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Asthma biological therapies and autoimmune disease

Seung-Hyung Kim, Evelyn Saba, Bok-Kyu Kim, Won-Kyung Yang, Yang-Chun Park, Han Jae Shin, Chang Kyun Han, Young Cheol Lee, Man Hee Rhee
Regulatory T cells play an important role in autoimmunity and have been shown to exert anti-inflammatory effects in allergic asthma. Mouse model of airway inflammation was used to examine the suppressive activity of luteolin-induced CD4+ CD25+ regulatory T cells (Tregs) in vivo. In this study, BALB/c mice were sensitized with ovalbumin antigen (OVA) by aerosol challenge. Then, various biological processes were examined, including airway eosinophilia; mucus hypersecretion; elevation of OVA-specific IgE, expression of Th2 cytokines and chemokine levels; expression of eotaxin 2 and CCR3; and airway hyper responsiveness (AHR)...
February 5, 2018: European Journal of Pharmacology
Wei Gao, Ye Xiong, Qiang Li, Hong Yang
The recognition of invading pathogens and endogenous molecules from damaged tissues by toll-like receptors (TLRs) triggers protective self-defense mechanisms. However, excessive TLR activation disrupts the immune homeostasis by sustained pro-inflammatory cytokines and chemokines production and consequently contributes to the development of many inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE), infection-associated sepsis, atherosclerosis, and asthma. Therefore, inhibitors/antagonists targeting TLR signals may be beneficial to treat these disorders...
2017: Frontiers in Physiology
Joachim Sennekamp, Hans-Peter Seelig
BACKGROUND: A 42-year old male patient with anamnesis of bronchial asthma presented himself with exertional dyspnea. High titer antibodies of cytoplasmic pattern in the indirect immunofluorescence test (IIFT) on HEp-2cells, not attributable to common specificities like anti-tRNA-synthetases, anti-signal recognition particle (SRP) or anti-ribosomal proteins (RPs) prompted the molecular biological approach for determination of antigen specificity. In-depth investigation of the patient's clinical settings revealed a lymphocyte predominant Hodgkin's lymphoma, which could be brought to complete remission by chemotherapy...
August 1, 2016: Clinical Laboratory
Manali Mukherjee, Hui Fang Lim, Sruthi Thomas, Douglas Miller, Melanie Kjarsgaard, Bruce Tan, Roma Sehmi, Nader Khalidi, Parameswaran Nair
BACKGROUND: Anti-interleukin (IL)-5 monoclonal antibodies as an eosinophil-depleting strategy is well established, with Mepolizumab being the first biologic approved as an adjunct treatment for severe eosinophilic asthma. CASE PRESENTATION: A 62-year old woman diagnosed with severe eosinophilic asthma showed poor response to Mepolizumab therapy (100 mg subcutaneous dose/monthly) and subsequent worsening of symptoms. The treatment response to Mepolizumab was monitored using both blood and sputum eosinophil counts...
2017: Allergy, Asthma, and Clinical Immunology
Scott C Kachlany
Alopecia areata is an autoimmune condition where activated, pro-inflammatory white blood cells (WBCs) attack the hair follicles, resulting in hair loss. Migration of these activated WBCs from the blood stream and into the follicle tissue requires interaction between the integrin, lymphocyte function-associated antigen-1 (LFA-1) on WBCs, and ICAM-1 on vascular endothelial cells. High levels of active LFA-1 are uniquely expressed on WBCs that are involved in autoimmune and inflammatory conditions. The natural biologic agent LtxA (Leukothera) preferentially targets and depletes disease activated and malignant WBCs by binding to active LFA-1...
November 2015: Journal of Investigative Dermatology. Symposium Proceedings
Victoria Richmond, Flavia M Michelini, Carlos A Bueno, Laura E Alché, Javier A Ramírez
Tumor necrosis factor (TNF, TNF-α, cachectin) is a pleiotropic, proinflammatory cytokine with multiple biological effects, many of which are not yet fully understood. Although TNF was initially described as an anti-tumor agent more than three decades ago, current knowledge places it central to immune system homeostasis. TNF plays a critical role in host defense against infection, as well as an inhibitory role in autoimmune disease. However, TNF overproduction generates deleterious effects by inducing the transcription of genes involved in acute and chronic inflammatory responses including asthma, rheumatoid arthritis, Crohn's disease, and psoriasis...
2015: Current Medicinal Chemistry
Mark M Perry, Ian M Adcock, Kian Fan Chung
PURPOSE OF REVIEW: MicroRNAs (miRNAs) modulate gene transcription in response to environmental stressors and other stimuli. A role for miRNAs in inflammation and immunity has been demonstrated and further evidence suggests that miRNAs also play a role in allergic asthma. RECENT FINDINGS: Studies investigating the differential expression of miRNAs in biological fluids between asthma patients and controls have been published, as have their role in immune cell subsets...
April 2015: Current Opinion in Allergy and Clinical Immunology
Pamela M K Lutalo, David P D'Cruz
The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA) constitute a wide spectrum of clinical manifestations of systemic vasculitis which may range from limited disease to organ or life-threatening disease. The introduction of biologics for the management of severe ANCA-associated vasculitis and severe, relapsing disease refractory to conventional immunosuppressants, has significantly improved the clinical prognosis of these autoimmune disorders...
August 2015: International Immunopharmacology
Jeffrey A Bluestone, Eleonora Trotta, Daqi Xu
INTRODUCTION: Immune tolerance remains the holy grail of therapeutic immunology in the fields of organ and tissue transplant rejection, autoimmune diseases, and allergy and asthma. We have learned that FoxP3(+)CD4(+) regulatory T cells play a vital role in both the induction and maintenance of self-tolerance. AREAS COVERED: In this opinion piece, we highlight regulatory T cells (Treg) cell biology and novel immune treatments to take advantage of these cells as potent therapeutics...
2015: Expert Opinion on Therapeutic Targets
Linda J Wammes, Harriet Mpairwe, Alison M Elliott, Maria Yazdanbakhsh
Deworming is rightly advocated to prevent helminth-induced morbidity. Nevertheless, in affluent countries, the deliberate infection of patients with worms is being explored as a possible treatment for inflammatory diseases. Several clinical trials are currently registered, for example, to assess the safety or efficacy of Trichuris suis ova in allergies, inflammatory bowel diseases, multiple sclerosis, rheumatoid arthritis, psoriasis, and autism, and the Necator americanus larvae for allergic rhinitis, asthma, coeliac disease, and multiple sclerosis...
November 2014: Lancet Infectious Diseases
Christopher Chang
The care of patients with respiratory diseases has improved vastly in the past 50 years. In spite of that, there are still massive challenges that have not been resolved. Although the incidence of tuberculosis has decreased in the developed world, it is still a significant public health problem in the rest of the world. There are still over 2 million deaths annually from tuberculosis, with most of these occurring in the developing world. Even with the development of new pharmaceuticals to treat tuberculosis, there is no indication that the disease will be eradicated...
December 2013: Clinical Reviews in Allergy & Immunology
Gabriella Miklossy, Tyvette S Hilliard, James Turkson
The signal transducer and activator of transcription (STAT) proteins have important roles in biological processes. The abnormal activation of STAT signalling pathways is also implicated in many human diseases, including cancer, autoimmune diseases, rheumatoid arthritis, asthma and diabetes. Over a decade has passed since the first inhibitor of a STAT protein was reported and efforts to discover modulators of STAT signalling as therapeutics continue. This Review discusses the outcomes of the ongoing drug discovery research endeavours against STAT proteins, provides perspectives on new directions for accelerating the discovery of drug candidates, and highlights the noteworthy candidate therapeutics that have progressed to clinical trials...
August 2013: Nature Reviews. Drug Discovery
Fabien B Vincent, Damien Saulep-Easton, William A Figgett, Kirsten A Fairfax, Fabienne Mackay
The BAFF system plays a key role in the development of autoimmunity, especially in systemic lupus erythematosus (SLE). This often leads to the assumption that BAFF is mostly a B cell factor with a specific role in autoimmunity. Focus on BAFF and autoimmunity, driven by pharmaceutical successes with the recent approval of a novel targeted therapy Belimumab, has relegated other potential roles of BAFF to the background. Far from being SLE-specific, the BAFF system has a much broader relevance in infection, cancer and allergy...
June 2013: Cytokine & Growth Factor Reviews
Beata Powroźnik, Paulina Kubowicz, Elżbieta Pękala
Targeted therapy is a new therapeutic method consisting in the inhibition of specific molecular pathways. In modern therapy, the key role is played by monoclonal antibodies, included in the group of biological agents. The success of molecularly targeted therapy is to define the proper "molecular target", selecting the right drug active against a specific "target" and selecting a group of patients who benefit from treatment. Introduction of targeted therapy resulted in improved results of the treatment of many serious and chronic diseases...
2012: Postȩpy Higieny i Medycyny Doświadczalnej
Sukhvir Chand, Nisha Mehta, Malkeet Singh Bahia, Anshuman Dixit, Om Silakari
PKC-θ is a serine/threonine specific protein kinase and its activation depends upon the concentration of diacylglycerol (DAG) and phospholipids (phosphatidylserine). PKC-θ phosphorylates a variety of proteins that are known to be involved in the diverse cellular signaling pathways. It is predominantly expressed in the T-cells and localized in the center of immunological synapse upon T-cell receptor (TCR) and CD28 signaling. Activation of PKC-θ leads to the activation of various transcription factors in the nuclei of T-cells, e...
2012: Current Pharmaceutical Design
Mohan S Maddur, Pierre Miossec, Srini V Kaveri, Jagadeesh Bayry
Th17 cells that secrete the cytokines IL-17A and IL-17F and express lineage-specific transcription factor RORC (RORγt in mice) represent a distinct lineage of CD4(+) T cells. Transforming growth factor-β and inflammatory cytokines, such as IL-6, IL-21, IL-1β, and IL-23, play central roles in the generation of Th17 cells. Th17 cells are critical for the clearance of extracellular pathogens, including Candida and Klebsiella. However, under certain conditions, these cells and their effector molecules, such as IL-17, IL-21, IL-22, GM-CSF, and CCL20, are associated with the pathogenesis of several autoimmune and inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis, inflammatory bowel disease, and allergy and asthma...
July 2012: American Journal of Pathology
Saso Cemerski, Seung Y Chu, Gregory L Moore, Umesh S Muchhal, John R Desjarlais, David E Szymkowski
Mast cells and basophils play a central role in allergy, asthma, and anaphylaxis, as well as in non-allergic inflammatory, neurological and autoimmune diseases. Allergen-mediated cross-linking of IgE bound to FcεRI leads to cellular activation, and the low-affinity Fc receptor FcγRIIb is a key inhibitor of subsequent degranulation. FcγRIIb, when coengaged with FcεRI via allergen bound to IgE, stimulates ITIM domain-mediated inhibitory signaling that efficiently suppresses mast cell and basophil activation...
March 30, 2012: Immunology Letters
Lauren S Sherman, Jessian Munoz, Shyam A Patel, Meneka A Dave, Ilani Paige, Pranela Rameshwar
Although stem cell therapy is not a new field, the field was limited to transplantation of hematopoietic stem cells. Such transplantation has provided invaluable information for the emerging field with new stem cells. Mesenchymal stem cells (MSCs) are an attractive source for therapy; reduced ethical concern, ease in expansion, as off-the-shelf stem cells. MSCs exert immune suppressive properties, providing them with the potential for immune suppressive therapy such as autoimmunity, asthma, allergic rhinitis and graft versus host disease...
October 2011: Clinical and Translational Science
Gillian M Bell, Gary Reynolds, John D Isaacs
Biologic therapies have been licensed to treat rheumatic diseases for more than a decade. In parallel, they have gained acceptance in a variety of non-rheumatic diseases, where their impact has been no less revolutionary. In this Review, we examine the application of biologics in a number of non-rheumatic autoimmune and inflammatory disorders-psoriasis, inflammatory bowel disease, uveitis, asthma, diabetes, congestive cardiac failure and multiple sclerosis. In particular, we have sought information, or lessons, that could influence their application in rheumatic diseases...
August 2, 2011: Nature Reviews. Rheumatology
Sophie Chen
Inflammation is a natural response of living organisms to the presence of internal and external substances which are recognized by the host as being "non-self" or "foreign invader". It is also a cascade leading to the healing of damaged tissue. Uncontrolled inflammation often results in chronic diseases such as arthritis, autoimmune disorder, cancer, dementia, diabetic, neurodegeneration and vascular disease. The list keeps growing due to the increasing numbers of identified molecular markers that are associated with inflammatory genes or transcription factors...
March 1, 2011: Current Drug Targets
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