QuoteChina

ANAPHYLAXIS IN CHINA: TRIGGERS, CLINICAL FEATURES AND TREATMENTS
Background:

Anaphylaxis incidence is increasing. Little is known about the clinical features and triggers of anaphylaxis in China.

Methods:
We performed a review of clinical records for anaphylactic reactions over 10 years.

Results:
We identified 1008 anaphylactic reactions in 438 patients (222 male patients). 311 patients had recurrent reactions. The median age at time of the first reaction was 30 years (age range, 10 months to 70years). The skin (83.8%) was the most frequently affected organ followed by the respiratory system (68.6%) and cardiovascular system (56.3%). The triggers included food (79.2%), drugs (6.8%), insect (0.3%) and "others" (13.4%). Wheat was the culprit agent of food in 36.4% anaphylactic reactions. Traditional Chinese medicine (1.7%) was the most common cause of drug-induced anaphylaxis. 637(63.2%) reactions were managed in Emergency department, corticosteroid (26.6%) were more often administered than adrenaline (8.3%).Children were more often presented with respiratory symptoms compared with adults (80.1% vs. 64.9% P<0.001) .Fruits /vegetables were more common food triggers in children than in adults(16.5% vs.10.3% p=0.01) , whereas adults were more frequently sensitive to cereals compared with children (45.9% vs.34.5%,P=0.002) .Drug-induced anaphylaxis were more common in adults than in Children(8.2% vs.2.5%,p=0.003).

Conclusions:
The present study indicates that the most common symptoms of anaphylaxis in China were skin presentations. Respiratory presentations are more frequent in children. Food is the main trigger in anaphylaxis just as in the West, but shows a different picture, fruits /vegetables and cereals are common food triggers in children and adults respectively. Adrenaline is used in a minority of anaphylactic reactions.

QuoteTraditional Chinese medicine (1.7%) was the most common cause of drug-induced anaphylaxis.

QuoteJapan
INFLUENZA VACCINE-INDUCED ANAPHYLAXIS: PIVOTAL ADVANCE IN IDENTIFICATION OF THE CAUSE

In the 2011/12 season, the incidence of influenza vaccine-associated anaphylaxis (IVA) was significantly higher than the average annual incidence in past years in Japan. IVA has been related to egg allergy since influenza vaccines are produced in embryonated eggs, however, most of the patients did not have egg allergy. We then investigated the cause of IVA by measuring specific IgE antibodies to various vaccine components and performing the basophil activation test (BAT). The "common belief" of egg protein-induced IVA was overturned by this novel approach.

Methods: We collected serum and blood specimens of IVA cases within 2 months after the events from all areas of Japan. The diagnosis was confirmed based on the Brighton collaboration case definition of anaphylaxis of level 1 and 2. Twenty cases of the confirmed IVA were examined and age-matched 15 healthy children and 8 egg allergy children with the similar vaccination history served as controls. Specific IgE to each component, namely A/H1, A/H3 and B, of the trivalent vaccines distributed for 2011-12 season from several vaccine manufacturers was measured with ELISA. Antigen-induced basophil activation was evaluated by measurement of CD203c expression with flowcytometry. Effects of additives in the vaccine preparations on the CD203c expression were also examined.

Results: Specific-IgE antibodies to A/H1, A/H3 and B were significantly elevated in patients with IVA than in controls. Influenza vaccine component-induced CD203c expression in basophils were also highly enhanced in IVA and no response was observed in control. Since the IVA cases segregated in patients who received phenoxyethanol-containing vaccines, effect of the preservative on basophil activation was examined and enhancement with phenoxyethanol, not with thimerosal, of the response was observed.

Conclusions: The results suggest that the recent IVA in Japan was caused by specific IgE antibodies to influenza vaccine components and that phenoxyethanol may have modified the reaction. Measurement of vaccine-component –specific IgE and BAT is useful for diagnosis of vaccine-associated anaphylaxis.

QuoteKorea
GENETICS AND EPIGENETICS OF ALLERGY AND ASTHMA IN KOREAN CHILDREN

The prevalence of allergic diseases such as asthma, allergic rhinitis and atopic dermatitis has risen markedly in Korea, thus it is necessary to understand the etiologies, risk factors, and natural courses.

Over the last half century, lifestyle has changed and it has contributed to a considerable increase of allergic diseases in Korea. The lower prevalence of allergic diseases and atopy was associated with life styles such as farming, exposure to farm animals during pregnancy, breast feeding and older siblings. Also, the risk of current AR increased in subjects with GA or AA at IL-13(+2044) when they were exposed to mold in the home during infancy compared with subjects who have GG IL-13(+2044) and had not been exposed to mold. The hygiene hypothesis was adapted to the microbiota hypothesis, which proposed that lifestyle factors in early life alter the composition of the gut microbial flora, thereby affecting the development of mucosal immune tolerance. The synergistic risks between caesarean delivery, formula feeding, and antibiotic use affect on the prevaleces of asthma, allergic rhinitis and atopy. Additive analysis revealed that the adjusted odds ratio (aOR) of allergic rhinitis for subjects with the IL13 AG+AA genotype was highest when all three of early life factors were present. In addition, infants born by cesarean section had 2-fold higher odds of atopic dermatitis at 12 month of age than those born by vaginal delivery, and the infants with CD14 TC+CC genotype and cesarean section also showed higher risk to develop atopic dermatitis from COCOA birth cohort.

Renovation during prenatal period increased a risk of cord blood IgE response and AD at 1 year of age interacting with innate immunity and ROS related genes. Also, home remodeling during pregnancy may affect the development of atopic dermatitis through the epigenetic changes from the COCOA birth cohort study. These findings suggest that the environmental changes during pregnancy may affect the development of AD by the gene-environment interaction and epigenetic mechanism.

In summary, increase of allergic diseases in Korea may be originated from the multiple independent environmental risk factors in critical susceptible period and genetic susceptibility. In addition, gene and environment interaction or epigenetic change may be involved in the development of allergic diseases.

QuoteSingapore
FOOD ALLERGY : ALLERGENCITY OF CARBOHYDRATES – UNIQUE PROBLEM IN DIFFERENT REGIONS

Our understanding that allergic responses to food are directed against mainly protein epitopes have recently been challenged. Recent studies demonstrates that IgE antibodies directed against carbohydrate moieties have been investigated in several studies in recent years.
This phenomenon has first been described against an oligosacharide galactose-alpha 1,3-galactose (alpha –gal) mainly in a geographical region that spanned the South Eastern parts of the United States since 2009. However awareness of this new clinical entity, has resulted in new cases identified in France and in Spain.

In Asia since 2009, there has been a series of cases following ingestion to a commercially manufactured prebiotic galacto-oligosacharide (GOS) that is found commonly in commercial milk formulas/beverages. The first reports from Vietnam suggests that the introduction of a new GOS containing beverage resulted in a spate of allergic reactions temporally associated with consumption of this beverage. We have seen in our Singapore a series of young children and adult presenting with anaphylaxis related to consumption of GOS containing commercial milk formulas. Interestingly, GOS is a functional food, and has been used as a supplemental prebiotic in food products and drinks in Europe and Japan since the 1980s, and was approved for supplementation in infant formula in Europe since December 2001. There has been no known reports of GOS containing beverages unlike the increased in allergic reactions associated with the arrival of these products to specific regions in Asia.

We present a novel concept of IgE mediated hypersensitivity to a unique carbohydrate GOS that appears to be have a distinct geographical footprint in Asia. The immunological data suggests that specific fractions of GOS (DP=degrees of polymerization) were more likely to induce basophil activation in-vitro. More studies need to be carried out to delineate the mechanisms as well as identify the primary sensitizer in this unique allergy.

QuoteJapan
ORAL IMMUNOTHERAPY FOR FOOD ALLERGY

Basic strategy for management of food allergy is to avoid the offending food for the security of diet. But the Japanese guidelines for food allergy recommend the policy of "minimal avoidance based on the precise diagnosis". In other words, we are trying to instruct patients to "eat as much as possible".

This policy has to be based on the result of an oral food challenge testing (OFC) to determine the safety level of allergen consumption for each patient. We have reported that these diet instructions were more effective on the earlier development of tolerance compared to the conventional food elimination. In other words, consumption of small amount of allergenic food promotes the natural outgrowth.
But patients with severe food allergies have the risk of anaphylaxis after eating trace amount of allergenic food. Oral immunotherapy (OIT) is targeting these patients not only for the achievement of tolerance, but more importantly, for the avoidance of unexpected severe reactions caused by an accidental exposure.

OITs are categorized into rush and slow protocols. Rush OIT has an induction phase to increase the allergen dose rapidly, which is conducted in-hospital setting for several days to weeks. Slow OIT is generally conducted at home to gradually increase the amount of allergen consumption for several months. Both protocols are followed by the maintenance phase to keep the tolerant dose.
Although many studies have reported considerably good results with 70 to 80 % of successful cases, no reports were free from concerns about safety. Even in the maintenance phase, severe reactions may be provoked in association with a sick or tired day, pollen season, irregular taking schedule, and exercise or bathing after consumption. For those safety reasons, OIT is still placed as an experimental trial, but is not recommended as a regular clinical practice.

QuoteCOMPARISON OF SPECIFIC IGE ANTIBODIES TO WHEAT COMPONENT ALLERGENS IN TWO PHENOTYPES OF WHEAT ALLERGY
YOUNG-HEE NAM1, EUI-KYUNG HWANG2, HYUN JUNG JIN3, JEONG MIN LEE2, YOO-SEOB SHIN2, YOUNG-MIN YE2, ARANTXA PALACIN4, GABRIEL SALCEDO4, SOO-YOUNG LEE2, HAE-SIM PARK2
1Dong-A University, South Korea 2Ajou University, South Korea 3Yeungnam University, South Korea 4Unidad De Bioquimica, Spain

Background: Clinical manifestation of wheat allergy are various according to the sensitization routes. Specific IgE to gliadin was proposed a marker for wheat dependent exercise induced anaphylaxis (WDEIA), while Tri a 14 was found to induce IgE response in baker's asthma.
To evaluate whether these components could be used for discriminating two major phenotypes of wheat allergy, anaphylaxis and/or urticaria and baker's asthma.

Methods: Twenty-nine patients with wheat allergy and 30 non-atopic healthy controls were enrolled from Ajou University Hospital. Group I included wheat-induced anaphylaxis and/or urticaria (n = 21) and group II included baker's asthma (n = 8). Total serum IgE levels and serum-specific IgE levels to wheat and gliadin were measured using the ImmunoCAP system, and serum-specific IgE to Tri a 14 by ELISA.
Results: The positive rate of skin prick test to wheat and serum-specific IgE to wheat was higher in group II than in group I, 41.7% vs. 75% and 71.4% vs. 87.5%, respectively. The prevalence of serum specific IgE to Tri a 14 was higher in group II (25%) than in group I (4.8%), while the serum specific IgE to gliadin was significantly higher in group I (70%) than in group II (12.5%). The cutoff value for predicting the baker's asthma using the ratio of serum specific IgE to Tri a 14 to gliadin was 742.8 with 87.5% sensitivity and 83.3% specificity.

Conclusion(s): The sensitization rate to Tri a 14 was very low in patients of two major phenotypes of wheat allergy in an Asian population. These finding suggest that the ratio of serum specific IgE to Tri a 14 to gliadin may be a potential candidate marker for predicting the phenotype of baker's asthma with high sensitivity and specificity.

QuoteASSOCIATION OF MANNOSE-BINDING LECTIN WITH WORK-RELATED RESPIRATORY SYMPTOMS IN BAKERY WORKERS EXPOSED TO WHEAT FLOUR
MI-AE KIM, MOON KYUNG YOON, EUN-MI YANG, HYE-SOO YOO, SEUNG-HYUN KIM, YOO SEOB SHIN, YOUNG-MIN YE, DONG-HO NAHM
Ajou University, South Korea

Background: In order to investigate an innate immunity, we evaluated the role of mannose-binding lectin (MBL), one of the initiation components of complement cascade, in the mechanism of baker's asthma.

Methods: A total of 385 bakery workers were included and subjects' clinical data and questionnaires regarding work-related respiratory symptoms were collected. Serum specific IgE, IgG1, IgG4 to wheat flour and MBL were measured by ELISA and four MBL2 genes (-226G/A in the exon 1, -225G/C, -431A/C, and -554G/C in the promoter) were genotyped. Results: Mean age was 34.9±7.7 and male consisted 56.5%, smoker for 41.8%. Mean working period was 4.0±3.5 years and low exposure group consisted 28.2%, intermediate exposure group for 31.9%, high exposure group for 36.3%. 66 subjects (17.1%) had work-related respiratory symptoms. Atopy was observed in 132 subjects (34.2%) and positive skin prick test to wheat flour was observed in 32 subjects (8.3%).

Mean MBL level was 797.1±410.1 ng/ml in which the workers with work-related respiratory symptoms showed significantly higher level than those without it (899.0±468.2 vs. 769.0±389.8, p=0.019). After multivariate analysis, positive skin prick test to wheat flour and MBL level were the only statistically significant parameters for predicting work-related respiratory symptoms (p=0.001, p=0.008, respectively). A total of four polymorphism of MBL2 genes were significantly related to MBL level and haplotype 1 [GGAG], haplotype 2 [AGAC] were also significantly related to MBL level. No significant associations were found between MBL level and atopy, serum specific IgE and IgG4 antibodies. In vitro study, albumin increased MBL production in human lung epithelial cells, monocytes, and hepatocytes as dose-dependent manners.

Conclusion(s): The MBL, a component of innate immunity may contribute to develop work-related respiratory symptoms in bakery workers where the promoter polymorphisms of MBL2 gene could affect serum level of MBL.

QuoteSYMPTOMS 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.

QuoteUTILIZATION 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.

QuoteA 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.

QuoteDEVELOPING 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.

QuoteANTIBODIES 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.

QuoteORAL 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.

Quote
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

QuoteCLINICAL 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.

QuoteConclusion(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.

QuoteThe 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.