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PURPOSE: Vitamin D (VitD) is an immunomodulatory molecule capable of alleviating allergic symptoms. However, the effectiveness of allergen-specific immunotherapy (AIT) is not commonly evidenced in the early build-up phase. The aim of the study was to determine the potential of VitD supplementation in this treatment phase. METHODS: Thirty-four house dust mite (HDM)-allergic adult patients treated with subcutaneous AIT were randomized to receive VitD2 60,000 IU/week or placebo for 10 weeks and followed up for 10 weeks. The primary endpoints were the symptom-medication score (SMS) and the treatment response rate. The secondary endpoints were eosinophil count and levels of plasma IL-10, Der p 2-specific IgG4, and dysfunctional regulatory T (CRTH2+ Treg) cells. RESULTS: Of 34 patients, 15 in each group completed the study. Patients with VitD deficiency receiving a VitD supplement showed significantly lower mean change SMS than the placebo group in weeks 10 (mean difference -54.54%, P = 0.007) and 20 (mean difference -42.69%, P = 0.04). The percentage of treatment responders reached 78% and 50% in the VitD and placebo groups, respectively, and the effect remained in week 20 (89% and 60%). No significant difference was observed for the tested immunological read-outs, with the exception of the frequency of CRTH2+ Treg cells, which was remarkably reduced in the VitD-treated patients. Moreover, improvement in SMS was correlated to the number of CRTH2+ Treg cells. Our in vitro experiment indicated that VitD downregulated activation markers, whereas it improved the function of CRTH2+ Treg cells. CONCLUSIONS: VitD supplementation in the build-up phase of AIT could relieve symptoms and decrease Treg cell dysfunction, especially in patients with VitD deficiency.

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BACKGROUND: Most of the asthma susceptibility genes have demonstrated moderate effect. Gene-gene interaction may play a role in asthma. OBJECTIVE: To investigate the genetic and gene-gene interaction effects of single nucleotide polymorphisms (SNPs) in the ADAM33, TGFß1, VEGFA, and PLAUR genes on asthma in Thai population. METHODS: Two hundred and fifty control and 250 asthmatic Thai subjects were recruited. Asthma was diagnosed based on symptoms and spirometry assessments using criteria outlined by the American Thoracic Society. Degrees of asthma severity were determined according to guidelines provided by the Global Initiative for Asthma. Asthmatic subjects were subcategorized into the low-severity (n = 106) and high-severity (n = 144) groups. Eleven SNPs in four genes were genotyped, including ADAM33 SNPs (rs528557/S2, rs598418, rs44707/ST+4), TGFß1 SNPs (rs2241715, rs11466345), VEGFA SNPs (rs833069, rs3025010), and PLAUR SNPs (rs344781, rs344787, rs2239374, rs2239372). Association analyses between SNPs and asthma, and tests for gene-gene interaction were performed. RESULTS: The ADAM33 rs528557/S2 SNP was found to be associated with asthma according to the additive and dominant models. Comparison between the low-severity group and controls showed the VEGFA rs833069 SNP to be significantly associated with the low-severity group. No gene-gene interactions were observed in this study. CONCLUSIONS: The ADAM33 rs528557/S2 and the VEGFA rs833069 SNPs were associated with Thai asthmatics, as well as with other populations worldwide. Further studies are warranted to investigate the use these SNPs as biomarkers for establishing early diagnosis or for predicting future risk of asthma.

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BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Allergen-specific immunotherapy is a treatment option for selected patients with severe AD sensitization to house dust mites (HDM). OBJECTIVE: To report the first case of successful treatment with HDM sublingual immunotherapy (SLIT) tablets in patients with severe AD. METHODS: A Thai male patient with HDM sensitization and severe AD who had not responded to topical corticosteroids and calcineurin inhibitors underwent 1 month of HDM subcutaneous immunotherapy (SCIT), after which his skin symptoms were minimally improved. He lost follow-up SCIT and the symptoms worsened, with large wheal lesions appearing at the SCIT injection site, so we decided to switch from SCIT to HDM SLIT tablets. RESULTS: After the SLIT treatment, the AD and skin lesions improved and the medication could be stopped. CONCLUSIONS: HDM SLIT might be an alternative treatment in patients with HDM sensitization and severe AD who are refractory to conventional treatment.

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BACKGROUND: Long-term follow-up of allergen-specific B cells in terms of immunoglobulin isotype expression, plasmablast differentiation, and regulatory B (Breg) cell development during allergen-specific immunotherapy (AIT) has not been reported. OBJECTIVE: Allergen-specific B-cell responses during 2 years of house dust mite AIT were compared between responder and nonresponder patients. METHODS: B cells specific for Der p 1 were detected by using the fluorochrome-labeled allergen method. The frequency of IgA-, IgG1- and IgG4-switched Der p 1-specific B cells, plasmablasts, and IL-10- and IL-1 receptor antagonist (IL-1RA)-producing Breg cells were investigated and correlated to clinical response to AIT. RESULTS: Sixteen of 25 patients completed the 2-year study. Eleven responder patients showed a successful response to AIT, as measured by a decrease in symptom-medication scores from 13.23 ± 0.28 to 2.45 ± 0.24 (P = .001) and a decrease in skin prick test reactivity to house dust mite from 7.0 ± 1.3 to 2.7 ± 0.5 mm (P = .001). IgG4+ and IgA+ Der p 1-specific B cells showed a significant increase after AIT, with a significantly greater frequency in responders compared with nonresponders in the IgG4+ but not the IgA+ fraction. The frequency of plasmablasts and IL-10- and/or IL-1RA-producing Breg cells was greater among responders compared with nonresponders after 2 years. The increased frequency of Der p 1-specific IgG4+ B cells, plasmablasts, and IL-10+ and dual-positive IL-10+IL-1RA+ Breg cells significantly correlated with improved clinical symptoms over the course of AIT. CONCLUSION: Allergen-specific B cells in patients responding to AIT are characterized by increased numbers of IgA- and IgG4-expressing Der p 1-specific B cells, plasmablasts, and IL-10+ and/or IL-1RA+ Breg cells.

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BACKGROUND: Allergen-specific immunotherapy (AIT) is the only available treatment for allergic diseases that can induce specific immune tolerance to allergens. The key mechanisms involved in this process include changes in allergen-specific regulatory T (Treg) cells. METHODS: We studied 25 allergic rhinitis patients undergoing subcutaneous house dust mite-specific immunotherapy. Peripheral blood mononuclear cells were studied before and after 10, 30 weeks, and 3 years of AIT. Der p 1-specific T regulatory cell responses were investigated by characterization of Der p 1-MHC class II tetramer-positive cells and correlated with nasal symptom score. RESULTS: Twelve of 25 AIT patients matched with their MHC class II expression to the Der p 1 peptide-MHC class II tetramers. A significant increase in the numbers of Der p 1-specific FOXP3+ Helios+ CD25+ CD127- Treg cells after 30 weeks was observed, which slightly decreased after 3 years of AIT. In contrast, Der p 1-specific immunoglobulin-like transcript 3 (ILT3)+ CD25+ Treg cells decreased substantially from baseline after 3 years of AIT. ILT3+ Treg cells displayed compromised suppressive function and low FOXP3 expression. In addition, Der p 1-specific IL-10 and IL-22 responses have increased after 30 weeks, but only IL-10+ Der p 1-specific Treg cells remained present at high frequency after 3 years of AIT. Increased number of FOXP3+ Helios+ and IL-10+ and decreased ILT3+ Treg cell responses correlated with improved allergic symptoms. CONCLUSION: The results indicate that AIT involves upregulation of the activated allergen-specific Treg cells and downregulation of dysfunctional allergen-specific Treg cell subset. Correction of dysregulated Treg cells responses during AIT is associated with improved clinical response.

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PURPOSE: Group 2 innate lymphoid cells (ILC2s) have been implicated in the pathogenesis of allergic disease. However, the effect of allergen-specific immunotherapy (AIT) on ILCs remains to be clarified. The aim of this study was to evaluate the levels of ILC subsets in allergic rhinitis (AR) patients in response to house dust mite (HDM)-specific immunotherapy. METHODS: We enrolled 37 AR patients undergoing AIT (16 responders and 11 non-responders) for 2 years, 35 HDM AR patients and 28 healthy subjects. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry to identify ILC subsets. Stimulation of ILC2s with recombinant allergen-specific protein was used to determine ILC2's activation (CD69 expression). RESULTS: Responder AIT patients and healthy subjects had a decreased frequency of circulating ILC2s compared to non-responder AIT and AR patients. Conversely, ILC1s from responder AIT patients and healthy subjects showed increased frequency compared to non-responder AIT and AR patients. The frequency of ILC3s natural cytotoxicity receptor (NCR)⁺ and NCR⁻ in responder AIT patients was significantly lower compared to AR patients and healthy subjects. The ILC1: ILC2 proportion in responder AIT patients was similar to that of healthy subjects. PBMCs from patients who were responders to AIT had a significantly lower expression of the activation marker CD69 on ILC2s in response to allergen re-stimulation compared to AR patients, but no difference compared to non-responder AIT patients and healthy subjects. CONCLUSIONS: We propose that AIT might affect ILC responses. The activation of ILC2s was reduced in AR patients treated with AIT. Our results indicate that a relative ILC1/ILC2 skewed response is a possible key to successful AIT.

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Introduction. Vitamin D deficiency has been linked to an increased risk of asthma exacerbations. Objective. This study aimed to compare vitamin D status during the period of severe asthma exacerbations and investigate if vitamin D supplementation improves asthma control. Methods. A total of 47 asthmatic patients and 40 healthy subjects participated in this study. Serum 25-hydroxyvitamin D (25(OH)D), asthma control test (ACT) score, and % predicted peak expiratory flow rate were evaluated in the period with and without severe asthma exacerbations. After that, we provided vitamin D2 supplements to the patients with low vitamin D levels for 3 months. Results. At the period of asthma exacerbation, the prevalence of vitamin D deficiency and insufficiency was 38.29% and 34.04%. There was no significant difference in the levels of serum 25(OH)D with and without asthma exacerbations but the levels were significantly higher in the healthy group. Serum 25(OH)D levels significantly correlated with ACT score. Moreover, vitamin D2 supplementation improved asthma control in uncontrolled asthma group. Conclusions. Hypovitaminosis D was common in asthmatic patients but was not the leading cause of asthma exacerbations. Serum 25(OH)D levels correlated with the ability to control asthma. Improving vitamin D status might be a benefit in uncontrolled asthmatic patients.

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BACKGROUND: Autologous serum skin test (ASST) and autologous plasma skin test (APST) are simple methods to diagnose autoimmune chronic urticaria. However, the association data of ASST or APST with disease severity and long-term outcome are still unclear. OBJECTIVE: The results of ASST and APST might be used to predict urticaria symptom severity and long-term outcomes among chronic spontaneous urticaria (CSU) patients. METHODS: We evaluated the prevalence of reactive ASST and APST in 128 CSU patients. The patients were characterized by 4 groups: negative, ASST positive, APST positive, and both ASST and APST positive. We observed remission rate among the CSU patients during 2 years. RESULTS: Forty-four of 128 CSU patients (34%) had negative autologous skin test. The CSU patients with positive ASST, positive APST, and both positive ASST and APST were 47 (37%), 6 (5%), and 31 (24%), respectively. No significant difference was found between the groups according to urticaria severity score (USS) and dermatology life quality index (DLQI). Mean wheal diameter of ASST showed positive correlation with DLQI. Also, mean wheal diameter of APST showed positive correlation with USS and DLQI. Both the positive ASST and APST groups had a high proportion of 4-fold dose of H1-antihistamine than the positive ASST (p = 0.03) and negative groups (p = 0.0009). The rate of remission over 2 years in the negative, positive ASST, positive APST, and both positive ASST and APST groups were 81.1%, 62.3%, 60%, and 46.1%, respectively. The urticaria remission rate in patients in the negative group was significantly higher compared with both positive ASST and APST groups (odds ratio, 5.0; 95% confidence interval, 1.61-15.44; p = 0.006). CONCLUSION: ASST and APST results could predict remission rates among patients with CSU. Our results suggested investigating ASST and APST among CSU patients before starting treatment.

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BACKGROUND: The in-depth characterization of the recently identified house dust mite (HDM) major allergen Der p 23 requires the production of its recombinant counterpart because the natural allergen is poorly extractable from fecal pellets. This study aimed to provide a detailed physico-chemical characterization of recombinant Der p 23 (rDer p 23) as well as to investigate its IgE reactivity in a cohort of HDM-allergic patients from Thailand. METHODS: Purified rDer p 23, secreted from recombinant Pichia pastoris, was characterized by mass spectrometry and circular dichroism analyses as well as for its chitin-binding activity. The IgE-binding frequency and allergenicity of Der p 23 were determined by ELISA and RBL-SX38 degranulation assays, respectively. RESULTS: Purified intact rDer p 23 carried O-mannosylation and mainly adopted a random coil structure. Polyclonal antibodies to rDer p 23 can detect the corresponding natural allergen (nDer p 23) in aqueous fecal pellet extracts, suggesting that both forms of Der p 23 share common B-cell epitopes. Despite its homologies with chitin-binding proteins, both natural Der p 23 and rDer p 23 were unable to interact in vitro with chitin matrices. Of 222 Thai HDM-allergic patients tested, 54% displayed Der p 23-specific IgE responses. Finally, the allergenicity of rDer p 23 was confirmed by the degranulation of rat basophil leukemia cells. CONCLUSION: Our findings highlighted important levels of Der p 23 sensitizations in Thailand. Our study clearly suggested that rDer p 23 is likely more appropriate for HDM allergy component-resolved diagnosis than HDM extracts.

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BACKGROUND: Recent findings show food allergy is rarely the cause of chronic urticaria. However; reports showed up to 5% of chronic idiopathic urticaria (CIU) was food induced urticaria (FIU) and the remission rate with food avoidance in CIU was varied. According to recent studies, skin prick test (SPT) is not a gold standard for investigating the culprit food allergen in CIU. The clinical response for food avoidance is still unclear. OBJECTIVE: The purpose of the present study is to investigate the association of food allergen and SP7 the clinical response after positive food avoidance in adult Thai patients with CIU. MATERIAL AND METHOD: We conducted a prospective study that included 76 patients, who presented with CIU at the Division of Dermatology, Department of Medicine, Phramongkutklao Hospital, between September 1, 2009 and May 31, 2010. Personal data, general physical examination, and detailed history were obtained. Twenty food allergens were used to perform SPT at the allergy clinic. The positive food allergens were enrolled to avoid the culprit food allergens for two to four weeks and evaluated the clinical response. RESULTS: Fifty-one of 76 patients (67.1%) gave history compatible with FIU. Shrimp (54.9%) and fish (49.0%) were the two most commonly suspected allergens by the patients. Fifteen of 76 patients (19.7%) had positive SPT In comparison to the SPT negative group in terms of clinical severity and effect on their daily lives, there was no significant difference. We then matched the SPT results with the patient's history. Five of 76 (6.6%) patients had results of SPT matching the patients' history. The five allergens in these patients were fish, milk, tomato, shrimp, and yeast. Fifty-one of 76 (67.1%) patients had negative SPT results but the patients suspected that certain foods were the cause of their urticaria. Fifteen of 76 (19.7%) patients had positive SPT results but the patients had never suspected any food allergen. Among these SPT positive patients, 13 food allergens were the culprits, the first three most common SPT allergens in this group were peanut, oyster and tomato. Upon SPT positive food avoidance, 12 of 15 (80%) SPT+ patients had significant improvement of symptom score in term of clinical severity and effect on their daily lives. CONCLUSION: Although SPT still yielded a low sensitivity for the diagnosis of FIU, the present study showed a very good response by food avoidance in patients who were SPT positive.

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Tracheobronchomalacia (TBM) is defined as the condition where the airway lumen narrows more than 50 percent. The acquired TBM usually occurs in adults; however, the prevalence of TBM in asthma is unknown. We report two cases of severe asthma in elderly patients that could not be controlled with higher medication use. Case 1 was a 70-year-old woman with sever persistent asthma for 10 years, presented with uncontrolled symptoms for 4 months. A CT of the chest showed collapse of the trachea at the posterior wall. Case 2 involved a 72-year-old woman with partly controlled asthma presenting with uncontrolled symptoms for 3 months. A CT of the chest showed normal distal tracheal anteroposterior diameter. However, bronchoscopy showed bronchomalacia at the right and left bronchus of the lower lungs. Patients who have severe asthma, despite adequate treatment with medication, should be further investigated to exclude other diseases that have clinical features similar to asthma such as tracheobronchomalacia, particularly in the elderly.

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Atopic dermatitis (AD) is one of the most common chronic skin diseases. Treatment options include lubricants, antihistamines, and corticosteroids in either topical or oral forms. Severe AD is frequently recalcitrant to these medications. We reported three cases of severe AD patients who had elevated of IgE levels and failed to response to several prior medical treatment. After being treated with Omalizumab (humanized monoclonal anti-IgE antibody), the patients had marked alleviation of symptoms with improved Eczema Area and Severity Index (EASI) and pruritic scores. No patient experienced adverse effect.

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Phuk-waan-ban, Euphorbiaceae Sauropus androgynus (Linn) Merr, belongs to the family Euphorbiaceae, which is the same as the rubber tree, Euphorbiaceae Hevea brasiliensis. The young leaves are edible. To the best of the authors knowledge, this is the first report of anaphylactic reaction to Phuk-waan-ban in latex allergic patients. Contact urticaria and anaphylactic reactions to latex-containing rubber products are being recognized with increasing frequency in all kinds of medical disciplines. The prevalence and incidence are both increasing. Recently, a number of reports have been published describing anaphylactic reactions to food items in patients with latex allergy. The authors present a patient with occupational natural rubber allergy who developed an anaphylactic reaction with urticarial rash 20-30 minutes after ingestion of phuk-waan-ban. The diagnostic work up showed specific IgE to latex (CAP class 3). Positive skin prick tests to latex and cooked and raw phuk-waan-ban crude extract confirmed allergic reactions. Moreover, the cross-reaction between phuk-waan-ban and latex can be confirmed by using IgE inhibition test.

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OBJECTIVE: To determine attitude and knowledge of patients with asthma and allergic rhinitis who received AIT (Allergen Immunotherapy). STUDY DESIGN: A cross-sectional analytical study. MATERIAL AND METHOD: A cross-sectional descriptive study was conducted in the patients with allergic asthma and allergic rhinitis whom were treated with AIT at the Allergy Clinic, Phramongkutklao Hospital between February 1st 2008 to October 31st 2008. Standardized questionnaires were used to collect patients demographic data, attitude and knowledge. RESULTS: A total of 100 patients were enrolled in this study. Sixty-six percents of patients expected that AIT would improve their quality of lifes and could prevent their disease recurrence. Fifty three percents of patients expected that their allergic diseases could be cured completely while 22 percents of patients expected that AIT could prevent the occurrence of a new allergic disease. Only 42 percents of patients understood that AIT would improve the conditions after treatment at least 6 months. Twenty two percent of patients knew that AIT was safe and there was no serious side effect. CONCLUSION: Patients treated with AIT had still lack of knowledge about AIT treatment and the potential serious side effect that could occur.

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ADAM33 (A Disintegrin And Metalloprotease 33) is an asthma susceptibility gene found across several human populations. However, no information on ADAM33 exists for Thai population. The objective of this study was to determine the association, if any, between ADAM33 polymorphisms and asthma in Thai subjects. Genotyping revealed 8 single nucleotide polymorphisms (SNPs) within the 3' region of the ADAM33 gene among 200 asthmatics and 100 control subjects. Asthmatic subjects were further sub-categorized into high and low severity groups. Multiple genetic model statistic tests for single-marker and haplotype association were carried out. Differences in allele frequencies at the SNPs rs528557/S2, rs598418 and rs44707/ST+4 in asthmatics were statistically significant compared to controls. The SNP rs528557/S2 could also be linked to the low severity group and the SNPs rs598418 and rs44707/ST+4 with the high severity group. Two-SNP haplotype analysis at the SNPs rs528557/S2 and rs598418 revealed a significant association with asthma. This study in a Thai population confirmed a positive association between ADAM33 polymorphisms and asthma susceptibility.

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