic cells (G-BMDCs) can expand Foxp3(+) regulatory T-cells (Tregs) through a TCR-independent, but IL-2 dependent mechanism that required OX40L/OX40 interaction. While some reports have shown suppression of autoimmunity upon treatment with an OX40 agonist, others have shown exacerbation of autoimmune disease instead. To better understand the basis for these differing outcomes, we compared the effects of OX40L treatment in 6-week-old pre-diabetic and 12-week-old near diabetic NOD mice...
August 2016: Autoimmunity
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