Costimulatory Pathways: Physiology and Potential Therapeutic Manipulation in Systemic Lupus Erythematosus

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 245928, 12 pages
http://dx.doi.org/10.1155/2013/245928

Review Article

Costimulatory Pathways: Physiology and Potential Therapeutic Manipulation in Systemic Lupus Erythematosus

Nien Yee Kow and Anselm Mak

Division of Rheumatology, Department of Medicine, University Medicine Cluster, Yong Loo Lin School of Medicine, National University of Singapore, Level 10, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228

Received 31 May 2013; Accepted 8 July 2013

Academic Editor: Guixiu Shi

Copyright © 2013 Nien Yee Kow and Anselm Mak. This is an open access article distributed under theCreative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

System lupus erythematosus (SLE) is an immune-complex-mediated autoimmune condition with protean immunological and clinical manifestation. While SLE has classically been advocated as a B-cell or T-cell disease, it is unlikely that a particular cell type is more pathologically predominant than the others. Indeed, SLE is characterized by an orchestrated interplay amongst different types of immunopathologically important cells participating in both innate and adaptive immunity including the dendritic cells, macrophages, neutrophils and lymphocytes, as well as traditional nonimmune cells such as endothelial, epithelial, and renal tubular cells. Amongst the antigen-presenting cells and lymphocytes, and between lymphocytes, the costimulatory pathways which involve mutual exchange of information and signalling play an essential role in initiating, perpetuating, and, eventually, attenuating the proinflammatory immune response. In this review, advances in the knowledge of established costimulatory pathways such as CD28/CTLA-4-CD80/86, ICOS-B7RP1, CD70-CD27, OX40-OX40L, and CD137-CD137L as well as their potential roles involved in the pathophysiology of SLE will be discussed. Attempts to target these costimulatory pathways therapeutically will pave more potential treatment avenues for patients with SLE. Preliminary laboratory and clinical evidence of the potential therapeutic value of manipulating these costimulatory pathways in SLE will also be discussed in this review.

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Mechano-insensitive Nociceptors are Sufficient to Induce Histamine-induced Itch

Mechano-insensitive Nociceptors are Sufficient to Induce Histamine-induced Itch

doi: 10.2340/00015555-1513

Abstract:

The nerve fibres underlying histamine-induced itch have not been fully elucidated. We blocked the lateral femoral cutaneous nerve and mapped the skin area unresponsive to mechanical stimulation, but still sensitive to electrically induced pain. Nerve block induced significantly larger anaesthetic areas to mechanical (100 mN pin-prick, 402 ± 61 cm2; brush, 393 ± 63 cm2) and heat pain stimuli (401 ± 53 cm2) compared with electrical stimulation (352 ± 62 cm2, p < 0.05), whereas the anaesthetic area tested with 260 mN (374 ± 57 cm2) did not differ significantly. Histamine was applied by iontophoresis (7.5 mC) at skin sites in which mechanical sensitivity was blocked, but electrical stimulation was still perceived 30 min after the nerve block (n = 9). In these areas iontophoresis of histamine provoked itching in 8/9 subjects with a mean maximum of 4.6 ± 1 (on an 11-point rating scale). Histamine-induced itch can thus be perceived at skin sites where input from mechano-sensitive polymodal nociceptors is blocked. In conclusion, input from mechano-insensitive nociceptors is sufficient to generate histamine-induced itch. 

Authors:

Marcus Schley, Roman Rukwied, James Blunk, Christian Menzer, Christoph Konrad, Martin Dusch, Martin Schmelz, Justus Benrath
Department of Anesthesiology, University of Heidelberg, DE-68167 Mannheim, Germany

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Expression of Hypothalamic–Pituitary–Adrenal Axis in Common Skin Diseases: Evidence of its Association with Stress-related Disease Activity

Expression of Hypothalamic–Pituitary–Adrenal Axis in Common Skin Diseases: Evidence of its Association with Stress-related Disease Activity

doi: 10.2340/00015555-1557

Abstract:

Hypothalamic–pituitary–adrenal (HPA) axis hormones and their receptors expressed in the skin are known to function locally, but how these hormones affect the maintenance of skin homeostasis or the pathogenesis of skin diseases is not fully understood. We comprehensively reviewed the distribution and function of the central and peripheral HPA axis in various stress-related skin diseases. Previous studies have shown altered expression of central and peripheral HPA axis hormones in chronic inflammatory skin diseases and skin tumours, and that hyper-active lesional HPA axis hormones may negatively feedback to the central HPA axis and interact with some cytokines and neuropeptides, leading to symptom deterio-ration. This provides an evidence-based understanding of the expression of the central and peripheral HPA axis in common skin diseases and its association with disease activity.

Authors:

Jung Eun Kim, Baik Kee Cho, Dae Ho Cho, Hyun Jeong Park
Department of Dermatology, College of Medicine, The Catholic University of Korea 620-56, Jeonnong-dong, Dongdaemun-ku, Seoul, Korea

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Allergy, Asthma and Immunology - Open and Full Access information for physicians interested in the topic

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Front. Immunol., 29 July 2013 | doi: 10.3389/fimmu.2013.00217

Expression of recombinant antibodies

André Frenzel*, Michael Hust and Thomas Schirrmann

• Abteilung Biotechnologie, Institut für Biochemie, Biotechnologie und Bioinformatik, Technische Universität Braunschweig, Braunschweig, Germany

Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

Keywords: recombinant antibody, procaryotes, yeast, fungi, insect cells, mammalian cell, transgenic organisms

Citation: Frenzel A, Hust M and Schirrmann T (2013) Expression of recombinant antibodies. Front. Immunol. 4:217. doi: 10.3389/fimmu.2013.00217

Received: 25 March 2013; Accepted: 15 July 2013;
Published online: 29 July 2013.

Edited by:

Danièle Altschuh, Centre National de la Recherche Scientifique, France

Reviewed by:

John D. Colgan, University of Iowa, USA
Andrea Gorlani, University of California Irvine, USA

Copyright: © 2013 Frenzel, Hust and Schirrmann. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: André Frenzel, Department of Biotechnology, Institute of Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Spielmannstr. 7, 38106 Braunschweig, Germany e-mail: andre.frenzel@tu-braunschweig.de

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The history of the idea of allergy

1. J. M. Igea^*

Article first published online: 29 JUL 2013

DOI: 10.1111/all.12174

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

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Allergy

Early View (Online Version of Record published before inclusion in an issue)

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1. Edited by: Thomas Bieber

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Keywords:

• allergy;
• anaphylaxis;
• history;
• hypersensitivity;
• terminology

Abstract

About 100 years ago, a young paediatrician understood that the function of the immune system should be rationalized not in terms of exemption of disease but in terms of change of reactivity. He coined a new word to represent such an idea: ‘allergy’: the first contact of the immune system with an antigen changes the reactivity of the individual; on the second and subsequent contacts, this change (or allergy) can induce a spectrum of responses from protective (literally, immune) to hypersensitivity ones. The idea was at first hardly understood by the scientific community because it undermined the essentially protective nature of the immune response as it was defined. Nevertheless, in the next years, the growing clinical evidence led to the acceptance of this new point of view, but not of the new word, at least not unconditionally. The original significance of the neologism ‘allergy’ became perverted and limited to describe hypersensitivity conditions. Perhaps because of the corruption of the term, today ‘allergy’ does not have a well-delimited significance among health professionals. Furthermore, the word has long ago escaped from physicians and gone to the streets, where it is popularly used also as synonymous with antipathy and rejection. This vulgarization of the term ‘allergy’ has significantly increased its imprecision.

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Immunology of atopic eczema: overcoming the Th1/Th2 paradigm

1. K. Eyerich^1,2,*, 
2. N. Novak³

Article first published online: 29 JUL 2013

DOI: 10.1111/all.12184

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

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Allergy

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1. Edited by: Stephan WeidingerArticle

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Keywords:

• dendritic cell;
• dermatitis;
• eczema;
• immunology;
• T cell

Abstract

Atopic eczema (AE) is a challenge for modern medicine, because it is prevalent, severely affects quality of life of patients and their families, and causes high socioeconomic costs. The pathogenesis of AE is complex. While initial studies suggested a Th2 deviation as primary reason for the disease, numerous studies addressed a genetically predetermined impaired epidermal barrier as leading cause in a subgroup of patients. Recently, immune changes beyond the initial Th2 concept were defined in AE, with a role for specialized dendritic cells as well as newly identified T helper cell subsets such as Th17 and Th22 cells. Furthermore, trigger factors are expanded beyond classical Th2 allergens such as pollen or house dust mites to microbial products as well as self-antigens. This review pieces together our current understanding of immune as well as barrier abnormalities into the pathogenesis mosaic of AE.

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Bilastine: A New Nonsedating Oral H1 Antihistamine for Treatment of Allergic Rhinoconjunctivitis and Urticaria

BioMed Research International
Volume 2013 (2013), Article ID 626837, 6 pages
http://dx.doi.org/10.1155/2013/626837

Review Article

Bilastine: A New Nonsedating Oral H1 Antihistamine for Treatment of Allergic Rhinoconjunctivitis and Urticaria

Ole D. Wolthers

Asthma and Allergy Clinic, Children’s Clinic Randers, Dytmærsken 9, 8900 Randers, Denmark

Received 5 April 2013; Accepted 26 June 2013

Academic Editor: Fulvio Braido

Copyright © 2013 Ole D. Wolthers. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the fasting state bilastine is quickly absorbed, but the absorption is slowed when it is taken with food or fruit juice. Therefore, it is recommended that bilastine is taken at least one hour before and no sooner than two hours after a meal. Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg once daily is as efficacious as other nonsedating antihistamines in allergic rhinoconjunctivitis and chronic urticaria in individuals from 12 and 18 years of age, respectively. Bilastine is efficacious in all nasal symptoms including obstruction and in eye symptoms. The observations indicate that non-sedating antihistamines, as opposed to what has been thought previously, may be helpful in patients with allergic rhinitis in whom nasal obstruction is a major concern. Current international guidelines need to be revised in the light of the recent evidence. Research into aspects of pharmacokinetics and efficacy and adverse effect profiles of bilastine in children under 12 years of age is needed as are dose-response assessments and studies planned rigorously with the aim of assessing quality of life effects.

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