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https://www.readbyqxmd.com/read/29053992/biomarker-guided-stratification-of-autoimmune-patients-for-biologic-therapy
#1
REVIEW
Sabine Ivison, Christine des Rosiers, Sylvie Lesage, John D Rioux, Megan K Levings
Autoimmunity results from an intersection of genetic and environmental factors that cause patient-specific perturbations in immune homeostasis. Defining autoimmunity-associated genetic factors has led to mechanistic insight into underlying etiologies, and the development of many biologic therapies that target the immune system. However, biomarker-informed pairing of patients with optimal biologic therapy is lacking. Here, we discuss platforms commonly used to find biomarkers that predict response to biologic therapy in autoimmunity and highlight recent biomarker discoveries...
October 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29053971/a-gut-microbial-mimic-that-hijacks-diabetogenic-autoreactivity-to-suppress-colitis
#2
Roopa Hebbandi Nanjundappa, Francesca Ronchi, Jinguo Wang, Xavier Clemente-Casares, Jun Yamanouchi, Channakeshava Sokke Umeshappa, Yang Yang, Jesús Blanco, Helena Bassolas-Molina, Azucena Salas, Hamza Khan, Robyn M Slattery, Madeleine Wyss, Catherine Mooser, Andrew J Macpherson, Laura K Sycuro, Pau Serra, Derek M McKay, Kathy D McCoy, Pere Santamaria
The gut microbiota contributes to the development of normal immunity but, when dysregulated, can promote autoimmunity through various non-antigen-specific effects on pathogenic and regulatory lymphocytes. Here, we show that an integrase expressed by several species of the gut microbial genus Bacteroides encodes a low-avidity mimotope of the pancreatic β cell autoantigen islet-specific glucose-6-phosphatase-catalytic-subunit-related protein (IGRP206-214). Studies in germ-free mice monocolonized with integrase-competent, integrase-deficient, and integrase-transgenic Bacteroides demonstrate that the microbial epitope promotes the recruitment of diabetogenic CD8+ T cells to the gut...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29053038/igg4-related-orbital-disease-masquerading-as-thyroid-eye-disease-vice-versa-or-both
#3
Joyce Khandji, Ashley A Campbell, Alison B Callahan, Portia Sirinek, Michael Kazim
A 40 year-old male presented after one year of unilateral, progressive, steroid-responsive, orbital inflammatory disease causing proptosis, extraocular muscle (EOM) restriction, and compressive optic neuropathy. The development of anti-thyroidal antibodies prompted the diagnosis of thyroid eye disease (TED); however, the prolonged active phase, remarkable reversibility of ophthalmic features with high-dose corticosteroids, unilaterally of disease, uncharacteristic EOM involvement (including both obliques), and the absence of autoimmune thyroid disease provoked consideration of alternative diagnoses...
October 20, 2017: Orbit
https://www.readbyqxmd.com/read/29053037/possible-autoantibody-negative-limbic-encephalitis-after-anterior-temporal-lobectomy-for-hippocampal-sclerosis
#4
Sara Casciato, Alfredo D'Aniello, Addolorata Mascia, Pier Paolo Quarato, Marco De Risi, Liliana G Grammaldo, Vincenzo Esposito, Marco Zoccarato, Giancarlo Di Gennaro
Amnestic syndromes are acknowledged to be associated to bilateral hippocampal damage. We briefly report the case of a young man who underwent anterior left temporal lobectomy for a medically refractory temporal lobe epilepsy due to hippocampal sclerosis with an excellent seizure and neuropsychological outcome. Approximately 10 years later, he presented with a subacute severe global amnesia and MRI findings of a damage involving the contralateral mesial temporal lobe structures. A diagnosis of a possible autoimmune encephalitis was made...
October 20, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29052687/association-between-early-life-antibiotic-use-and-the-risk-of-islet-or-celiac-disease-autoimmunity
#5
Kaisa M Kemppainen, Kendra Vehik, Kristian F Lynch, Helena Elding Larsson, Ronald J Canepa, Ville Simell, Sibylle Koletzko, Edwin Liu, Olli G Simell, Jorma Toppari, Anette G Ziegler, Marian J Rewers, Åke Lernmark, William A Hagopian, Jin-Xiong She, Beena Akolkar, Desmond A Schatz, Mark A Atkinson, Martin J Blaser, Jeffrey P Krischer, Heikki Hyöty, Daniel Agardh, Eric W Triplett
Importance: Evidence is lacking regarding the consequences of antibiotic use in early life and the risk of certain autoimmune diseases. Objective: To test the association between early-life antibiotic use and islet or celiac disease (CD) autoimmunity in genetically at-risk children prospectively followed up for type 1 diabetes (T1D) or CD. Design, Setting, and Participants: HLA-genotyped newborns from Finland, Germany, Sweden, and the United States were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY) study between November 20, 2004, and July 8, 2010...
October 9, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/29052263/ang-ii-ccr2-5-axis-dependent-monocyte-macrophage-recruitment-contributed-to-experimental-autoimmune-myocarditis-progression
#6
Hongxiang Lu, Gangjun Zong, Shanshan Zhou, Yuanyuan Jiang, Rong Chen, Zhaoliang Su, Yan Wu
Angiotensin II (ANG II) plays critical roles in modulation of circulatory homeostasis and activation of innate and adaptive immunity. Furthermore, ANG II has also been implicated in several mouse models of autoimmune disease. However, it remains incompletely clear how ANG II regulates macrophage and involves in experimental autoimmune myocarditis (EAM) development. Therefore, the present work was to address the above question and to explore the possible mechanism. The BALB/c mice were used to induce EAM model...
October 20, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/29052174/phagocytosis-deficiency-of-macrophages-in-nod-h-2-h4-mice-accelerates-the-severity-of-iodine-induced-autoimmune-thyroiditis
#7
Xue He, Chuhui Xiong, Aihua Liu, Wei Zhao, Xinghai Xia, Shiqiao Peng, Chenyan Li, Mi Zhou, Yushu Li, Xiaoguang Shi, Zhongyan Shan, Weiping Teng
Apoptosis occurs in many autoimmune diseases. Excess iodine induces thyrocyte apoptosis and increases the incidence and prevalence of autoimmune thyroiditis (AIT). However, the sequence of events between the appearance of thyrocyte apoptosis and the occurrence of thyroiditis remains uncharacterized. Furthermore, few studies have investigated the role of macrophage phagocytosis in the development of AIT. Therefore, we evaluated the relationship between apoptosis and inflammatory infiltration in NOD.H-2(h4) mouse thyroids by comparing the sequence of events in tissue samples...
October 20, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/29052141/murine-gammaherpesvirus-68-a-small-animal-model-for-gammaherpesvirus-associated-diseases
#8
Sihan Dong, J Craig Forrest, Xiaozhen Liang
Murine gammaherpesvirus 68 (MHV68) is a naturally occurring pathogen of murid rodents that is genetically related to the human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV). Viral, immunologic, and disease parameters following experimental infection of laboratory mice with MHV68 closely resemble what occurs during primary EBV infection of humans, which suggests that MHV68 infection of mice offers a small animal model to study in general the pathogenesis of gammaherpesvirus infections...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29051989/a-randomized-phase-i-study-to-evaluate-the-safety-tolerability-pharmacokinetics-and-food-effect-of-iguratimod-in-healthy-adult-volunteers
#9
Feng Xiao, Feng Zhang, Ling-Ling Zhang, Wei Wei
OBJECTIVE: The aim of this study was to investigate the safety, maximum tolerated dose and pharmacokinetics (PK) of iguratimod and the effect of food on PK parameters in healthy adult volunteers. METHODS: This phase 1 study consisted of four parts. Part 1 was a single-ascending dose (3.125, 6.25, 12.5, 25, 50, 75 mg) study to assess the maximum tolerated dose and safety of iguratimod. Part 2 was a single-ascending dose study to analyze the pharmacokinetic (PK) parameters of iguratimod; subjects were divided into three groups, with each group receiving iguratimod at a different dose (25, 50 or 75 mg)...
October 19, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29051973/igra-testing-in-patients-with-immune-mediated-inflammatory-diseases-which-factors-influence-the-results
#10
Juan González-Moreno, Mercedes García-Gasalla, Inés Losada-López, Carmen Cifuentes Luna, Isabel Mir Viladrich, Victoria Fernández-Baca, Araceli Serrano, Antonio Juan Mas, Joan Riera-Oliver, Antoni Payeras Cifre
Diagnosis of latent tuberculosis infection in patients with immune-mediated inflammatory chronic diseases (IMIDs) can be challenged as diagnostic test reliability could be impaired by immunosuppression. We retrospectively analyzed the Quantiferon Gold-Test in-Tube (QFT-G-IT) results of all patients with IMIDs seen at the Department of Internal Medicine of Son Llàtzer Hospital, Palma de Mallorca (Spain), looking for the factors related to QFT-G-IT indeterminate results. During the study period (2008-2015), 520 patients met the inclusion criteria...
October 19, 2017: Rheumatology International
https://www.readbyqxmd.com/read/29051963/applications-of-particulate-oxygen-generating-substances-pogs-in-the-bioartificial-pancreas
#11
John P McQuilling, Sivanandane Sittadjody, Samuel Pendergraft, Alan C Farney, Emmanuel C Opara
Type-1 Diabetes (T1D) is a devastating autoimmune disorder which results in the destruction of beta cells within the pancreas. A promising treatment strategy for T1D is the replacement of the lost beta cell mass through implantation of immune-isolated microencapsulated islets referred to as the bioartificial pancreas. The goal of this approach is to restore blood glucose regulation and prevent the long-term comorbidities of T1D without the need for immunosuppressants. A major requirement in the quest to achieve this goal is to address the oxygen needs of islet cells...
October 20, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29051892/autoimmune-pancreatitis-type-2-case-report
#12
Chidinma Onweni, Harika Balagoni, Jennifer M Treece, Emmanuel Addo Yobo, Archi Patel, Jennifer Phemister, Manoj Srinath, Mark F Young
A middle-aged man presents with acute pancreatitis of unknown etiology and is found to have a presentation consistent with the diagnosis of type 2 autoimmune pancreatitis (AIP). AIP is a group of rare heterogeneous diseases that are challenging to diagnose. There are 2 types of AIP. Type 1 disease is the more common worldwide than type 2 AIP. While type 1 AIP is associated with IgG4-positive antibodies, type 2 AIP is IgG4 antibody negative. Both types of AIP are responsive to corticosteroid treatment. Although type 1 AIP has more extrapancreatic manifestations and more commonly relapses, this is a case of a patient with type 2 AIP with inflammatory bowel disease and relapsing course...
October 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29051891/scleroderma-renal-crisis-in-mixed-connective-tissue-disease-with-full-renal-recovery-within-3-months-a-case-report-with-expanding-treatment-modalities-to-treat-each-clinical-sign-as-an-independent-entity
#13
Jordana Cheta, Suresh Rijhwani, Harlan Rust
Mixed connective tissue disease (MCTD) is a rheumatologic overlap syndrome that can present with symptoms of systemic lupus erythematous, scleroderma, and polymyositis. A severe but rare complication that can occur in MCTD is scleroderma renal crisis. With multiple poor prognostic indicators, the renal outcome is usually poor. The clinical and histological picture is one of a thrombotic microangiopathy. Clinical suspicion has to be high for additional thrombotic or autoimmune processes coexisting due to associated morbidity...
October 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29051789/novel-strategies-and-therapeutic-options-for-the-management-of-primary-biliary-cholangitis
#14
REVIEW
Amardeep Khanna, David E Jones
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. It has a varied course of progression ranging from being completely asymptomatic to aggressive disease leading to cirrhosis and resulting in liver transplantation. In addition, symptoms can be debilitating and can have a major impact on quality of life. For decades, there was only one anti-cholestatic agent available to target this disease and that was only effective in around half of patients, with little or no effect on symptoms. With increasing understanding of the pathogenic mechanisms of PBC and potential targets for drug treatment, pharmaceutical companies have shown a greater interest in this rare disease...
October 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29051763/il-12p35-inhibits-neuroinflammation-and-ameliorates-autoimmune-encephalomyelitis
#15
Jin Kyeong Choi, Ivy M Dambuza, Chang He, Cheng-Rong Yu, Anita N Uche, Mary J Mattapallil, Rachel R Caspi, Charles E Egwuagu
Multiple sclerosis (MS) is an inflammatory demyelinating disease in which cytokines produced by immune cells that infiltrate the brain and spinal cord play a central role. We show here that the IL-12p35, the alpha subunit of IL-12 or IL-35 cytokine, might be an effective biologic for suppressing neuroinflammatory responses and ameliorating the pathology of experimental autoimmune encephalomyelitis (EAE), the mouse model of human MS. We further show that IL-12p35 conferred protection from neuropathy by inhibiting the expansion of pathogenic Th17 and Th1 cells and inhibiting trafficking of inflammatory cells into the brain and spinal cord...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29051105/nicotine-and-autoimmunity-the-lotus-flower-in-tobacco
#16
REVIEW
João Pedro Gomes, Abdulla Watad, Yehuda Shoenfeld
Nicotine, the major component of cigarettes, has demonstrated conflicting impact on the immune system: some authors suggest that increases pro-inflammatory cytokines and provokes cellular apoptosis of neutrophils, releasing intracellular components that act as auto-antigens; others claimed that nicotine has a protective and anti-inflammatory effects, especially by binding to α7 subunit of nicotinic acetylcholine receptors. The cholinergic pathway contributes to an anti-inflammatory environment characterized by increasing T regulatory cells response, down-regulating of pro-inflammatory cytokines and a pro-inflammatory cells apoptosis...
October 16, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29051099/hyperglycemia-induced-reactive-species-trigger-structural-changes-in-human-serum-albumin-of-type-1-diabetic-subjects
#17
Zarina Arif, Km Neelofar, Mir Yasir Arfat, Asif Zaman, Akhlas Tarannum, Iffat Parveen, Shafeeque Ahmad, Md Adnan Khan, Asim Badar, Shireen Naaz Islam
Chronic oxidative stress fuels pathogenesis of a large set of diseases. Oxidative stress is the cause and consequence of numerous diseases including type 1 diabetes mellitus (T1DM), in which there is selective destruction of insulin producing pancreatic β-cells. Studies have documented that hyperglycemia produces profound stress. In vivo production of numerous reactive oxygen, nitrogen, chlorine species and lipid/sugar oxidation products are result of persistent hyperglycemia. Post-translational modifications by reactive species may create new antigenic epitopes and play a role in the development of autoimmune response...
October 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29051068/genotoxic-effect-and-antigen-binding-characteristics-of-sle-auto-antibodies-to-peroxynitrite-modified-human-dna
#18
Md Asad Khan, Khursheed Alam, Syed Hassan Mehdi, M Moshahid A Rizvi
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by auto-antibodies against native deoxyribonucleic acid after modification and is one of the reasons for the development of SLE. Here, we have evaluated the structural perturbations in human placental DNA by peroxynitrite using spectroscopy, thermal denaturation and high-performance liquid chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional oxidative/nitrative agent that is produced both endogenously and exogenously...
October 16, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29051008/dna-recombination-defects-in-kuwait-clinical-immunologic-and-genetic-profile
#19
Waleed Al-Herz, Michel J Massaad, Janet Chou, Luigi D Notarangelo, Raif S Geha
Defects in DNA Recombination due to mutations in RAG1/2 or DCLRE1C result in combined immunodeficiency (CID) with a range of disease severity. We present the clinical, immunologic and molecular characteristics of 21 patients with defects in RAG1, RAG2 or DCLRE1C, who accounted for 24% of combined immune deficiency cases in the Kuwait National Primary Immunodeficiency Disorders Registry. The distribution of the patients was as follow: 8 with RAG1 deficiency, 6 with RAG2 deficiency and 7 with DCLRE1C deficiency...
October 16, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29050994/celiac-disease-or-positive-tissue-transglutaminase-antibodies-in-patients-undergoing-renal-biopsies
#20
Rakel Nurmi, Martti Metso, Ilkka Pörsti, Onni Niemelä, Heini Huhtala, Jukka Mustonen, Katri Kaukinen, Satu Mäkelä
BACKGROUND: An association between celiac disease and renal diseases has been suggested, but the results are controversial. AIMS: To investigate the prevalence of celiac disease autoimmunity among individuals undergoing renal biopsies and to evaluate whether co-existent celiac autoimmunity influences the clinical outcome of the renal disease. METHODS: The prevalence of celiac autoimmunity (previous diagnosis of celiac disease or positive tissue transglutaminase antibodies) was determined in 827 consecutive patients undergoing kidney biopsies due to clinical indications...
October 5, 2017: Digestive and Liver Disease
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