Immunology In The Clinic

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In pursuit of excellence: an integrated care pathway for C1 inhibitor deficiency

1. A. L. Manson¹, 
2. A. Price⁴, 
3. J. Dempster¹, 
4. P. Clinton-Tarestad⁵, 
5. C. Greening², 
6. R. Enti⁶,
7. S. Hill³, 
8. S. Grigoriadou¹, 
9. M. S. Buckland¹,
10. H. J. Longhurst^1,*

Article first published online: 6 JUN 2013

DOI: 10.1111/cei.12083

© 2013 Crown Copyright. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland

Issue

Clinical & Experimental Immunology

Volume 173, Issue 1, pages 1–7, July 2013

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Keywords:

• angioedema;
• C1 inhibitor;
• commissioning;
• icatibant;
• integrated care pathway

Summary

There are estimated to be approximately 1500 people in the United Kingdom with C1 inhibitor (C1INH) deficiency. At BartsHealth National Health Service (NHS) Trust we manage 133 patients with this condition and we believe that this represents one of the largest cohorts in the United Kingdom. C1INH deficiency may be hereditary or acquired. It is characterized by unpredictable episodic swellings, which may affect any part of the body, but are potentially fatal if they involve the larynx and cause significant morbidity if they involve the viscera. The last few years have seen a revolution in the treatment options that are available for C1 inhibitor deficiency. However, this occurs at a time when there are increased spending restraints in the NHS and the commissioning structure is being overhauled. Integrated care pathways (ICP) are a tool for disseminating best practice, for facilitating clinical audit, enabling multi-disciplinary working and for reducing health-care costs. Here we present an ICP for managing C1 inhibitor deficiency.

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Reciprocal Interference of Experimental Dyslipidemia and Food Allergy in the Evolution of Both Diseases

ISRN Allergy
Volume 2013 (2013), Article ID 545184, 7 pages
http://dx.doi.org/10.1155/2013/545184

Research Article

Reciprocal Interference of Experimental Dyslipidemia and Food Allergy in the Evolution of Both Diseases

A. C. Gomes-Santos,^1,2 J. L. Gonçalves,^1,2 T. R. Fonseca,¹ A. R. Marques,²L. P. A. Dourado,³ D. C. Cara,³ and J. I. Alvarez-Leite^1,2

¹Department of Food, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
²Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Pampulha, 30161-970 Belo Horizonte, MG, Brazil
³Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

Received 23 April 2013; Accepted 19 May 2013

Academic Editors: A. Lorentz, C. Pereira, and B. Xu

Copyright © 2013 A. C. Gomes-Santos et al. 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

Background. Food allergies have been shown to reduce serum triacylglycerol, glucose, cholesterol, and free fatty acid levels in mice. In turn, dyslipidemias, especially dyslipidemias presenting with low levels of HDL cholesterol, are important risk factors for the development of atherosclerosis. However, the consequences of food allergies on dyslipidemia and atherosclerosis have not been fully investigated.Methods. Food allergy was induced using an egg white solution (EWS) in ovalbumin- (OVA-) sensitized C57BL/6 and low-density lipoprotein receptor knockout mice (LDLr^−/−) for 5 weeks and was confirmed by the high production of anti-OVA IgE and IgG1 antibodies in both mouse strains. Results. The allergic C57BL/6 mice exhibited EWS aversion that was associated with less visceral fat and high levels of anti-Ova IgE antibodies after 5 weeks of EWS intake compared to controls. However, LDLr^−/−allergic mice showed reduced anti-Ova IgE levels that were similar to the nonsensitized group. The LDLr^−/− allergic mice also demonstrated a reversal of food aversion and sustained visceral fat after 5 weeks of allergy. Although HDL cholesterol levels were reduced in both sensitized mouse strains, lipid deposition in thoracic and abdominal aorta as well as area and composition of atherosclerotic plaques as unaffected by chronic ingestion of EWS. Conclusion. LDLr^−/− mice develop an attenuated food allergy, as they showed a reversal of food aversion and lower IgE production after 5 weeks of induced allergy. The development of atherosclerosis, in turn, was not accelerated in the allergic LDLr^−/− group despite the more atherogenic lipid profile.

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Multiantibody Strategies for HIV

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 632893, 11 pages
http://dx.doi.org/10.1155/2013/632893

Review Article

Multiantibody Strategies for HIV

Andrew Hiatt, Larry Zeitlin, and Kevin J. Whaley

Mapp Biopharmaceutical Inc., 6160 Lusk Boulevard, C104, San Diego, CA 92121, USA

Received 15 March 2013; Revised 13 May 2013; Accepted 14 May 2013

Academic Editor: Roberto Burioni

Copyright © 2013 Andrew Hiatt et al. 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

Vaccination strategies depend entirely on the appropriate responsiveness of our immune system against particular antigens. For this active immunization to be truly effective, neutralizing antibodies (nAbs) need to efficiently counter the infectivity or propagation of the pathogen. Some viruses, including HIV, are able to take advantage of this immune response in order to evade nAbs. This review focuses on viral immune evasion strategies that result directly from a robust immune response to infection or vaccination. A rationale for multi-Ab therapy to circumvent this phenomenon is discussed. Progress in the formulation, production, and regulatory approval of monoclonal antibodies (mAbs) is presented.

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Review Article

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The consequences of not having eosinophils

1. G. J. Gleich^1,*, 
2. A. D. Klion², 
3. J. J. Lee³, 
4. P. F. Weller⁴

Article first published online: 6 JUN 2013

DOI: 10.1111/all.12169

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

Issue

Allergy

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Keywords:

• anti-interleukin 5;
• deficiency;
• eosinophil;
• thymoma

Abstract

Several lines of evidence suggest that deficiency of eosinophils is not associated with any characteristic abnormality. Patients lacking eosinophils, in the setting of immunodeficiency or as a consequence of IgG-mediated eosinophil precursor destruction, do not display any distinguishing abnormalities related to eosinophil reduction. The observation that eosinophil-deficient mice do not display any distinctive syndrome or failure of their health is evidence that, under ordinary laboratory conditions, the eosinophil does not play a critical role in the well-being of mammals. Observations that monoclonal antibodies to interleukin-5 (IL-5) are well tolerated appear unsurprising in light of these findings. For example, patients with the hypereosinophilic syndrome have received mepolizumab, an anti-IL-5 monoclonal antibody, for as long as 6 years and have not developed any characteristic set of adverse events. Safety data for reslizumab, another anti-IL-5 monoclonal antibody, and benralizumab, a monoclonal antibody to the IL-5 receptor α-chain, are comparatively limited, especially for benralizumab, although reports of administration of these antibodies to humans suggest that they are well tolerated. Thus, data to the present suggest that reduction of eosinophils appears to have no characteristic ill effects on normal health, and monoclonal antibodies that deplete eosinophils have the potential to be widely employed in the treatment of eosinophil-associated diseases.

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 Journal of Asthma and Allergy

Extrafine inhaled corticosteroid therapy in the control of asthma

Review

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Authors: Ivancsó I, Böcskei R, Müller V, Tamási L

Published Date June 2013 Volume 2013:6 Pages 69 - 80

DOI: http://dx.doi.org/10.2147/JAA.S25415

Received:	07 December 2012
Accepted:	30 April 2013
Published:	06 June 2013

István Ivancsó, Renáta Böcskei, Veronika Müller, Lilla Tamási

Department of Pulmonology, Semmelweis University, Budapest, Hungary

Abstract: Small airways disease plays an important role in the pathogenesis of asthma, but assessment of small airways impairment is not easy in everyday clinical practice. The small airways can be examined by several invasive and noninvasive methods, most of which can at present be used only in the experimental setting. Inhalers providing extrafine inhaled corticosteroid particle sizes may achieve sufficient deposition in the peripheral airways. Many studies have reported the beneficial effects of extrafine inhaled corticosteroids on inflammation, ie, on dysfunction in both the central and distal airways in asthmatics, and there are some data on asthma phenotypes in which the small airways seem to be affected more than in other phenotypes, including nocturnal asthma, severe steroid-dependent or difficult-to-treat asthma, asthma complicated by smoking, elderly asthmatic patients and/or patients with fixed airflow obstruction, and asthmatic children. The relevant randomized controlled clinical trials indicate that the efficacy of extrafine and nonextrafine inhaled corticosteroid formulations is similar in terms of primary endpoints, but there are certain clinically important endpoints for which the extrafine formulations show additional benefits.

Keywords: small airways, inflammation, dysfunction, noninvasive evaluation methods, peripheral deposition



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 International Journal of Chronic Obstructive Pulmonary Disease

Day-to-day measurement of patient-reported outcomes in exacerbations of chronic obstructive pulmonary disease

Original Research

(64) Total Article Views

Authors: Kocks JWH, van den Berg JWK, Kerstjens HAM, Uil SM, Vonk JM, de Jong YP, Tsiligianni IG, van der Molen T

Published Date June 2013 Volume 2013:8 Pages 273 - 286

DOI: http://dx.doi.org/10.2147/COPD.S43992

Received:	13 February 2013
Accepted:	11 March 2013
Published:	06 June 2013

Jan Willem H Kocks,^1,2 Jan Willem K van den Berg,³ Huib AM Kerstjens,^2,4 Steven M Uil,³ Judith M Vonk,^2,5 Ynze P de Jong,³ Ioanna G Tsiligianni,^1,2 Thys van der Molen^1,2
1Department of General Practice, ²Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, ³Department of Pulmonary Diseases, Isala Klinieken, Zwolle, ⁴Department of Pulmonary Diseases and Tuberculosis,⁵Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are a major burden to patients and to society. Little is known about the possible role of day-to-day patient-reported outcomes during an exacerbation. This study aims to describe the day-to-day course of patient-reported health status during exacerbations of COPD and to assess its value in predicting clinical outcomes.
Methods: Data from two randomized controlled COPD exacerbation trials (n = 210 and n = 45 patients) were used to describe both the feasibility of daily collection of and the day-to-day course of patient-reported outcomes during outpatient treatment or admission to hospital. In addition to clinical parameters, the BORG dyspnea score, the Clinical COPD Questionnaire (CCQ), and the St George's Respiratory Questionnaire were used in Cox regression models to predict treatment failure, time to next exacerbation, and mortality in the hospital study.
Results: All patient-reported outcomes showed a distinct pattern of improvement. In the multivariate models, absence of improvement in CCQ symptom score and impaired lung function were independent predictors of treatment failure. Health status and gender predicted time to next exacerbation. Five-year mortality was predicted by age, forced expiratory flow in one second % predicted, smoking status, and CCQ score. In outpatient management of exacerbations, health status was found to be less impaired than in hospitalized patients, while the rate and pattern of recovery was remarkably similar.
Conclusion: Daily health status measurements were found to predict treatment failure, which could help decision-making for patients hospitalized due to an exacerbation of COPD.

Keywords: health status, Clinical COPD Questionnaire, hospital, admission, prediction



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Review

Novel therapeutic agents in clinical development for systemic lupus erythematosus

Natasha Jordan, Pamela MK Lutalo and David P D’Cruz^*

• *Corresponding author: David P D’Cruz david.dcruz@kcl.ac.uk

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BMC Medicine 2013, 11:120 doi:10.1186/1741-7015-11-120

Published: 3 May 2013

Abstract

Conventional immunosuppressive therapies have radically transformed patient survival in systemic lupus erythematosus (SLE), but their use is associated with considerable toxicity and a substantial proportion of patients remain refractory to treatment. A more comprehensive understanding of the complexity of SLE immunopathogenesis has evolved over the past decade and has led to the testing of several biologic agents in clinical trials. There is a clear need for new therapeutic agents that overcome these issues, and biologic agents offer exciting prospects as future SLE therapies.

An array of promising new therapies are currently emerging or are under development including B-cell depletion therapies, agents targeting B-cell survival factors, blockade of T-cell co-stimulation and anti-cytokine therapies, such as monoclonal antibodies against interleukin-6 and interferon-α.

Keywords: 

Lupus nephritis; B-cell depletion; BLys; T-cell co-stimulation; Interferon-α, SLE

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Research article

A qualitative study of the coverage of influenza vaccination on Dutch news sites and social media websites

Birthe A Lehmann, Robert AC Ruiter and Gerjo Kok

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BMC Public Health 2013, 13:547 doi:10.1186/1471-2458-13-547

Published: 5 June 2013

Abstract (provisional)

Background

Information about influenza and the effectiveness of vaccination against influenza is largely available on the Internet, and may influence individual decision making about participation in future influenza vaccination rounds. E-health information has often been found to be inaccurate, or even to contradict Health Authority recommendations, especially when it concerns controversial topics.

Methods

By means of an online media monitoring programme, Dutch news sites and social media websites were scanned for the Dutch counterparts of the terms influenza, vaccination, vaccine and epidemic during February, March and April 2012. Data were processed with QSR NVivo 8.0 and analysed using a general inductive approach.

Results

Three overarching themes were found in both media sources: (1) the (upcoming) influenza epidemic, (2) general information regarding the virus, its prevention and treatment, and (3) uncertainty and mistrust regarding influenza vaccination. Social media tended to report earlier on developments such as the occurrence of an influenza epidemic. The greatest difference was that in social media, influenza was not considered to be a serious disease, and more opposition to the flu shot was expressed in social media, as compared to news media.

Conclusions

News media and social media discussed the same topics regarding influenza, but differed in message tone. Whereas news media reports tended to be more objective and non-judgmental, social media more critically evaluated the harmfulness of influenza and the necessity of the flu shot. Media may influence decision making and behaviours of Internet users and may thereby influence the success of vaccination campaigns and recommendations made by health authorities. Social media may be more of a problem in this sense, since it is neither controlled nor censored. Future research should investigate the actual impact of Internet media on the influenza decision making process of its users.

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