2013 APCAACI conference

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Allergy in the Emerging World:
2013 Asia Pacific Congress of Allergy, Asthma and Clinical Immunology
Allergy, Infection and Immunity in a Changing World.

Nov 14-17. Registration open until Oct 25. Unless something unforeseen comes along DH should be in attendance. It's one of the first cross-straits efforts on immunology with some representatives from Switzerland, Australia, USA and Germany. Most is in English, one or two in Mandarin.

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Please take a moment to review schedule of sessions, plenaries and speakers. We are open to requests on which are in LTFA research interest and anaphylaxis management. Many countries spanning Europe, Asia and North America in attendance. Amongst the 'local' speakers is Tse Wen Chang whose anti-IgE work in Tanox (in Texas) led to Xolair. He continues his anti-IgE work in Taiwan at Academia Sinica.

On DH's schedule is to look at therapies being discussed, and to ask some of the immunology researchers and allergists from China (mainland, Taiwan and/or HK) about their perspective, interest and/or critique of FAHF-2. A couple of the immunologist speakers were participants of the 2010 East-West Symposium organized by Mt. Sinai and Dr. Li that included FAHF-2 as a topic and included some specialized personnel from the FDA.

[LinksEtc]

That's so cool that your dh will be attending   

I'd be interested in learning what general topics they discuss here:
"The First Cross-strait Allergy and Asthma Forum (Mandarin)"

I'm not really interested in too many details, just the general ideas.

It's not a big deal if he can't attend that forum, but I figured I'd mention it.
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I wish I could get their opinions on the ideas in the asthma protocol thread .... I know, probably not appropriate .... but a girl can dream. 

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planned schedule with updates


[spoiler]Special Issue: Abstracts from the 2013 Asia Pacific Congress of Allergy, Asthma and Clinical Immunology, 14-17 November 2013, Taipei, Taiwan
November 2013

Best Paper Awards

Focus on tracks involving epigenetics, phenotypes/genotypes, AP population (sorry!), novel stem cell related research, microbiomes/disease/infection, updates from the anti-IgE guru. Socialization tasks include inquiries on FAHF-2 and traditional medicines used (or not) in AP region, and stem cell research. Special edition of newly published papers for this conference will be provided for attendees.


Thursday

• The First Cross-strait Allergy and Asthma Forum (Mandarin) if flight arrival in time otherwise ask for notes/recording

Friday

• Plenary Lecture (2) (3) (4) (5) Innate Immunity in Allergy and Autoimmune Diseases Ruby Pawankar
• Symposium (2) Sublingual Allergen Immunotherapy


• SLIT for Allergic Children, the Taiwanese Experience
• The Future of SLIT in Childhood Allergies Hugo Van Bever National University of Singapore Singapore
• Mechanisms of Allergen-Specific Immunotherapy Mübeccel Akdis Swiss Institute of Allergy and Asthma Research Switzerland


• Symposium (4)Biological Agents and Gene Therapy for Allergy and Autoimmune Diseases


• Production of High-Affinity Human Monoclonal Antibody Fab Fragment to the Human IgE - Xunjia Chen Fudan University China
• Anti-IL-20 Antibody for Inflammatory Diseases Ming-Shi Chang National Cheng Kung University Taiwan
• Amelioration of Experimental Rheumatoid Arthritis Models by Adenoviral or Lentiviral Vectors-Mediated Gene Transfer
• Satellite Symposium - Stallergenes SLIT R&D
• Symposium (5) Innate Immunity to Allergens
• Symposium (6/8) Immunological Cells and Biomarkers in Allergic Inflammation and Anaphylaxis and Management


• Symposium (6) - Immunological Cells and Biomarkers in Allergic Inflammation
• Symposium (8) - Anaphylaxis and Management
  
  • Anaphylaxis in China: Triggers, Clinical Features and Treatments
  
  Faculty Dinner (Museum Night) National Palace Museum (ooh-la-la! fancy!)
  
  Saturday
  
  • Plenary Lecture (6) (7) (8) (9) Environmental Allergy of Skin and Upper Airway
  • Symposium (11) Genetics and Epigenetics of Allergy and Asthma in AP Region
  • Satellite Symposium (6) Menarini (Italian pharm)
  • Symposium (16) Virus Infection, Microbiome, and Probiotics in Allergy
  • Forum (1) Regional Guideline for Food and Milk Allergy
    
  • Symposium (17) Phenotypes and Endotypes of Allergy and Asthma (Bone Marrow Progenitor Cells and Asthma)
  • Satellite Symposium (7) Abbott
  
  Gala Dinner and Farewell Party
  85F, Shinyeh 101, Taipei 101 (another ooh-la-la fancy dinner)
  
  Sunday
  
  • Plenary Lecture (10) (11) (12) (13) Allergy, Asthma and Immunity in a Changing World (Tse-Wen Chang, Updates on Omalizumab and Anti-CemX – Antibodies Targeting the IgE Pathway)
  • Symposium (19) ACAAI Sponsored Symposium: New Frontier of Allergy Diseases
  
  Closing Ceremony
  
  
  Persons to schmooze, ask re: FAHF-2, etc.
  
  Jiu-Yao Wang MD, D.Phil. (Oxon/Oxford), Division of Allergy and Clinical Immunology, Department of Pediatrics, College of Medicine, National Cheng Kung University

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[yelloww]

I'm interested to find out what they discuss in this one:

Symposium (5) Innate Immunity to Allergens

[CMdeux]

I'm super excited by this!!   

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Primer on Nancy Chang. She's still working in the US but she was co-founder of Tanox (Xolair) with her husband Chang Tse-wen who returned to Taiwan and will be at the conference. Whether or not she'll be there as an attendee I don't know.

Sit through the whole thing. Right around the 11:00 mark she starts to talk about her family's issues with allergies and what drove them to research allergy/asthma. WOW. This hits home on so many levels. I had no idea she is now an angel investor. What an incredible woman.

Women in Chemistry: Nancy Chang

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Collapsing to streamline.
[spoiler]

I'm interested to find out what they discuss in this one:

Symposium (5) Innate Immunity to Allergens

I was, too. Then it turned out to be mostly dust mites. It might be ignorance on my part maybe mechanism is more important than the allergen in question? It's on the schedule to attend at any rate.



Two significant connections I'd like to underscore are the goals to establish a direct contact with Dr. Jiu-Yao Wang, kind of a Taiwanese Sicherer (Taiwan, not Thailand, please no one feel bad if you didn't initially know the distinction), and Dr. Yin Jia, Peking Union Medical College Hospital, both attended 2010 EWAT with Dr. Li will also be at 2013 APCAACI. Anyhow, look at this 2010 East-West Scientific Symposia on Allergy & Traditional Oriental Medicine (EWAT).

Mission: Provide an opportunity for Western and Eastern medical scientists to exchange scientific progress on understanding food and environmental allergies, and on traditional and novel treatments and provide a bridge for international collaborations on translational and clinical research, which ultimately lead to new development for prevention and treatment of allergic disorders and improve people's health in the 21st century.

Note organizing committee members at 2010 EWAT:

Xiu-Min Li, MD – Executive Chair (USA) (FAHF-2/Sinai)
Hugh Sampson, MD – Co-Chair (USA)
Jiu-Yao Wang, MD, PhD – Committee Member (Taiwan)
Yin Jia, MD – Committee Member (China)

Sponsors 2010 EWAT:

Center for Chinese Herbal Therapy for Allergy and Asthma at Mount Sinai School of Medicine, NY, USA
Chinese Society of Immunology (will also present and sponsor 2013 APCAACI)
Food Allergy Initiative (back before FARE)

Consider some of these presentations at 2013 APCAACI

SLIT for Allergic Children, the Taiwanese Experience
Food Allergy: Allergencity of Carbohydrates– Unique Problem in Different Regions (Singapore)
Allergy an Emerging Epidemic: Sri Lankan Scenario
The Chinese Society of Immunology
Anaphylaxis in China: Triggers, Clinical Features and Treatments, Dr. Yin Jia

Then all various Asia-Pacific populations applicability and study of OIT, derm/atopy, asthma. So certainly in a population with access and understanding of pharmacognosy, why isn't it a huge part of the experience there with respect to relative geography as a region? Meaning why the heck isn't everyone going full bore on FAHF-2 if there are no concerns of patents, availability, understanding, acceptance.

OIT has kind of withered up, stem cell research is relatively limited in USA compared to AP region, what's left here in USA? It certainly bumps up FAHF-2 on the list, and on that I want the domestic Asia perspective for a baseline to compare with the FDA empirical data that emerges from USA.

I am keen to hear how allergy and anaphylaxis are managed and treated in mainland China, where TCM pharmacognosy is strongest in quality, standardization, and used within a complementary manner by Western medicine educated MDs. If ANYWHERE pharmacognosy is used for anaphylaxis wrt to TCM it's going to be mainland China. The presentation is by the very same researcher in attendance to the Mt. Sinai 2010 conference on TCM linked at top.

Only one paper Traditional Medicine in Allergic Diseases is published in the special edition conference publication. I can't find on the schedule anywhere it would be presented so I don't even think it's on any of the tracks. And this is given that we know there are committee and sponsor crossover from the Mt. Sinai organized 2010 Symposium on TCM/pharmacognosy in treatment of allergy.

To that end since I am in possession still of a bona fide private version of FAHF-2 dispensed by Dr. Li in person, I may have DH take it there to invite perspective on it from qualified professionals who were at the 2010 EWAT TCM Symposia.[/spoiler]

[CMdeux]

{rubs hands together}

This is going to be GREAT!!   

[twinturbo]

Initial thoughts from the conference:

The focus appears to understand cause and mechanism, the treatment side is more theoretical which is interesting, but a lot more abstract on what it means on treatment.

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I have posted the complete set of abstracts for all conference content at the following link:

https://dl.dropboxusercontent.com/u/11835087/APCAACI%202013%20Abstracts.zip

I can't test the link right now. Will try later.

Oh yeah it works. Good luck reading it's serious stuff.

So much... where to start.

CLINICAL SIGNIFICANCE OF DETECTABLE ALPHAGAL-SPECIFIC IGE IN INDIVIDUALS WITH UNDETECTABLE SPECIFIC IGE FOR MAMMALIAN MEATS IN MAMMALIAN MEAT ALLERGY FOLLOWING TICK BITES
SHERYL VAN NUNEN1, MONICA MASTROIANNI1, RICHARD FULTON1, SURAN FERNANDO1, ANTONY BASTEN2 1Royal North Shore Hospital, Australia 2The Garvan Institute of Medical Rsearch, Australia
Background: The association of mammalian meat-induced anaphylaxis and previous tick bites was first described by van Nunen et al in 2007. Individuals typically have demonstrable IgE specific for alphagal, and, almost invariably, for one or more mammalian meats (beef, mutton, pork). The spectrum of mammalian meat-induced allergic reactions provoked by previous tick bites comprises large local reactions at the site of previous tick bites following mammalian meat ingestion, gastro-intestinal symptoms following mammalian meat ingestion and/or delayed urticaria and/or angioedema, and delayed mammalian meat-induced anaphylaxis. This study examines the clinical significance of the detectable alphagal-specific IgE in those individuals who have no detectable IgE specific for any of the mammalian meats (beef, mutton, pork).
Methods: We reviewed the clinical histories of 9 patients with a history of allergic reactions following mammalian meat ingestion who had detectable alphagal-specific IgE in the absence of specific IgE for any mammalian meats tested in our laboratory (beef, mutton, pork). Results: These 9 patients with detectable IgE specific for alphagal and an absence of IgE specific for mammalian meats, had
> delayed anaphylaxis to mammalian meat (1/9)
> delayed urticaria and/or angioedema (7/9)
> gastro-intestinal symptoms alone (1/9)
> gastro-intestinal symptoms with delayed urticaria (1/9)
> large local reactions at the sites of previous tick bites after ingestion of mammalian meat/s (1/9)
Conclusion(s): In this group of individuals with specific IgE for alphagal and no detectable IgE specific for mammalian meats, any manifestation/s of the spectrum of allergic reactions may be seen, however, anaphylaxis appears to be both uncommon (11%), and less common than gastro-intestinal symptoms (22%), whilst delayed urticaria and/or angioedema (78%), is the most common reaction type. Crucially, the cause of the allergic reactions in all 9 of these patients would have remained unconfirmed if the presence of alphagal-specific IgE had not been sought.

Investigation into the potential of shrimp OIT.

Conclusion(s): The IgE-binding epitope mapping data of shrimp tropomyosin were used to generate the hypoallergenic derivatives MEM49 and MED171. With a significant reduction in allergenicity and high capacity in inducing IgG blocking antibodies, both mutants exhibit the potential in immunotherapy of shrimp allergy.

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ORAL IMMUNOTHERAPY FOR MILK ALLERGY INCREASES THE FREQUENCY OF CD4+NKG2D+ T CELLS AND CD4+CD25-CD127- T CELLS IN PERIPHERAL BLOOD
YUZABURO INOUE1, KOKI CHIBA1, IZUMI KATO2, YOSHINORI MORITA2, AKIKO YAMAIDE3, SHUICHI SUZUKI4, TAKAYASU ARIMA1, MINAKO TOMIITA3, AKIRA HOSHIOKA3, NAOKI SHIMOJO1

1Chiba University, Japan 2Chiba Kaihin Municipal Hospital, Japan 3Chiba Children's Hospital, Japan 4Ational Shimoshizu Hospital, Japan

Background: Oral immunotherapy is considered as one of the curative treatments for food allergy. However, the detailed mechanisms of the effect of the therapy such as induction of peripheral tolerance through the generation of regulatory T cells are still unclear. In this study, we focused on changes in frequency of various known IL-10-producing T cells during rush oral immunotherapy for food allergy.

Methods: Nine children (age, 5-10 years) with IgE-mediated cow's milk allergy confirmed by positive double- blind, placebo-controlled food challenge received oral immunotherapy. Informed consent was obtained from their parents or guardians.

After an escalation phase for 2-3 weeks, all patients achieved a daily maintenance dose (200 ml). We collected bloods from the patients before the escalation phase, on day 7, after the escalation phase and after 2 months and 6 months of the maintenance therapy. We analyzed the changes in frequency of IL-10-producing CD4+ T cells (CD25-LAP+CD4+ T cells, NKG2D+CD4+ T cells and CD25-CD127-CD4+ T cells) by flow cytometry.
Results: The frequency of both CD4+NKG2D+T cells and CD25-CD127-CD4+ T cells significantly increased in the maintenance phase but not in the escalation phase. The frequency of CD25-LAP+CD4+ T cells was not changed during the therapy.

Conclusion(s): Our data suggest that CD4+NKG2D+ T cells and/or CD4+CD25-CD127- T cells may have a role in the effects of oral immunotherapy for food allergy.

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ANTIBODIES TARGETING CH4-CEMX JUNCTION FOR DOWN-REGULATING MIGE-B LYMPHOCYTES
CHIEN-JEN LIN, NIEN-YI CHEN, JIUN-BO CHEN, YU-YU SHIUNG, ALFUR FU-HSIN HUNG, CHIEN-SHENG LU, PHEIDIAS C. WU, HSING-MAO CHU
Academia Sinica, Taiwan

Background: IgE plays central roles in the pathogenesis of various IgE and mast cell-mediated diseases, as the IgE pathway has been validated to be an effective therapeutic target by the successful development of Omalizumab (Xolair). Monoclonal antibodies (mAbs) that can target membrane-bound IgE (mIgE)-expressing B lymphoblasts and memory cells are new potential therapeutic candidates. The discovery of CemX, a discrete domain of 52 aa residues located between the CH4 domain and the C-terminal transmembrane anchor peptide of mIgE offers opportunities to develop mAbs specific for mIgE. Two CemX-specific mAbs, 4B12 and 47H4, which can cause the lysis of mIgE-B cells by apoptosis and antibody-dependent cellular cytotoxicity (ADCC), have been previously reported.

Methods: In this study, by using virus-like particles formed by hepatitis B virus core antigen that harbors part of C-terminal segment of CH4 and part of the N-terminal segment of CemX as immunogen, we have identified mAbs that bind to the junction of CH4 and CwmX of mIgE. Results: The mAb 5A8 binds to a 17 aa epitope, SVNPGLAGGSAQSQRAP, which cannot be recognized by 4B12 and 47H4. In addition, 5A8 can lyse mIgE-expressing B cell lines by apoptosis and ADCC.

Conclusion(s): These studies have thus identified a novel antibody candidate for targeting the IgE pathway for the treatment of allergic diseases.

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DEVELOPING ANTIBODY DRUGS TO TARGET CEMX OF MIGE FOR THE TREATMENT OF ALLERGIC DISEASES
YUEH-HSUAN CHAN1, HSING-MAO CHU2, JIUN-BO CHEN2, PHEIDIAS C. WU1, HUNG-WEN CHOU1, CHAU-HONG LI1, TIEN-TIEN CHENG1, NIEN-YI CHEN1, CHI-CHUN PAN1, WILLIE LIN1
1Fountain Biopharma Inc., Taiwan 2Academia Sinica, Taiwan

Background: CemX is a discrete domain of 52 a.a. residues, located between the CH4 domain and the C-terminal membrane anchor peptide of the e heavy chain of membrane-bound IgE (mIgE) on human B lymphocytes. Antibodies that target CemX fragments are therefore product candidates for controlling IgE production for treating allergic diseases.

Methods: Among the monoclonal antibodies (mAbs) prepared for their ability to bind to CemX fragments or CemX-containing recombinant proteins in ELISA, those that can bind to native mIgE on B cells can cause ADCC, apoptosis, and other cytolytic mechanisms on the B cells in culture or in mouse models.

Results: The CemX-specific mAbs prepared previously appear to recognize discrete and overlapping peptide segments of CemX. While the peptide epitopes recognized by two mAbs may be adjacent to each other and overlap, the two mAbs do not bind to the adjacent epitopes by a substantial degree. This can be illustrated by the pair of humanized mAbs, h4B12 and h47H4. The mAb h4B12 binds to peptide P1-15 (GLAGGSAQSQRAPDR) and h47H4 binds to peptide P7-18 (AQSQRAPDRVLC). Although the two epitopes share a segment AQSQRAPDR, the mAb h4B12 does not bind to P7-18, and h47H4 does not bind to P1-15.

Conclusion(s): The mAb h4B12 can target mIgE+ B cells directly and inhibit the synthesis of IgE, and is thus an attractive drug candidate. We have now developed a transfected CHO cell line producing high yield of h4B12 in preparation for carrying out human clinical trials.

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SYMPTOMS IMPROVEMENT OF SUBCUTANEOUS IMMUNOTHERAPY IN CHILDREN WITH MULTIPLE ALLERGIES
ZAHRAH HIKMAH, ANANG ENDARYANTO, ARIYANTO HARSONO
Soetomo Hospital, Indonesia

Background: House dust mite subcutaneous immunotherapy (HDM-SCIT) is a treatment for allergic disease because it provides symptomatic relief while modifying the allergic disease by targeting the underlying immunological mechanism. SCIT consist of a series of graded doses of allergen administered subcutaneously at increasing intervals for a variable duration. Previous study showed that HDM-SCIT could reduce the symptoms of allergy caused by mite allergen. Some children not only suffer from mite allergy but also others like food and animal fur (multiple allergies). This study evaluates the improvement in symptoms of multiple allergies children treated with SCIT for one year.

Methods: The prospective cohort study was done in allergic division pediatric department of Dr. Soetomo Hospital from July 2011 – June 2013 in 53 children with allergy to HDM plus food or/and animal fur allergies. Parental consents were taken. Subjects received HDM-SCIT for 3 years. The series were divided into 5 series. This study only evaluated until 3rd series. Subjects were also trained to conduct dietary elimination of suspected allergens. The symptoms and its causes were recorded every visit.

Results: The most common symptoms were respiratory symptoms (94%), skin symptoms (21.5%), and gastrointestinal symptoms were the least (6.1%). There were significant improvement of mite causes symptoms of children receiving SCIT almost in each series compared with the 1st series and the series before (p<0.05), others causes symptoms weren't improved significantly. At the 1st and 2nd series, mite causes symptoms still dominated. In the 3rd series, food is the higher causes of symptoms.

Conclusion(s): SCIT provides symptomatic improvement in children with mite allergy accompanied with food or/and animal fur allergies. Dietary elimination of suspected allergens should be conducted properly to improve the result of SCIT in children with mite allergy accompanied with food or/and animal fur allergies.

UTILIZATION OF A DERMATOPHAGOIDES PTERONYSSINUS AND D. FARINAE MIX FOR SPECIFIC IMMUNOTHERAPY OF MITE ALLERGIC PATIENTS
RIAD FADEL1, THIERRY BATARD1, VERONIQUE BODO1, JULIEN BOULEY1, MAXIME LE MIGNON1, SEBASTIEN BRIERE1, PHILIPPE MOINGEON1, EMMANUEL NONY1, TIM CHEW FOOK2
1Stallergenes, France 2National University of Singapore, Singapore

Background: HDM-allergic patients are coexposed and cosensitized to the two common mite species D. pteronyssinus and D. farinae. On the basis of seroepidemiological studies, we investigated whether the optimal product to desensitize those patients should encompass extracts made from one or the two species, and bodies with/without feces.

Methods: Using ImmunoCap, Vidas and ImmunoSolid-Phase AllergenChip methods, we assessed patterns of IgE sensitization in sera from ~800 HDM-allergic adult patients from Europe, US, Canada, Japan. We identified the allergens found in bodies and feces purified from the two mite species.

Results: IgE reactivity was tested against natural extracts, purified Der p 1 and 2, Der f 1 and 2 as well as group 4-10 and 14 allergens from the two species. Irrespective of the geographical area, patients exhibit comparable patterns of IgE sensitization, with group 1 and group 2 allergens confirmed as major allergens. Reactivity with species-restricted IgE epitopes were commonly observed for both major and minor allergens. Mass spectrometry analyses revealed that bodies from D. pteronyssinus contain high amounts of group 2 and 20 allergens, whereas feces bring group 1, 5, 8-10, 13 and 21 allergens. Bodies from D. farinae are enriched in group 3, 14 and 20 allergens and feces in group 1, 5, 7, 9, 13, 21 and 22 allergens.

Conclusion(s): This analysis of patterns of IgE sensitization conducted in 800 patients from Asia, Europe, North America establishes that most patients have IgE directed to (i) species-restricted epitopes, (ii) feces- and body-associated allergens. As a consequence, we conclude that HDM extracts for desensitization should be prepared from both D. pteronyssinus and D. farinae species, and include bodies and fecal particules. The latter extends the repertoire of allergens and derived epitopes, thus recapitulating natural exposure conditions.

A NOVEL IMMUNOMODULATING PEPTIDE FOR ATTENUATION OF HOUSE DUST MITE-INDUCED ASTHMA
YU-ROU WU1, TING-YU CHEN1, LIN-SHIEN FU2, SHUN-LUNG FANG1
1National Tsing Hua University, Taiwan 2Taichung Veterans General Hospital, Taiwan

Background: Asthma is a common chronic inflammatory disease characterized by reversible airflow obstruction and airway hyperresponsiveness (AHR). Conventional therapy for asthma usually alleviates allergic symptoms using bronchodilators, corticosteroid, anti-histamines, and leukotriene antagonists. However, some patients with severe asthma are poorly controlled, suggesting that they need more advanced therapies. Recently, we have discovered and identified a novel immunomodulating peptide (CPPecp), and it is able to target epithelial cells in vitro and in vivo by recognition of cell surface heparan sulfate proteoglycans.

Methods: We have investigated that asthmatic airway inflammation related gene expression profiles in Beas-2B cells (airway epithelial cells), and demonstrated a mite-induced asthma mouse model to evaluate effects of CPPecp mediated immunomodulation in vivo. Physiological functions including pause enhancement (Penh), lung histopathology, serum mite-specific antibodies in the absence and presence of CPPecp were analyzed.
Results: CPPecp down-regulated gene expression levels of a few inflammation related proteins, indicating that CPPecp played a critical role in regulating inflammatory response of bronchial epithelial cells in vitro. In addition, CPPecp itself did not influence gene expression of chemokines, and proinflammatory cytokines in Beas-2B cells. Administration of CPPecp in asthmatic mice showed significant reduction in airway AHR and decrease in asthma-related cytokine expression, suggesting that CPPecp reduced HDM-induced airway inflammation in vivo.

Conclusion(s): Our data demonstrated that CPPecp attenuated development of allergic airway inflammation and AHR in vitro and in vivo, possibly through inhibition of inflammation related protein expression in the inflammatory lung tissues. These findings facilitate development of our CPPecp as a non-steroid agent in pulmonary inflammation treatment for translational medicine.