The complex link of the environment on allergic rhinitis and atopic dermatitis
Kiat Ruxrungtham


Review article
Mucosal-associated invariant T cells in clinical diseases
Rangsima Reantragoon, Norasate Boonpattanaporn, Alexandra Jane Corbett, James McCluskey

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial infection via vitamin metabolites. The discovery of MAIT cells in the past two decades and the recent discovery of MR1 ligands has opened a new field and potential area for cellular immunotherapy using these unique cells. Their evolutionary conservation in mammmals underscore their biological role in the host. In the past two years, we have been involved in the generation of MR1 tetramers as a tool for identification of these cells. Many groups have studied the role of these cells in clinical diseases.
Objective: Here, we provide an up-to-date comprehensive review of clinical disease that have been studied with regards to MAIT cells.
Results: Original articles and review articles under the topic of MAIT cells and their relation to clinical diseases, both in human and animal models were included in the review.
Conclusion: MAIT cells are potential candidates for future cellular immunotherapy. However, more understanding of the biological role of MAIT cells need to be elucidated first.


Original articles

An association and meta-analysis study of 4 SNPs from beta-2 adrenergic receptor (ADRB2) gene with risk of asthma in childrenXingqing Guo, Hongying Zheng, Chenggang Mao, Enben Guan, Hui Si

Background: Although various case-control studies have been conducted to investigate the relationship between ADRB2 gene polymorphisms and asthma risk in different population groups, the results have been conflicting and inconclusive.
Objective: We performed a case-control study to investigate the association of 4 SNPs in the ADRB2 gene with risk of asthma in children, and then conducted a meta-analysis by combining the previous studies.
Methods: A total of 340 patients and 340 age-matched healthy controls were recruited. All of the subjects were genotyped using the PCR-based invader assay. The case-control study was performed to define the contribution of rs1042713, rs1042714, rs1800888, and rs1042711 to the predisposition of asthma. Additionally, we further conducted a meta-analysis of the study findings together with those of previously reported studies.
Results: No significant association was found between the polymorphisms rs1042713, rs1042714, rs1800888, and rs1042711 and asthma in the current case-control study. The meta-analysis confirmed that there was no positive association of these SNPs with asthma in children in Asia, South America, Europe and the overall population.
Conclusions: None of the four polymorphisms in ADRB2 gene were associated with a risk of asthma in a current children population.


Association between environmental factors and hospital visits among allergic patients: A retrospective study
Jie Chen, Li Peng, Shan He, Youjin Li, Zhe Mu

Objective: This study investigated correlations between meteorological and environmental factors (MEFs) and allergic rhinitis in childhood (ARC).
Methods: Children who received treatment for AR and meteorological data that might have influenced AR in the same time period were included in this study. Daily average maximum values of sodium dioxide (SO2), nitrogen dioxide (NO2), and particulate matter (PM10) at 3 a.m. and 8 a.m. were provided by the Shanghai Environmental Bureau for statistical analysis using a generalized additive model (GAM).
Results: Outpatient visits for ARC were higher, with a bimodal shape, for daily average temperatures of about 11°C and 21°C. However, increasing humidity was associated with a downward trend in outpatient visits for ARC, suggesting that high humidity had a protective effect on AR. When levels of air pollutants such as O3, SO2, and PM10 increased by 10 μg/m3, AR outpatient visits increased by 1.95%, 1.19% and 0.33%, respectively, suggesting that air pollution might increase the risk of AR episodes.
Conclusions: MEFs were significantly correlated with the incidence of ARC.


The effectiveness of oxymetazoline plus intranasal steroid in the treatment of chronic rhinitis: A randomised controlled trialTorpong Thongngarm, Paraya Assanasen, Panitan Pradubpongsa, Pongsakorn Tantilipikorn

Background: The recommended drug for moderate to severe chronic rhinitis is intranasal steroids (INS). However, nasal congestion could be refractory and need additional treatments.
Objective: We sought to explore the benefit of oxymetazoline (Oxymet) plus INS on nasal congestion without inducing rhinitis medicamentosa.
Methods: We performed a 6-week, randomised, double-blind clinical trial in 50 patients, 18 years of age or greater, with chronic rhinitis who had used INS and cetirizine and still had nasal congestion. Subjects were randomised to receive 2 sprays of 0.05% Oxymet in each nostril twice daily or placebo for 4 weeks. All patients received 2 sprays of budesonide (100 mg/spray) in each nostril twice daily and 10 mg cetirizine once daily from entry throughout the study. Nasal symptom scores, nasal peak inspiratory flow (NPIF) and Rhinoconjunctivitis Quality of Life (Rcq) scores were measured.
Results: Oxymet significantly reduced nasal congestion in subjects with chronic rhinitis compared with placebo on the day of 15-28 and 29-42. In subjects with allergic rhinitis, nasal congestion scores in the Oxymet group were significantly reduced compared with those in the placebo group on days 4-7, days 8-14, days 15-28 and days 29-42. In the Oxymet group, post hoc analysis showed that subjects with allergic rhinitis significantly improved their nasal congestion scores compared to non-allergic individuals. The combination of INS and Oxymet was not associated with rhinitis medicamentosa.
Conclusions: The combination of INS and Oxymet provides additional benefit compared to INS monotherapy in relieving nasal congestion in subjects with chronic rhinitis and allergic rhinitis without developing rhinitis medicamentosa.


A preliminary study of intranasal epinephrine administration as a potential route for anaphylaxis treatment
Chatchawan Srisawat, Kanittha Nakponetong, Patchanee Benjasupattananun, Chanthana Suratannon, Leatchai Wachirutmanggur, Siribangon Boonchoo, Duangjai Pankaew, Apirom Laocharoenkiat, Punchama Pacharn, Orathai Jirapongsananuruk, Nualanong Visitsunthorn, Pakit Vichyanond


Background: The intranasal (IN) administration of epinephrine could be an alternative route for anaphylaxis treatment. Although IN epinephrine absorption has been demonstrated in animals, such data in humans are still lacking.

Objective: To study the pharmacokinetics of IN epinephrine absorption in humans.

Methods: Each healthy adult (n=5) was administered IN saline, IN epinephrine at various doses (i.e., 0.3, 0.6, 1.25, 2.5 and 5 mg), and intramuscular (IM) epinephrine at 0.3 mg. Plasma epinephrine levels at baseline and various time points up to 120 minutes after administration were determined using high-performance liquid chromatography with electrochemical detection.

Results: Significant systemic absorption of epinephrine via IN route was observed only at the dose of 5 mg, and the absorption thereof was comparable to that of IM epinephrine; the average area-under-curve (AUC) values at 0-120

minutes for IN saline, IM epinephrine, and 5 mg IN epinephrine were 0.3, 18.3, and 19.4 ng.min/mL, respectively. In addition, the peak epinephrine concentrations and the time to reach them were also not significantly different between IM and 5-mg IN epinephrine; the corresponding values (mean ± SD) were 309 ± 88 pg/mL and 67 ± 43 min for IM epinephrine, and 386 ± 152 pg/mL and 70 ±17 min for 5 mg IN epinephrine.

Conclusion: This preliminary study showed that epinephrine can be significantly absorbed via the IN route in humans. However, it requires a higher IN dose (5 mg) than the usual IM dose (0.3 mg) to achieve comparable systemic epinephrine absorption.humans. However, it requires a higher IN dose (5 mg) than the usual IM dose (0.3 mg) to achieve comparable systemic epinephrine absorption.


Anaphylactic reactions in adult patients in Southern Israel
Inna Hananashvili, Noga Givon-Lavi, Carmi Bartal, Arnon Broides

Background: Southern Israel is inhabited by Jews and Bedouins. Children from these populations differ in the epidemiology of anaphylactic reactions; however, the effects of ethnicity on the epidemiology of anaphylactic reactions in adults in these populations are unknown.
Methods: Retrospective review of medical records of patients with anaphylactic reactions treated in a single institution during 2008-2012.
Results: A total of 192 evaluable cases of anaphylaxis were recorded; 155 (80.7%) anaphylactic reactions occurred in Jews and 37/192 (19.3%) occurred in Bedouins. A trend towards an older mean age of occurrence of anaphylaxis was recorded in Jewish patients compared with Bedouin patients: 48.1 years versus 41.2, respectively (P = 0.053). Anaphylaxis was more common in Jewish female patients than males and more common in Bedouin male patients than females. Overall, 93/155 (60.0%) females in Jewish patients were affected compared with 14/37 (37.8%) in the Bedouin population (P = 0.015). More Jewish patients had more anaphylaxis attributed to food compared with Bedouin patients: 31/155 (20%) versus 2/37 (5.4%) (P = 0.034). The mean yearly incidence of anaphylaxis was similar in Bedouin and Jewish patients: 12.1 ± 5.3 versus 17.6 ± 15.3, respectively (P = 0.466). However, a significant trend towards a higher incidence of anaphylactic reactions was recorded throughout the study years only in Jewish patients (r = 0.906, P = 0.034).
Conclusions: Adult Jewish patients have a significantly higher probability of having anaphylactic reactions due to food compared with Bedouin patients, with females being more affected, and the incidence of anaphylactic reaction is increasing only in the Jewish population. The epidemiology of anaphylactic reactions can differ between populations residing in the same geographical area.


Allergenicity of native and recombinant major allergen groups 1 and 2 of Dermatophagoides mites in mite sensitive Thai patients
Nitat Sookrung, Jintarat Choopong, Watee Seesuay, Nitaya Indrawattana, Wanpen Chaicumpa, Anchalee Tungtrongchitr

Background and objective: Natural allergenic extracts using for diagnosis and immunotherapy may have batch-to-batch variations and contaminations with unrefined allergens or non-allergenic components. Thus, recombinant allergen is believed to overcome these shortcomings. In this study, native and recombinant allergens of group 1 and 2 of Dermatophagoides mites were produced and their allergenicities were compared.
Methods: Native allergens were prepared by MAb affinity chromatography. All recombinant allergens were produced in E. coli expression system. IgE reactivities of these allergens were determined by IgE-ELISA.
Results: The native and recombinant Der p 1, Der p 2, Der f 1, Der f 2 had molecular weights of approximately 25, 15, 25 and 15 kDa, respectively. IgE reactivities of nDer p 1, nDer f 1, rDer p 1 and rDer f 1 were 96.67%, 90%, 43.33% and 46.67%, respectively. Allergenicities of nDer p 2, nDer f 2, rDer p 2 and rDer f 2 were 86.67%, 96.43%, 76.67% and 89.29%, respectively. The findings indicated that recombinant group-1 products were minor allergens which revealed no correlation with their native forms. In contrast, recombinant group-2 allergens were major allergens and showed a significant correlation to their native allergens.
Conclusion: We successfully produced native and recombinant group-1 and group-2 allergens. According to their allergenicities, recombinant Der p 2 and rDer f 2 have potential to replace native allergen in diagnostic and therapeutic extracts. Moreover, they can employ as a standard reagent to measure the amount of group 2 allergen in the environment by sandwich-ELISA and utilise this as an immunogen for MAb production.


Provocation proven drug allergy in Thai children with adverse drug reactions
Somying Indradat, Jittima Veskitkul, Punchama Pacharn, Orathai Jirapongsananuruk, Nualanong Visitsunthorn

Background: Adverse drug reactions (ADRs) are a common healthcare problem. The drug provocation test (DPT) is a gold standard for ADR diagnosis.
Objectives: To evaluate a correlation between history of ADRs, skin prick test (SPT), intradermal test (ID) and DPT in Thai children.
Methods: This was a retrospective review of 211 children under 16 years of age who had a history of ADRs and underwent DPT from January 2006 to December 2012.
Results: Two hundred and thirty six (236) DPTs were performed in 211 children with a history of ADRs. The median age at which DPTs were performed was 4 years. Thirty-four children (14.4%) had positive DPT. The positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, likelihood ratio (LR) + and LR- of SPT were 50, 85.7, 6.9, 98.8%, 5.8 and 0.9, respectively. The PPV, NPV, sensitivity, specificity, LR+ and LR- of ID were 33.3, 84.6, 20, 91.7%, 2.4 and 0.9, respectively. Different presentation of symptoms (maculopapular rashes, urticaria, angioedema and anaphylaxis) did not predict SPT, ID and DPT results. Positive human immunodeficiency virus (HIV), but not atopy, was a risk in the present scope of evaluation for drug allergy (odds ratio 11.44, 95% confidence interval 2.60-50.41).
Conclusion: Drug allergy, denoted by positive DPT, was present in 14.4% of Thai children with a history of ADRs. Antibiotics were the most common cause of ADRs. Both SPT and ID had high NPV and specificity but did not predict DPT results. HIV positivity is a risk factor of drug allergy in Thai children.


Risk factors of atopic dermatitis in Korean schoolchildren: 2010 international study of asthma and allergies in childhood
Yong Mean Park, So-Yeon Lee, Woo Kyung Kim, Man Yong Han, Jihyun Kim, Yoomi Chae, Myung-Il Hahm, Kee-Jae Lee, Ho-Jang Kwon, Kang Seo Park, Joon Soo Park, Kangmo Ahn

Background & Objective: We aimed to analyse the risk factors of atopic dermatitis (AD) in Korean schoolchildren in 2010.
Methods: A nationwide, cross-sectional study was conducted in children aged 6-7 years and adolescents aged 12-13 years who were randomly selected. Information was obtained through a Korean version of the International Study of Asthma and Allergies in Childhood questionnaire (ISAAC), and skin prick tests were performed. AD-diagnosed children were selected for risk factor analysis by using logistic regression.
Results: In the univariate logistic regression analysis in 6-7 year-old children, possible risk factors were atopy, a parental history of allergic disease, the use of antibiotics during infancy, a history of having moved into a newly built house during infancy, the presence of visible mould in the house, and remodelling of house within 12 months. The statistical significance persisted after adjustment. However, antibiotic use during infancy and remodelling within 12 months showed no statistical significance as a risk factor for AD. In contrast, multivariate logistic regression analysis in adolescents demonstrated that female sex, atopy, a parental history of allergic diseases, the presence of visible mould in the house, and a history of having moved into a newly built house during infancy was associated with AD. There was no significant association between AD and other risk factors.
Conclusion: In Korean schoolchildren, risk factors such as atopy, the presence of parental allergic diseases, moving into a newly built house during infancy and visible mould in the house were associated with AD.


HAX-1 deficiency: Characteristics of five cases including an asymptomatic patient
Cigdem Aydogmus, Funda Cipe, Melda Tas, Aysenur Akınel, Özlem Öner, Gonca Keskindemirci, Helen Bornaun, Günsel Kutluk, Arzu Babayigit Hocaoglu

Mutation in HAX-1gene cause an autosomal recessive form of Severe congenital neutropenia ( SCN ) and it particularly manifests with recurrent skin, lung and deep tissue infections from the first few months of life.The present study retrospectively evaluated the clinical and laboratory findings of the patients diagnosed with SCN carrying HAX1 gene mutation.
Patients and Results:
A total of five patients, who were diagnosed with SCN carrying HAX1 mutations, were evaluated in terms of clinical and laboratory findings. Of the five patients, three were girls and two were boys, and the mean age of the patients was 8,8 years old (range 4 – 15 years). The mean age of diagnosis was 25.8 months (range 2 months- 5 years). The infections diagnosed included recurrent gingivitis, stomatitis, and skin and soft tissue abscesses. Developmental retardation and epilepsy were present only one patient, whereas speech retardation was present in two patients.All of our patients had HAX-1 mutation, and are still alive and none of them has shown malignant transformation yet.
Complete blood count should be performed and absolute neutrophil count should be evaluated in patients with recurrent severe infections. In the event neutropenia is detected, they should be investigated in terms of SCN and mutation analysis should be performed. This is important both for definite diagnosis of SCN, determination of subtype and treatment planning and also for genetic counseling.
DOI 10.12932/AP0618.34.1.2016


Autophagy machinery impaired interferon signalling pathways to benefit hepatitis B virus replication
Areerat Kunanopparat, Nattiya Hirankarn, Chaivat Kittigu1, Pisit Tangkijvanich, Ingorn Kimkong

Background: Autophagy-related genes ATG4B, ATG7, and ATG12 have been identified to play a critical role in viral replication. However, these genes have yet to be identified in hepatitis B virus (HBV).
Objective: To characterise the role of ATG4B, ATG7, and ATG12 genes in HBV infection.
Methods: The mRNA expression was examined by quantitative real-time RT-PCR and Western blotting. Short hairpin RNA (shRNA) of the target gene was used to examine the function of the gene in HBV replication. Evaluation of HBV DNA level was performed by real-time PCR.
Results: Our findings revealed that ATG12 gene expression was significantly up-regulated (p < 0.005), whereas ATG7 gene expression was down-regulated (p < 0.0001) in HepG2.2.15 cells when compared to HepG2 cells. However, no significant difference in mRNA level of ATG4B was observed. These results were consistent with protein level findings. Moreover, we analysed the function of ATG12 in HBV replication by using ATG12 shRNA and evaluated HBV DNA level. We found that the amount of HBV was decreased in ATG12-knockdown HepG2.2.15 cells when compared to control HepG2.2.15 cells (P <0.05). The mRNA expression of interferon-alpha (IFN-α), interferon-beta (IFN-β), and interferon-inducible genes (IFI) was also investigated. Our results showed that the expression of IFN-α, IFN-β, and IFI27 genes were increased in ATG12-knockdown cells but not in Mx1 gene when compared to control cells (p < 0.005, p < 0.0001 and p <0.005, respectively).
Conclusion: These autophagy-related genes, ATG12 may play a role in HBV replication via impairing IFN pathway. However, the biological significance of other autophagic genes such as ATG7 warrants further study.


Association between flow cytometric crossmatching and graft survival in Thai cadaveric-donor kidney transplantation
Pawinee Kupatawintu, Araya Tatawatorn, Nalinee Premasathian, Yingyos Avihingsanon, Asada Leelahavanichkul, Nattiya Hirankarn

Background: The flow cytometry cross-match (FCXM) technique is a sensitive method and has been reported to predict and protect graft rejection more efficiently than the conventional complement-dependent cytotoxicity cross-match (CDCXM) and the anti-human globulin-complement dependent cytotoxicity (AHG-CDC) methods.
Methods: We performed retrospective FCXM in 270 cadaveric donor kidney transplant patients with negative CDC and AHG. The correlation between FCXM with graft rejection and graft survival within 1 year to 3 years was analysed.
Results: There were 97 (35.9%) samples with positive FCXM. Only 7 (2.6%) of the 270 samples had evidence of antibody-mediated rejection (AMR) at the first year, which increased to 10 (3.7%) AMR samples after 3 years. Interestingly, there was a significant association between FCXM results with the graft outcome at 1 year (P = 0.046). However, when the association was analysed at 3 years after transplantation, it did not reach statistical significance. FCXM detected concordant positive results in 4 out of 8 samples. These samples had mean fluorescence intensity (MFI) of the donor-specific antibody (DSA) higher than 2,000. The DSA was identified by a single antigen bead.
Conclusion: Although positive FCXM, particularly for HLA class I, was significantly associated with graft loss from AMR within 1 year of transplantation in this study, there were a lot of FCXM false positives, as high as 35.9%. Additional studies are required to further assess the usefulness of FCXM in Thailand.


Renin angiotensin system blockers-associated angioedema in the Thai population

Chanita Jangsawang