Regulation of intestinal health and disease by innate lymphoid cells

Int. Immunol. (2014) 26 (9): 501-507. doi: 10.1093/intimm/dxu052 First published online: May 12, 2014

Gregory F. Sonnenberg

Abstract

Innate lymphoid cells (ILCs) are a recently appreciated immune cell population that is constitutively found in the healthy mammalian gastrointestinal (GI) tract and associated lymphoid tissues. Translational studies have revealed that alterations in ILC populations are associated with GI disease in patients, such as inflammatory bowel disease, HIV infection and colon cancer, suggesting a potential role for ILCs in either maintaining intestinal health or promoting intestinal disease. Mouse models identified that ILCs have context-dependent protective and pathologic functions either during the steady state, or following infection, inflammation or tissue damage. This review will discuss the associations of altered intestinal ILCs with human GI diseases, and the functional consequences of targeting ILCs in mouse models. Collectively, our current understanding of ILCs suggests that the development of novel therapeutic strategies to modulate ILC responses will be of significant clinical value to prevent or treat human GI diseases.

© The Japanese Society for Immunology. 2014. All rights reserved.

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Japanese Guideline for Allergic Rhinitis 2014

REVIEW ARTICLE

doi:10.2332/allergolint.14-RAI-0768

Kimihiro Okubo, Yuichi Kurono, Shigeharu Fujieda, Satoshi Ogino, Eiichi Uchio, Hiroshi Odajima, Hiroshi Takenaka and Japanese Society of Allergology 

ABSTRACT

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 7th edition was published in 2013, and is widely used today.

To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2013. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.

KEY WORDS:

allergen immunotherapy, mechanism, pharmacotherapy, pollinosis, surgery

Received: 28 April 2014.

Allergology International 2014; 63: 357-375 (Full text)

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Therapeutic uses of anti-interleukin-6 receptor antibody

1. Int. Immunol. (2014) doi: 10.1093/intimm/dxu081 
2. First published online: August 20, 2014
3. Sujin Kang¹,²,
4. Toshio Tanaka¹,² and
5. Tadamitsu Kishimoto³

1. ¹Department of Clinical Application of Biologics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita City, 
2. Osaka 565-0871, Japan
3. ²Department of Immunopathology, World Premier International Immunology Frontier Research Center, Osaka University, 
4. 3-1 Yamada-oka, Suita City, Osaka 565-0871, Japan
5. ³Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, 
6. 3-1 Yamada-oka, Suita City, Osaka 565-0871, Japan

1. Corresponding author: Tadamitsu Kishimoto Contact email: kishimoto@ifrec.osaka-u.ac.jp Laboratory of Immune Regulation, 
2. World Premier International Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita City, Osaka 565-0871, Japan

• Received July 13, 2014.

Abstract

Cytokine-targeted therapy has generated a paradigm shift in the treatment of several immune-mediated diseases. Interleukin 6 (IL-6), which was initially identified as a B cell stimulatory factor 2, is a prototypical cytokine with wide-ranging biological effects on immune cells such as B and T cells, hepatocytes, hematopoietic cells, vascular endothelial cells, and many others. IL-6 is thus crucially involved in the regulation of immune response, hematopoiesis, and inflammation. When infections and tissue injuries occur, IL-6 is promptly synthesized and performs a protective role in host defense against such stresses and traumas. However, excessive production of IL-6 during this emergent process induces potentially fatal complications, including systemic inflammatory response syndrome (SIRS), while dysregulated, persistently high expression of IL-6 causes the onset or development of various chronic immune-mediated disorders. For these reasons, IL-6 blockade was expected to become a novel therapeutic strategy for various diseases characterized by IL-6 overproduction. Indeed, worldwide clinical trials of tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, have successfully proved its outstanding efficacy against rheumatoid arthritis, juvenile idiopathic arthritis, and Castleman disease, leading to the approval of tocilizumab for the treatment of these diseases. Moreover, various reports regarding off-label use with tocilizumab strongly suggest that it will be widely applicable for acute severe complications such as SIRS and cytokine release syndrome and other refractory chronic immune-mediated diseases.

Key words

• autoimmune diseases
 
• chronic inflammatory diseases
 
• IL-6
 
• tocilizumab

• 
  
• 
  

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Anaphylaxis and cardiovascular diseases: a dangerous liaison

Current Opinion in Allergy & Clinical Immunology:

August 2014 - Volume 14 - Issue 4 - p 309-315

Triggiani, Massimo^a; Montagni, Marcello^b; Parente, Roberta^a; Ridolo, Erminia^b

Free Access

Article Outline

Author Information

^aDivision of Allergy and Clinical Immunology, University of Salerno, Salerno

^bDepartment of Clinical and Experimental Medicine, University of Parma, Italy

Correspondence to Massimo Triggiani, MD, Division of Allergy and Clinical Immunology, Department of Medicine, University of Salerno, Via Allende, 84081 Baronissi (Salerno), Italy. Tel: +39 081 965056; e-mail: mtriggiani@unisa.it

Abstract

Purpose of review

Anaphylaxis is a life-threatening event in which the cardiovascular system is responsible for the majority of clinical symptoms and for potentially fatal outcome. This review summarizes the most recent clinical and experimental data on cardiovascular involvement during anaphylaxis.

Recent findings

Great efforts have been made in the last few years to understand the pathophysiology of anaphylactic reaction and to provide better identification of risk factors for the development of this reaction. Coronary blood flow can be impaired during anaphylaxis, which may significantly contribute to an unfavourable outcome. Also, preexisting coronary artery disease is a negative prognostic factor for anaphylaxis. In addition, acute ischemic events, including angina and myocardial infarction, are currently considered as part of the clinical picture of anaphylaxis. Moreover, cardiac emergency can be the presenting clinical picture of mast cell-related disorders.

Summary

Both cardiovascular and allergic diseases are frequent among populations. A better understanding of the mechanisms leading to cardiac mast cell activation and the effects of mast cell mediators on cardiovascular system can help improve the prevention and treatment of anaphylaxis.

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Dietary exposures and allergy prevention in high-risk infants: a joint position statement of the Canadian Society of Allergy and Clinical Immunology and the Canadian Paediatric Society

Review

Edmond S Chan, Carl Cummings, Adelle Atkinson, Zave Chad, Marie-Josée Francoeur, Linda Kirste, Douglas Mack, Marie-Noël Primeau, Timothy K Vander Leek and Wade TA Watson

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Allergy, Asthma & Clinical Immunology 2014, 10:45  doi:10.1186/1710-1492-10-45

Published: 2 September 2014

Abstract (provisional)

Allergic conditions in children are a prevalent health concern in Canada. The burden of disease and the societal costs of proper diagnosis and management are considerable, making the primary prevention of allergic conditions a desirable health care objective. This position statement reviews current evidence on dietary exposures and allergy prevention in infants at high risk of developing allergic conditions. It revisits previous dietary recommendations for pregnancy, breastfeeding and formula-feeding, and provides an approach for introducing solid foods to high-risk infants. While there is no evidence that delaying the introduction of any specific food beyond six months of age helps to prevent allergy, the protective effect of early introduction of potentially allergenic foods (at four to six months) remains under investigation. Recent research appears to suggest that regularly ingesting a new, potentially allergenic food may be as important as when that food is first introduced. This article has already been published (Paediatr Child Health. 2013 Dec;18(10):545-54), and is being re-published with permission from the original publisher, the Canadian Paediatric Society.

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The value of family history in diagnosing primary immunodeficiency disorders

Case Rep Pediatr. 2014;2014:516256. doi: 10.1155/2014/516256. Epub 2014 Aug 5.

Hendaus MA1, Alhammadi A2, Adeli MM3, Al-Yafei F4.

Author information

Abstract

Eliciting proper family medical history is critical in decreasing morbidity and mortality in patients with primary immunodeficiency disorders (PIDs). Communities with a common practice of consanguinity have a high rate of PIDs. We are presenting 2 cases where digging deeply into the family medical history resulted in the diagnosis of Omenn syndrome, a possibly fatal entity if not managed in a reasonable period.

PMID:

 

25161792

 

[PubMed] 

PMCID:

 

PMC4137698

 

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Skin prick/puncture testing in North America: a call for standards and consistency

Research

Shahnaz Fatteh, Donna J Rekkerth and James A Hadley

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Allergy, Asthma & Clinical Immunology 2014, 10:44  doi:10.1186/1710-1492-10-44

Published: 2 September 2014

Abstract (provisional)

Background

Skin prick/puncture testing (SPT) is widely accepted as a safe, dependable, convenient, and cost-effective procedure to detect allergen-specific IgE sensitivity. It is, however, prone to influence by a variety of factors that may significantly alter test outcomes, affect the accuracy of diagnosis, and the effectiveness of subsequent immunotherapy regimens. Proficiency in SPT administration is a key variable that can be routinely measured and documented to improve the predictive value of allergy skin testing.

Methods

Literature surveys were conducted to determine the adherence to repeated calls for development and implementation of proficiency testing standards in the 1990's, the mid-2000's and the 2008 allergy diagnostics practice parameters.

Results

Authors publishing clinical research in peer-reviewed journals and conducting workshops at annual scientific meetings have recommended proficiency testing based primarily on its potential to reduce variability, minimize confounding test results, and promote more effective immunotherapeutic treatments. Very few publications of clinical studies, however, appear to report proficiency testing data for SPT performance. Allergen immunotherapy recommendations are updated periodically by the Joint Task Force on Practice Parameters representing the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the Joint Council of Allergy, Asthma and Immunology (JCAAI).

Conclusions

Despite consensus that all staff who perform SPT should meet basic quality assurance standards that demonstrate their SPT proficiency, the gap between recommendations and daily practice persists. By embracing standards, the accuracy of SPT and allergy diagnosis can be optimized, ultimately benefiting patients with allergic disease.

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Serum angiopoietin is associated with lung function in patients with asthma: a retrospective cohort study

Research article

Kuk-Young Moon, PuReun-HaNeul Lee, Sung-Woo Park, Choon-Sik Park and An-Soo Jang

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BMC Pulmonary Medicine 2014, 14:143  doi:10.1186/1471-2466-14-143

Published: 2 September 2014

Abstract (provisional)

Background

Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis that establishes vascular integrity, and angiopoietin-2 (Ang-2) acts as its natural inhibitor. We considered that angiopoietin might be important in bronchial asthma.

Methods

In total, 35 patients with asthma and 20 healthy subjects were studied.

Results

The serum Ang-1 levels were significantly elevated in patients with asthma compared to control subjects (293.9 +/- 13.8 pg/mL vs. 248.3 +/- 16.2 pg/mL, respectively, p = 0.04). The serum Ang-2 levels were not different between the two groups. The areas under the curve (AUC) for serum angiopoietins revealed that the serum level of Ang-1 (0.68) was more sensitive and specific than the serum Ang-2 level (0.55) for differentiating between patients with asthma and control subjects. The serum Ang-1/Ang-2 ratio was correlated with the FEV1/FVC ratio (r = -0.312, p = 0.02), while serum Ang-2 was correlated with body mass index.

Conclusions

Our results indicate that the serum Ang-1 levels were higher in asthma patients compared with healthy subjects. As the Ang-1/Ang-2 ratio was related to lung function, the data suggest that serum angiopoietin is associated with lung function in patients with asthma.

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Specific IgE to fish extracts does not predict allergy to specific species within an adult fish allergic population

Research

Karlijn JG Schulkes, Rob JB Klemans, Lidy Knigge, Marjolein de Bruin-Weller, Carla AFM Bruijnzeel-Koomen, Åsa Marknell deWitt, Jonas Lidholm and André C Knulst

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Clinical and Translational Allergy 2014, 4:27  doi:10.1186/2045-7022-4-27

Published: 1 September 2014

Abstract (provisional)

Background

Fish is an important cause of food allergy. Studies on fish allergy are scarce and in most cases limited to serological evaluation. Our objective was to study patterns of self-reported allergy and tolerance to different commonly consumed fish species and its correlation to IgE sensitization to the same species.

Methods

Thirty-eight adult fish allergic patients completed a questionnaire regarding atopy, age of onset and symptoms to 13 commonly consumed fish species in the Netherlands (pangasius, cod, herring, eel, hake, pollock, mackerel, tilapia, salmon, sardine, tuna, plaice and swordfish). Specific IgE to these fish extracts were analyzed by ImmunoCAP.

Results

Median age of onset of fish allergy was 8.5 years. Severe reactions were reported by the majority of patients (n = 20 (53%) respiratory and of these 20 patients, 6 also had cardiovascular symptoms). After diagnosis, 66% of the patients had eliminated all fish from their diet. Allergy to all species ever tried was reported by 59%. In relation to species ever tried, cod (84%) and herring (79%) were the most frequently reported culprit species while hake (57%) and swordfish (55%) were the least frequent. A positive sIgE (value >= 0.35 kUA/L) to the culprit species ranged between 50% (swordfish) and 100% (hake). In tolerant patients, a negative sIgE (value - 0.35 kUA/L) ranged from 0% (hake, pollock and swordfish) to 75% (sardine). For cod, the agreement between sIgE test results and reported allergy or tolerance was 82% and 25%, respectively. Sensitization to cod parvalbumin (Gad c 1) was present in 77% of all patients.

Conclusion

Serological cross-reactivity between fish species is frequent, but in a significant proportion of patients, clinical relevance appears to be limited to only certain species. A well-taken history or food challenge is required for discrimination between allergy to the different fish species.

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