Depletion of major pathogenic cells in asthma by targeting CRTh2

Tao Huang,1 Meredith Hazen,2 Yonglei Shang,2 Meijuan Zhou,1 Xiumin Wu,1 Donghong Yan,1 Zhonghua Lin,1 Margaret Solon,3 Elizabeth Luis,4 Hai Ngu,3 Yongchang Shi,5 Arna Katewa,1 David F. Choy,6 Nandhini Ramamoorthi,6 Erick R. Castellanos,4 Mercedesz Balazs,1 Min Xu,1 Wyne P. Lee,1 Marissa L. Matsumoto,4 Jian Payandeh,7 Joseph R. Arron,6Jo-Anne Hongo,2 Jianyong Wang,5 Isidro Hötzel,2 Cary D. Austin,3 and Karin Reif1

Research Article Immunology Therapeutics

Abstract

Eosinophilic inflammation and Th2 cytokine production are central to the pathogenesis of asthma. Agents that target either eosinophils or single Th2 cytokines have shown benefits in subsets of biomarker-positive patients. More broadly effective treatment or disease-modifying effects may be achieved by eliminating more than one inflammatory stimulator. Here we present a strategy to concomitantly deplete Th2 T cells, eosinophils, basophils, and type-2 innate lymphoid cells (ILC2s) by generating monoclonal antibodies with enhanced effector function (19A2) that target CRTh2 present on all 4 cell types.

Predictive Factors for Medical Consultation for Sore Throat in Adults with Recurrent Pharyngotonsillitis

International Journal of Otolaryngology
Volume 2016 (2016), Article ID 6095689, 5 pages
http://dx.doi.org/10.1155/2016/6095689

Research Article

T. Koskenkorva,1,2,3 P. Koivunen,1,2,3 and O.-P. Alho1,2,3

1Department of Otorhinolaryngology and Head and Neck Surgery, Oulu University Hospital, Finland
2PEDEGO Research Unit, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland
3Medical Research Center Oulu, Finland

Abstract

Objects. To seek patient- and episode-related factors that associate with medical consultation for acute sore throat because these factors may affect the patient being referred to specialist care and tonsillectomy for recurrent pharyngotonsillitis. Methods. In a secondary analysis of two prior randomised controlled trials, sore throat episodes and medical visits were explored among 156 adult patients referred for tonsillectomy because of recurrent pharyngotonsillitis. Results. The 156 patients (104 females, mean age of 26 years) suffered from 208 acute pharyngotonsillitis episodes during 5-6 months of follow-up. Forty (25%) patients visited a physician, and female gender (adjusted hazard ratio, HR, 3.3; 95% confidence interval 1.4–8.0) and finding of chronically infected tonsils (HR 2.7; 1.2–6.1) were associated with medical consultation.

Therapeutic anti-CD3 monoclonal antibodies: from bench to bedside

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Immunotherapy

Posted online on May 10, 2016.

(doi:10.2217/imt-2016-0049)

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 Unported License

Chantal Kuhn¹ & Howard L Weiner*^,1

*Author for correspondence: hweiner@rics.bwh.harvard.edu

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ChooseABSTRACTBackgroundTregs in autoimmune disea...Anti-CD3 mAb in animal mo...New mouse models for test...Oral administration of an...How does oral anti-CD3 mA...Nasal administration of a...Clinical development of a...Clinical trials with intr...Clinical trials with oral...Combination therapies wit...Combination therapies wit...Conclusion & future persp...References

ABSTRACT	ChooseTop of pageABSTRACT <<BackgroundTregs in autoimmune disea...Anti-CD3 mAb in animal mo...New mouse models for test...Oral administration of an...How does oral anti-CD3 mA...Nasal administration of a...Clinical development of a...Clinical trials with intr...Clinical trials with oral...Combination therapies wit...Combination therapies wit...Conclusion & future persp...References

The induction of tolerance is a major goal of immunotherapy. Investigations over the last 20 years have shown that anti-CD3 monoclonal antibodies (mAbs) effectively treat autoimmune disease in animal models and have also shown promise in clinical trials. Tolerance induction by anti-CD3 mAbs is related to the induction of Tregs that control pathogenic autoimmune responses. Here, we review preclinical and clinical studies in which intravenous or mucosal administration of anti-CD3 mAbs has been employed and provide an outlook on future developments to enhance the efficacy of this promising therapeutic approach.

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Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study

Respiratory Research201617:43P. E. Silkoff, M. Laviolette, D. Singh, J. M. FitzGerald, S. Kelsen, V. Backer, C. Porsbjerg, P. O. Girodet, P. Berger, J. N. Kline, S. Khatri, P. Chanez, V. S. Susulic, E. S. Barnathan, F. Baribaud, M. J. Loza and for the ADEPT Investigators

Abstract

Background

Asthma is a biologically heterogeneous disease and development of novel therapeutics requires understanding of pathophysiologic phenotypes. There is uncertainty regarding the stability of clinical characteristics and biomarkers in asthma over time. This report presents the longitudinal stability over 12 months of clinical characteristics and clinically accessible biomarkers from ADEPT.

Can we identify patients at risk of life-threatening allergic reactions to food?

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.

1. Paul J. Turner¹, 
2. Joseph L. Baumert²,
3. Kirsten Beyer³, 
4. Robert Boyle¹, 
5. Chun-Han Chan⁴, 
6. Andrew Clark⁵, 
7. René W.R. Crevel⁶,
8. Audrey DunnGalvin⁷, 
9. Montserrat Fernández Rivas⁸, 
10. Hazel M. Gowland⁹, 
11. Linus Grabenhenrich¹⁰, 
12. Sarah Hardy⁴, 
13. Geert F Houben¹¹, 
14. Jonathan O'B Hourihane¹²,
15. Antonella Muraro¹³, 
16. Lars K. Poulsen¹⁴,
17. Katarzyna Pyrz⁷, 
18. Benjamin C. Remington¹¹,
19. Sabine Schnadt¹⁵, 
20. Ronald van Ree¹⁶,
21. Carina Venter¹⁷, 
22. Margitta Worm¹⁸, 
23. Clare E.N. Mills¹⁹, 
24. Graham Roberts^20,21,22,*and
25. Barbara K. Ballmer
Weber²³

DOI: 10.1111/all.12924

• Abstract
• Cited By

Abstract

Anaphylaxis has been defined as a “severe, life-threatening generalized or systemic hypersensitivity reaction”. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur, and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management.

Mechanisms of Anaphylaxis Beyond IgE

J Investig Allergol Clin Immunol 2016; Vol. 26(2): 73-82 doi: 10.18176/jiaci.0046 Muñoz-Cano R1,2,4, Picado C1,2,3, Valero A1,2,3, Bartra J1,2,4 1Unitat d'Al·lergia, Servei de Pneumologia, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain 2Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain 3Centro de Investigaciones Biomedicas en Red de Enfermedades Respiratorias (CIBERES), Spain 4Red de Investigación de Reacciones Adversas a Alérgenos y Fármacos (RIRAAF), Instituto de Salud Carlos III (ISCIII), Spain    Abstract Anaphylaxis is an acute, life-threatening, multisystem syndrome resulting from the sudden release of mediators derived from mast cells and basophils. Food allergens are the main triggers of anaphylaxis, accounting for 33%-56% of all cases and up to 81% of cases of anaphylaxis in children. Human anaphylaxis is generally thought to be mediated by IgE, with mast cells and basophils as key players, although alternative mechanisms have been proposed.

Measurement of Lung Function and Bronchial Inflammation in Children Is Underused by Spanish Allergists

J Investig Allergol Clin Immunol 2016; Vol. 26(2): 126-128doi: 10.18176/jiaci.0028 Sánchez-García S1, Olaguibel JM2, Quirce S3, Ibáñez MD1 on behalf of the Pediatric Allergy Committee, Spanish Society of Allergy and Clinical Immunology

1Allergy Section, Hospital Infantil Universitario Niño Jesús, Madrid, Spain 2Allergy Department, Complejo Hospitalario Universitario de Navarra, Pamplona, Spain 3Allergy Department, Hospital Universitario La Paz, Madrid, Spain

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Prevention of food allergy

April 2016Volume 137, Issue 4, Pages 998–1010

George du Toit, MD

,

 Teresa Tsakok, MRCP

,

 Simon Lack, BA

,

 Gideon Lack, MD

Open Access

DOI: http://dx.doi.org/10.1016/j.jaci.2016.02.005

                           

 

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Abstract

The past few decades have witnessed an increase in the prevalence of IgE-mediated food allergy (FA). For prevention strategies to be effective, we need to understand the causative factors underpinning this rise. Genetic factors are clearly important in the development of FA, but given the dramatic increase in prevalence over a short period of human evolution, it is unlikely that FA arises through germline genetic changes alone. A plausible hypothesis is that 1 or more environmental exposures, or lack thereof, induce epigenetic changes that result in interruption of the default immunologic state of tolerance.

Antibiotic-Induced Changes in the Intestinal Microbiota and Disease

Publication stage: In Press Corrected Proof

DOI: http://dx.doi.org/10.1016/j.molmed.2016.04.003

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The gut microbiota is a key player in many physiological and pathological processes occurring in humans. Recent investigations suggest that the efficacy of some clinical approaches depends on the action of commensal bacteria. Antibiotics are invaluable weapons to fight infectious diseases. However, by altering the composition and functions of the microbiota, they can also produce long-lasting deleterious effects for the host. The emergence of multidrug-resistant pathogens raises concerns about the common, and at times inappropriate, use of antimicrobial agents.

Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling

NATURE COMMUNICATIONS | ARTICLE OPEN

Shin-ichiro Honda,

Kazuki Sato,

Naoya Totsuka,

Satoshi Fujiyama,

Manabu Fujimoto,

Kensuke Miyake,

Chigusa Nakahashi-Oda,

Satoko Tahara-Hanaoka,

Kazuko Shibuya

& Akira Shibuya

• Affiliations
• Contributions
• Corresponding author

Nature Communications

 

7,

 

Article number:

 

11498

 

doi:10.1038/ncomms11498

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Abstract

• Abstract• 
• Introduction• 
• Results• 
• Discussion• 
• Methods• 
• Additional information• 
• References•
• Acknowledgements• 
• Author information• 
• Supplementary information

Marginal zone (MZ) B cells produce a first wave of antibodies for protection from blood-borne pathogens. However, the role of MZ B cells in inflammatory responses has not been elucidated. Here we show that MZ B cells produce pro-inflammatory cytokines, such as interleukin-6 (IL-6), and exacerbate systemic inflammatory responses to lipopolysaccharide (LPS).

Drug safety: withdrawn medications are only part of the picture

OPEN ACCESS

BMC Medicine201614:28

DOI: 10.1186/s12916-016-0579-5

Abstract

In a research article published in BMC Medicine, Onakpoya and colleagues provide a historical review of withdrawals of medications for safety reasons. However, withdrawn medications are only one part of the picture about how regulatory agencies manage drug risks. Moreover, medications introduced before the increased pre-marketing regulations and post-marketing monitoring systems instituted after the thalidomide tragedy have little relevance when considering the present drug safety picture because the circumstances under which they were introduced were completely different.