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https://www.readbyqxmd.com/read/28546501/proteinase-3-the-odd-one-out-that-became-an-autoantigen
#1
REVIEW
Katherine R Martin, Véronique Witko-Sarsat
Neutrophils are critical in the defense against bacterial and fungal pathogens, and they also modulate the inflammatory process. The areas where neutrophils are studied have expanded from the restricted field of antibacterial defense to the modulation of inflammation and finally, to fine-tuning immune responses. As a result, recent studies have shown that neutrophils are implicated in several systemic autoimmune diseases, although exactly how neutrophils contribute to these diseases and the molecular mechanisms responsible are still under investigation...
May 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28546444/glial-fibrillary-acidic-protein-gfap-is-a-novel-biomarker-for-the-prediction-of-autoimmune-diabetes
#2
Zhengda Pang, Akifumi Kushiyama, Jiao Sun, Takako Kikuchi, Hiroki Yamazaki, Yasuhiko Iwamoto, Hiroshi Koriyama, Shota Yoshida, Munehisa Shimamura, Masayoshi Higuchi, Tomohiro Kawano, Yoichi Takami, Hiromi Rakugi, Ryuichi Morishita, Hironori Nakagami
Glial fibrillary acidic protein (GFAP) is expressed in peri-islet Schwann cells as well as in glia cells and has been reported to be an autoantigen candidate for type 1 diabetes mellitus (T1DM). We confirmed that the production of the autoantibodies GFAP and glutamic acid decarboxylase 65 (GAD65) was increased and inversely correlated with the concentration of secreted C peptide in female nonobese diabetic mice (T1DM model). Importantly, the development of T1DM in female nonobese diabetic mice at 30 wk of age was predicted by the positive GFAP autoantibody titer at 17 wk...
May 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28537230/-allergy-and-autoimmunity-molecular-diagnostics-therapy-and-presumable-pathogenesis
#3
A S Arefieva, O V Smoldovskaya, A A Tikhonov, A Yu Rubina
Allergic and autoimmune diseases represent immunopathological reactions of an organism to antigens. Despite that the allergy is a result of exaggerated immune response to foreign antigens (allergens) and autoimmune diseases are characterized by the pathological response to internal antigens (autoantigens), the underlying mechanisms of these diseases are probably common. Thus, both types of diseases represent variations in the hypersensitivity reaction. A large percentage of both the adult and pediatric population is in need of early diagnostics of these pathologies of the immune system...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28533781/myelin-oligodendrocyte-glycoprotein-deciphering-a-target-in-inflammatory-demyelinating-diseases
#4
REVIEW
Patrick Peschl, Monika Bradl, Romana Höftberger, Thomas Berger, Markus Reindl
Myelin oligodendrocyte glycoprotein (MOG), a member of the immunoglobulin (Ig) superfamily, is a myelin protein solely expressed at the outermost surface of myelin sheaths and oligodendrocyte membranes. This makes MOG a potential target of cellular and humoral immune responses in inflammatory demyelinating diseases. Due to its late postnatal developmental expression, MOG is an important marker for oligodendrocyte maturation. Discovered about 30 years ago, it is one of the best-studied autoantigens for experimental autoimmune models for multiple sclerosis (MS)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28533776/reactivity-to-novel-autoantigens-in-patients-with-coexisting-central-nervous-system-demyelinating-disease-and-autoimmune-thyroid-disease
#5
Judith M Greer, Simon Broadley, Michael P Pender
Several lines of evidence suggest a definite and unique link between CNS demyelinating diseases and autoimmune thyroid disease (AITD). The aim of the current study was to systematically compare the clinical and laboratory features of patients with coexistent AITD and CNS demyelinating disease with those of patients with just CNS demyelinating disease. Forty-four patients with coexisting CNS demyelinating disease and AITD were identified and their clinical and radiological features were recorded. Blood and DNA were collected and tested for HLA type and for the response of T cells and antibodies to a variety of antigens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28515156/anti-glomerular-basement-membrane-disease
#6
Stephen P McAdoo, Charles D Pusey
Anti-glomerular basement membrane (anti-GBM) disease is a rare small vessel vasculitis that affects the capillary beds of the kidneys and lungs. It is an archetypic autoimmune disease, caused by the development of directly pathogenic autoantibodies targeting a well characterized autoantigen expressed in the basement membranes of these organs, although the inciting events that induce the autoimmune response are not fully understood. The recent confirmation of spatial and temporal clustering of cases suggests that environmental factors, including infection, may trigger disease in genetically susceptible individuals...
May 17, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28486971/a-role-for-cathepsin-z-in-neuroinflammation-provides-mechanistic-support-for-an-epigenetic-risk-factor-in-multiple-sclerosis
#7
Euan R O Allan, Rhiannon I Campden, Benjamin W Ewanchuk, Pankaj Tailor, Dale R Balce, Neil T McKenna, Catherine J Greene, Amy L Warren, Thomas Reinheckel, Robin M Yates
BACKGROUND: Hypomethylation of the cathepsin Z locus has been proposed as an epigenetic risk factor for multiple sclerosis (MS). Cathepsin Z is a unique lysosomal cysteine cathepsin expressed primarily by antigen presenting cells. While cathepsin Z expression has been associated with neuroinflammatory disorders, a role for cathepsin Z in mediating neuroinflammation has not been previously established. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in both wildtype mice and mice deficient in cathepsin Z...
May 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28482118/autoantigens-adamtsl5-and-ll37-are-significantly-upregulated-in-active-psoriasis-and-localized-with-keratinocytes-dendritic-cells-and-other-leukocytes
#8
Judilyn Fuentes-Duculan, Kathleen M Bonifacio, Jason E Hawkes, Norma Kunjravia, Inna Cueto, Xuan Li, Juana Gonzalez, Sandra Garcet, James G Krueger
Psoriasis is a common immune-mediated disease that affects 2-4% of individuals in North America and Europe. In the past decade, advances in research have led to an improved understanding of immune pathways involved in the pathogenesis of psoriasis and has spurred the development of targeted therapeutics. Recently, three psoriasis autoantigens have been described: cathelicidin (LL37), a disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5), and lipid antigens generated by phospholipase A2 (PLA2) group IVD (PLA2G4D)...
May 8, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28476558/low-expression-of-complement-inhibitory-protein-cd59-contributes-to-humoral-autoimmunity-against-astrocytes
#9
Zhen Wang, Wen Guo, Yuanchu Liu, Ye Gong, Xiaoli Ding, Kaibin Shi, Rodolfo Thome, Guang-Xian Zhang, Fu-Dong Shi, Yaping Yan
Neuromyelitis optica spectrum disorder is primarily an anti-aquaporin 4 autoantibody-mediated, central nervous system-restricted channelopathy. Patients frequently develop central nervous system-restricted lesions even though autoantigen aquaporin 4 in neuromyelitis optica spectrum disorder is broadly distributed in the central nervous system and peripheral organs. The cause of such tissue-specific immune response remains largely unknown. We confirmed here that CD59, an inhibitory regulator of the complement membrane attack complex, is expressed and co-localized with aquaporin 4 in peripheral organs but is only minimally expressed in astrocytes in the central nervous system...
May 2, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28474886/multivalent-soluble-antigen-arrays-exhibit-high-avidity-binding-and-modulation-of-b-cell-receptor-mediated-signaling-to-drive-efficacy-against-experimental-autoimmune-encephalomyelitis
#10
Brittany L Hartwell, Chad J Pickens, Martin Leon, Cory Berkland
A pressing need exists for antigen-specific immunotherapies (ASIT) that induce selective tolerance in autoimmune disease while avoiding deleterious global immunosuppression. Multivalent soluble antigen arrays (SAgAPLP:LABL), consisting of a hyaluronic acid (HA) linear polymer backbone cografted with multiple copies of autoantigen (PLP) and cell adhesion inhibitor (LABL) peptides, are designed to induce tolerance to a specific multiple sclerosis (MS) autoantigen. Previous studies established that hydrolyzable SAgAPLP:LABL, employing a degradable linker to codeliver PLP and LABL, was therapeutic in experimental autoimmune encephalomyelitis (EAE) in vivo and exhibited antigen-specific binding with B cells, targeted the B cell receptor (BCR), and dampened BCR-mediated signaling in vitro...
May 17, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28474508/complete-freund-s-adjuvant-induces-experimental-autoimmune-myocarditis-by-enhancing-il-6-production-during-initiation-of-the-immune-response
#11
Jillian A Fontes, Jobert G Barin, Monica V Talor, Natalie Stickel, Julie Schaub, Noel R Rose, Daniela Čiháková
INTRODUCTION: Complete Freund's Adjuvant (CFA) emulsified with an antigen is a widely used method to induce autoimmune disease in animal models, yet the contribution of CFA to the immune response is not well understood. We compared the effectiveness of CFA with Incomplete Freund's Adjuvant (IFA) or TiterMax Gold Adjuvant (TMax) in experimental autoimmune myocarditis (EAM) in male mice. METHODS: EAM was induced in A/J, BALB/c, and IL6KO BALB/c male mice by injection of the myocarditogenic peptide in CFA, IFA, or TMax on days 0 and 7...
June 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28472610/nature-functions-and-clinical-implications-of-igg4-autoantibodies-in-systemic-lupus-erythematosus-and-rheumatoid-arthritis
#12
Qingjun Pan, Qiaofen Lan, Yanxia Peng, Jun Cai, Jian Zheng, Carol Dickerson, Haiyan Xiao, Hua-Feng Liu
Protective autoantibodies in homeostasis, clinical relevance, and therapeutic potential have gained wide attention. Recent studies showed that IgG4 autoantibodies play crucial roles in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In one aspect, IgG4 autoantibodies can bind autoantigens in competition with other classes of immunoglobulins (e.g., IgG1, IgG2a) to form non-inflammatory immune-complexes (ICs), which have a limited ability to induce immune responses because of the low affinity of IgG4 for both Fc receptors and the C1 complement molecule, resulting in reduced inflammatory response in SLE and RA...
March 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28467202/a-rationally-designed-peptide-ia-2-p2-against-type-1-diabetes-in-streptozotocin-induced-diabetic-mice
#13
Lili Shen, Shiping Lu, Dongcheng Huang, Guoliang Li, Kunfeng Liu, Rongyue Cao, Li Zong, Liang Jin, Jie Wu
Recent studies have investigated the potential of type 1 diabetes mellitus-related autoantigens, such as heat shock protein 60, to induce immunological tolerance or to suppress the immune response. A functional 24-residue peptide derived from heat shock protein 60 (P277) has shown anti-type 1 diabetes mellitus potential in experimental animals and in clinical studies, but it also carries a potential atherogenic effect. In this study, we have modified P277 to retain an anti-type 1 diabetes mellitus effect and minimize the atherogenic potential by replacing the P277 B epitope with another diabetes-associated autoantigen, insulinoma antigen-2 (IA-2), to create the fusion peptide IA-2-P2...
May 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28463230/cd1b-autoreactive-t-cells-contribute-to-hyperlipidemia-induced-skin-inflammation-in-mice
#14
Sreya Bagchi, Ying He, Hong Zhang, Liang Cao, Ildiko Van Rhijn, D Branch Moody, Johann E Gudjonsson, Chyung-Ru Wang
A large proportion of human T cells are autoreactive to group 1 CD1 proteins, which include CD1a, CD1b, and CD1c. However, the physiological role of the CD1 proteins remains poorly defined. Here, we have generated a double-transgenic mouse model that expresses human CD1b and CD1c molecules (hCD1Tg) as well as a CD1b-autoreactive TCR (HJ1Tg) in the ApoE-deficient background (hCD1Tg HJ1Tg Apoe-/- mice) to determine the role of CD1-autoreactive T cells in hyperlipidemia-associated inflammatory diseases. We found that hCD1Tg HJ1Tg Apoe-/- mice spontaneously developed psoriasiform skin inflammation characterized by T cell and neutrophil infiltration and a Th17-biased cytokine response...
May 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28456018/unique-features-in-the-presentation-of-insulin-epitopes-in-autoimmune-diabetes-an-update
#15
REVIEW
Xiaoxiao Wan, Emil R Unanue
Although an autoimmune disease involves diverse self-antigens, the initiation stage may require recognition of a limited number. This concept is verified in the non-obese diabetic (NOD) mouse model of autoimmune diabetes, in which strong evidence points to insulin as the prime antigen. The NOD mouse bears the I-A(g7) class II-MHC molecules (MHCII) that share common biochemical features and peptidome selection with the human diabetes-susceptible HLA-DQ8. Furthermore, both NOD mice and patients with type 1 diabetes (T1D) display an early appearance of insulin autoantibodies (IAAs) and subsequent insulin-reactive T cell infiltration into the islets...
April 26, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28455372/regulation-of-neuromuscular-junction-organization-by-rab2-and-its-effector-ica69-in-drosophila
#16
Bhagaban Mallik, Manish Kumar Dwivedi, Zeeshan Mushtaq, Manisha Kumari, Praveen Kumar Verma, Vimlesh Kumar
Mechanisms underlying synaptic differentiation, which involves neuronal membrane and cytoskeletal remodeling, are not completely understood. We performed a targeted RNAi-mediated screen of Drosophila BAR-domain proteins and identified islet cell autoantigen 69 kDa (dICA69) as one of the key regulators of morphological differentiation of larval neuromuscular junction (NMJ). We show that Drosophila ICA69 colocalizes with α-Spectrin at the NMJ. The conserved N-BAR domain of dICA69 deforms liposomes in vitro Full length and ICAC but not the N-BAR domain of dICA69 induces filopodia in cultured cells...
April 28, 2017: Development
https://www.readbyqxmd.com/read/28450863/the-proteasome-inhibitor-bortezomib-controls-indoleamine-2-3-dioxygenase-1-breakdown-and-restores-immune-regulation-in-autoimmune-diabetes
#17
Giada Mondanelli, Elisa Albini, Maria T Pallotta, Claudia Volpi, Lucienne Chatenoud, Chantal Kuhn, Francesca Fallarino, Davide Matino, Maria L Belladonna, Roberta Bianchi, Carmine Vacca, Silvio Bicciato, Louis Boon, Giovanni Ricci, Ursula Grohmann, Paolo Puccetti, Ciriana Orabona
Bortezomib (BTZ) is a first-in-class proteasome inhibitor approved for the therapy of multiple myeloma that also displays unique regulatory activities on immune cells. The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan metabolizing enzyme exerting potent immunoregulatory effects when expressed in dendritic cells (DCs), the most potent antigen-presenting cells capable of promoting either immunity or tolerance. We previously demonstrated that, in inflammatory conditions, IDO1 is subjected to proteasomal degradation in DCs, turning these cells from immunoregulatory to immunostimulatory...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28429225/design-of-chemical-conjugate-for-targeted-therapy-of-multiple-sclerosis-based-of-constant-fragment-of-human-antibody-heavy-chain-and-peptoid-analog-of-autoantigen-mog35-55
#18
Y A Lomakin, A V Stepanov, D S Balabashin, N A Ponomarenko, I V Smirnov, A A Belogurov
Elimination of B cells producing autoantibodies to neuroantigens is considered as beneficial in the treatment of multiple sclerosis. Myelin oligodendrocyte glycoprotein (MOG) is a significant autoantigen in multiple sclerosis. It was shown that MOG-like peptoid AMogP3 can bind autoantibodies produced by pathological lymphocytes. We propose a structure of an innovative drug for targeted elimination of the pool of autoreactive B cells responsible for multiple sclerosis pathogenesis; this compound is a complex of peptoid AMogP3 with Fc fragment of human immunoglobulin...
April 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28427776/autoantibody-biomarkers-for-the-detection-of-serous-ovarian-cancer
#19
Benjamin A Katchman, Diego Chowell, Garrick Wallstrom, Allison F Vitonis, Joshua LaBaer, Daniel W Cramer, Karen S Anderson
Objective The purpose of this study was to identify a panel of novel serum tumor antigen-associated autoantibody (TAAb) biomarkers for the diagnosis of high-grade serous ovarian cancer. METHODS: To detect TAAb we probed high-density programmable protein microarrays (NAPPA) containing 10,247 antigens with sera from patients with serous ovarian cancer (n=30 cases/30 healthy controls) and measured bound IgG. We identified 735 promising tumor antigens and evaluated these with an independent set of serous ovarian cancer sera (n=30 cases/30 benign disease controls/30 healthy controls)...
April 17, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28417151/a-review-of-the-role-and%C3%A2-clinical-utility-of-anti-ro52-trim21-in-systemic-autoimmunity
#20
REVIEW
Adrian Y S Lee
Anti-Ro52/tripartite motif-containing 21 (TRIM21) is a ubiquitous antibody found in a number of systemic autoimmune conditions including Sjögren's syndrome, systemic lupus erythematosus and systemic sclerosis, appearing in about half of these patients. Once coupled with its closely related antibody, anti-Ro60 as the anti-SSA antibody, anti-Ro52 is emerging as a unique antibody with direct pathogenic disease involvement and distinct clinical properties. As a result, recent attention has turned to this antibody and its clinical associations and utility...
April 17, 2017: Rheumatology International
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