Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response.

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10+ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1+ but not KLRG1- ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10+ KLRG1+ ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10+ ILC2s in the disease-modifying effect by allergen immunotherapy.

Orodental health status of patients with inborn errors of immunity.

BACKGROUND: Various orodental problems affect patients with inborn errors of immunity (IEI), but there are limited studies on these issues. AIM: To study orodental status and its confounding factors in patients with IEI. DESIGN: Caries, enamel defects, gingival, and soft tissue conditions were examined. Data on patient characteristics, dental hygiene habits, dental attendance, and household income were collected. Statistical analysis and logistic regression were performed. RESULTS: Forty-five participants with a mean age of 9.20 ± 6.41 years were included. Almost all participants had gingivitis (42 of 45; 93.3%), whereas a small number had periodontitis (five of 45; 11.1%). Calculus was found in 33 (73.3%) and caries in 30 (66.7%). Mucosal ulcers, enamel defects, and candidiasis were observed in 23 of 45 (51.1%), 16 of 43 (37.2%), and six of 43 (14.0%), respectively. Chances of having caries, moderate-to-severe gingivitis, periodontitis, calculus, and ulcers increased with age. Taking antibiotics in the last two months increased the risk of caries by five times. Lower income increased the risk of calculus deposit by nine times. CONCLUSION: Gingivitis, calculus, caries, and mucosal ulcers were the most common orodental findings in patients with IEI. Antibiotics increased the risk of caries, and low-income children had higher calculus accumulation.

Clinical characteristics and immunological status of patients with 22q11.2 deletion syndrome in Northern Thailand.

BACKGROUND: 22q11.2 deletion syndrome is one of the most prevalent microdeletion syndromes in humans. The syndrome is characterized by extensive phenotypic variability. OBJECTIVE: to investigate the clinical characteristics, immunological features, and intellectual status of 22q11.2 deletion syndrome patients at Chiang Mai University Hospital, Thailand. METHODS: Patients who had a confirmed diagnosis of 22q11.2 deletion syndrome by fluorescent in situ hybridization (FISH) were enrolled. Data collated and evaluated included that pertaining to history, physical examination, laboratory testing including T-cell, immunoglobulin, calcium, thyroid and parathyroid levels in the blood, cardiac and urological imaging, and intellectual status. RESULTS: 34 patients diagnosed with 22q11.2 deletion syndrome; 18 (53%) were female. The median age of patients was 18.5 months (IQR; 1.5-35.8). Ninety-one percent of patients had characteristic facial features; 94% had a congenital heart defect with tetralogy of Fallot being the most frequent (72%); 88% had hypocalcemia, and 35% had genitourinary tract abnormalities. Recurrence of 22q11.2 deletion syndrome in the family was detected in 18% of cases. Twenty-eight patients (82%) were found to have a low number or percentage of T-cells. Five patients (15%) had low immunoglobulin levels. Intellectual disability (IQ/DQ scores < 70) were found in 20 out of 25 patients who were evaluated (80%), whereas the other five (20%) performed at a level of borderline intellectual function. CONCLUSIONS: Tetralogy of Fallot, hypocalcemia, immunologic defect, and cognitive impairment were common in our 22q11.2 deletion syndrome study group. We recommend that all affected patients have a multi-system evaluation by a comprehensive care team.

Practical recommendations for home-nebulized corticosteroid use in children aged ≤ 5 years with asthma: A review and advisory group consensus.

BACKGROUND: Despite nebulized budesonide being identified by the Global Initiative for Asthma report as a viable alternative to inhaled corticosteroids (ICS) delivered by pressurized metered-dose inhalers (pMDIs) with spacers, practical guidance on nebulized corticosteroid use in the pediatric population remains scarce. OBJECTIVE: To review the current literature and provide practical recommendations for nebulized budesonide use in children aged ≤ 5 years with a diagnosis of asthma. METHODS: A group of 15 expert pediatricians in the respiratory and allergy fields in Thailand developed Delphi consensus recommendations on nebulized budesonide use based on their clinical expertise and a review of the published literature. Studies that evaluated the efficacy (effectiveness) and/or safety of nebulized budesonide in children aged ≤ 5 years with asthma were assessed. AR patients. RESULTS: Overall, 24 clinical studies published between 1993 and 2020 met the inclusion criteria for review. Overall, results demonstrated that nebulized budesonide significantly improved symptom control and reduced exacerbations, asthma-related hospitalizations, and the requirement for oral corticosteroids compared with placebo or active controls. Nebulized budesonide was well tolerated, with no severe or drug-related adverse events reported. Following a review of the published evidence and group consensus, a treatment algorithm as per the Thai Pediatric Asthma 2020 Guidelines was proposed, based on the availability of medications in Thailand, to include nebulized budesonide as the initial treatment option alongside ICS delivered by pMDIs with spacers in children aged ≤ 5 years. CONCLUSIONS: ThNebulized budesonide is an effective and well-tolerated treatment option in children aged ≤ 5 years with asthma.

Allergen immunotherapy for respiratory allergies in clinical practice: A comprehensive review.

Allergen-specific immunotherapy (AIT) is the only treatment that modifies the underlying pathophysiology of IgE-mediated allergic diseases. Evidence shows the efficacy in achieving better control of the symptoms and reduction in medication use in patients with allergic rhinoconjunctivitis and/or asthma. It should be used in association with proper pharmacotherapy for at least three years. The benefits are sustained for several years after discontinuation of treatment. Moreover, it may prevent the development of new sensitization and progression of disease from allergic rhinitis to asthma in children. The favorable efficacy of AIT is associate to the appropriate selection of patients, allergen extracts, adherence, and duration of treatment. Safety during AIT is another concerning issue. AIT has an acceptable safety profile if administered under the appropriate circumstances. Future studies investigating the prescription, efficacy, and safety need to be developed. The new application routes, use of adjuvants, modification of allergens, and use of biologics are currently under evaluation. Moreover, there is an urgent need for real-world data in developing countries regarding the cost-effectiveness analysis, and optimization of AIT schedules and products, so that clinical practice and implementation of AIT for respiratory allergic diseases can be effective and safe.

House dust mite allergen immunotherapy for monosensitized versus polysensitized patients with allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: Most patients with allergic rhinitis are polysensitized. The efficacy of house dust mite (HDM) allergen immunotherapy (AIT) compared between monosensitized and polysensitized patients remains limited. OBJECTIVE: To systematically review the efficacy and safety of HDM AIT compared between monosensitized and polysensitized patients with allergic rhinitis. METHODS: We searched PubMed/MEDLINE, Scopus, EMBASE, and the Cochrane central register of Controlled Trials (CENTRAL) until June 2022. The primary outcome was the changes from baseline in total nasal symptom score (TNSS). Secondary outcomes were changes from baseline in total medication score (TMS), combined symptom medication score (CSMS), visual analog scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, immunological parameters, and adverse events (AEs). RESULTS: Of 13 eligible studies, 10 prospective cohorts, 2 retrospective cohorts, and 1 matched cohort, we identified 10 studies for quantitative synthesis. There were 1,113 patients with allergic rhinitis, 566 with HDM monosensitization and 547 with polysensitization to HDM and other allergens. There was no significant difference in the pooled mean changes of the 2 groups in TNSS (SMD -0.05, 95%CI: -0.22 to 0.11, p = 0.532) and VAS (SMD -0.20, 95%CI: -0.42 to 0.01, p = 0.060) with moderate certainty of evidence. The changes in TMS, CSMS, and RQLQ were similar between the 2 groups with very low certainty of evidence. The AEs were mild and comparable between the 2 groups. The immunological indices remained inconsistent and were not predictive of clinical responses. CONCLUSIONS: A single HDM AIT similarly improved clinical outcomes in monosensitized and polysensitized patients with allergic rhinitis.

Clinical and immunological characteristics of bee venom hypersensitivity among beekeepers in Thailand.

BACKGROUND: Bee venom (BV) hypersensitivity can be severe and potentially life-threatening. Beekeepers heavily exposed to bee stings and are thus at a high-risk group. The data on bee sting reactions among beekeepers in Thailand is limited. OBJECTIVE: To determine the prevalence, clinical and immunological characteristics, and the knowledge of BV hypersensitivity in Thai beekeepers. METHODS: A self-reported questionnaire survey about BV reactions in beekeepers were conducted. Further blood test for immunological parameters: serum BV-specific IgE (BV sIgE), phospholipase A2-specific IgE (Api m1 sIgE), and BV-specific IgG4 (BV sIgG4) were compared between non-allergic beekeepers, patients with a history of bee sting anaphylaxis and the non-allergic control group. RESULTS: A total of 202 out of 447 questionnaires (response rate 45%) were returned. The median age was 46.7 years. Systemic reactions were documented in 6.4%. Younger than 45 years was found to be a factor associated with systemic reactions (OR, 4.35; 95% CI, 1.16-16.31). The BV sIgE and Api m1 sIgE were significantly higher in the anaphylaxis group (p = 0.001). The median of BV sIgG4 was significantly higher in non-allergic beekeepers (p = 0.001). For the knowledge of BV hypersensitivity, 56.4% recognized that BV hypersensitivity could be fatal but only 6% knew about epinephrine auto-injector device. CONCLUSIONS: The prevalence of systemic reactions after stings among Thai beekeepers was not high, which might be due to the tolerance induced by natural exposure via sIgG4. The level of knowledge of BV hypersensitivity among beekeepers was insufficient, more education must be provided.

Anaphylaxis: Ten-year retrospective study from a tertiary-care hospital in Asia.

BACKGROUND: The study of anaphylaxis in different geographic areas raises the awareness to improve prevention and medical care. OBJECTIVE: To investigate the incidence, causes, characteristics, and management of anaphylaxis in Chiang Mai, Thailand. METHODS: We performed a retrospective review, based on ICD-10 electronic medical records of patients who attended the Out-Patient and Emergency Departments at Chiang Mai University Hospital from January 2007 to December 2016. RESULTS: A total of 441 episodes of anaphylaxis in 433 patients were analyzed. Three-hundred and sixty-two (84%) were adults and 71 (16%) were children. Anaphylaxis was common in the second and third decades of life. The incidence rate for all causes of anaphylaxis was 3.9 episodes per 100,000 out-patient and emergency visits per year. The rate in children was more frequent than in adults. Foods were the most common culprit (47%), followed by insect stings (23%) and drugs (18%). Severe anaphylaxis, defined as the loss of consciousness, hypotension, respiratory failure, or cyanosis were found in 163 events (37%). The time lapses between exposure with an allergen and the onset of symptom less than 30 minutes and triggered by insect stings were significantly associated with severe anaphylaxis. Biphasic reactions occurred in 6 patients (1.4%). Adrenaline injections were prescribed in most of patients (90%). There were no fatality cases in the past 10 years. CONCLUSIONS: The incidence of anaphylaxis in our hospital appears more often in children than in adults. The frequency in adults trends to be increasing. Food and insect stings are the common causative agents.

Bee Sting Injuries in Thailand's High Apicultural Area: Outcome, Risk and Treatment Patterns.

Objective: This study aims to assess the clinical outcomes and risk factors associated with severe systemic reactions following bee stings, focusing on patients treated at Pa-Sang Community Hospital, located in Lamphun Province, Thailand, which is recognized as one of the country's largest apicultural areas. Methods: A retrospective review was conducted, utilizing electronic medical records with ICD-10 coding, of patients treated for bee sting injuries at the Emergency Department of Pa-Sang Hospital from January 2015 to December 2019. Results: This analysis included a total of 591 bee sting events involving 533 patients. The average incidence of bee sting injuries was 31.3 per 10,000 Emergency Department visits, with 55% being male. A significant majority (86%) of events occurred outside the patients' home area. Notably, the head or extremities (49%) were the most common anatomical sites stung. Systemic reactions were observed in 44% of cases, with 96 visits (16%) diagnosed as anaphylaxis. Epinephrine injection was administered in 77% of these cases, and fortunately, no fatal anaphylactic reactions were recorded. Protective factors for anaphylaxis and severe systemic reactions after bee stings included age less than 15 years old and stings on extremities. Conversely, having more than ten bee stings and seeking Emergency Department treatment within 60 minutes of being stung were identified as significant risk factors. Conclusion: Bee sting injuries were a common presentation at the hospital situated in the high apicultural area, and severe systemic reactions were observed. This study highlights the need for comprehensive interventions to mitigate the increased risk of bee-related accidents in communities with thriving apicultural industries.

Impact of Air Pollution and Allergic Status on Health-Related Quality of Life among University Students in Northern Thailand.

BACKGROUND: Global awareness of ambient air pollution has heightened due to its detrimental impact on health, particularly in regions with elevated PM2.5 levels. Chiang Mai has emerged as an area experiencing the highest PM2.5 levels in Thailand. OBJECTIVES: to examine the prevalence of respiratory allergies and assess the impact of air pollution on the health-related quality of life (QoL) among university students in Chiang Mai. METHODS: Chiang Mai University (CMU) and Maejo University (MJU) students were recruited. The Global Asthma Network (GAN) questionnaire screened for respiratory allergies (RAs). The disease-specific QoL questionnaire (Rcq-36) was administered twice during low-PM2.5 and high-PM2.5 seasons to evaluate air pollution's impact on health-related QoL. Those showing potential RAs underwent a skin prick test (SPT) to investigate allergic sensitization. RESULTS: Out of 406 participants, 131 (32%) reported respiratory allergies. Among those undergoing SPT, a high rate (82.54%) had positive results. Across both universities, students reported significantly lower QoL in multiple domains, particularly respiratory, eye, sleep, and emotional well-being, during the high-PM2.5 season. This aligned with their poorer self-reported health on a visual analog scale (VAS; p-value < 0.01). PM2.5 levels significantly impacted social functioning for CMU students (p-value = 0.001) and role limitations for MJU students (p-value < 0.001). Notably, participants without respiratory allergies (non-RAs) were more significantly affected by PM2.5 than RA participants in almost all parameters, despite experiencing fewer baseline symptoms. CONCLUSIONS: Respiratory allergies, particularly allergic rhinitis, are prevalent among university students in Chiang Mai. This study underscores the substantial negative impact of ambient air pollution on QoL for both allergic and non-allergic students.

Trehalose phosphorylase as a novel potential allergen in a case of allergic reaction due to oyster mushroom (Pleurotus ostreatus) ingestion.

To our knowledge, we present the first case report of allergic reaction from oyster mushroom ingestion, which was confirmed by an oral food challenge test. Trehalose phosphorylase was identified as a novel potential allergen by IgE immunoblotting and mass spectrometry.

Genetic association of beta-lactams-induced hypersensitivity reactions: A systematic review of genome-wide evidence and meta-analysis of candidate genes.

Importance: Beta-lactams (BLs) are the most prescribed antibiotics, being the most frequent cause of drug allergy. However, the association between BL allergy and genetic variations is still unclear. Objective: This systematic review and meta-analysis aimed to summarize the genetic effects of BL-induced hypersensitivity using existing evidence. Methods: We searched PubMed, Medline, Scopus, EMBASE, CINAHL, and Cochrane Library from inception to September 15, 2022 with no language restriction. Genetic association studies investigating genetic variant/polymorphism and risk of drug-induced hypersensitivity reactions among individuals receiving BL-antibiotics were included. We excluded studies of acute interstitial nephritis, drug-induced liver injury, serum sickness, and isolated drug fever. Data were comprehensively synthesized and quality of study were assessed using STrengthening the Reporting of Genetic Association Studies (STREGA). The record screening, extraction and quality assessment were performed by two reviewers and discussions were made to resolve discrepancies. The effects of each variant were pooled and evaluated by modified Venice criteria. Results: A total of 9276 records were identified, and 31 studies were eligible for inclusion. Twenty-seven were candidate-gene association studies (5416 cases and 5939 controls), while the others were next-generation sequencing (NGS) or genome-wide association studies (GWASs) (119 838 cases and 1 487 111 controls). Forty-nine polymorphisms were identified and most of them located in allergic reaction pathways. Meta-analyses of 15 candidate variants in a mixture of both immediate and non-immediate reactions revealed weak genetic effects of rs1801275 (8 studies; n = 1,560; odd ratio 0.73; 95%CI: 0.57-0.93) and rs20541 (4 studies; n = 1,482; odd ratio 1.34; 95%CI: 1.07-1.68) in IL4R and IL13, respectively. Results from GWASs and NGS identified, and confirmed associations in HLA regions including HLA-DRA, HLA-B, HLA-DQA, HLA-DRB1, and HLA-DRB3. Conclusion: Our study summarized genetic evidence influencing BL-induced hypersensitivity and estimated effects of potential variants. We postulated that the genomic studies provide better insights to the mechanism of reactions and suggest potential effects of HLA Class II variants. However, results were inconsistent and unable to generalize in different settings. Further high-throughput studies with a well-defined function, epigenetic interaction, incorporated with clinical factors, would be beneficial for risk identification in BL-induced hypersensitivity.

Prevalence of food allergy among preschool children in northern Thailand.

BACKGROUND: The epidemiology and clinical spectrum of food allergies (FA) confirmed by oral food challenge tests (OFC) in the Southeast Asian countries are limited. The aim of the present study was to examine the prevalence and characteristics of FA among preschool children in northern Thailand. METHODS: Five hundred and forty-six children aged 3-7 years living in Chiang Mai, Thailand participated in this study. A cross-sectional parent questionnaire survey was conducted. Families with children reporting FA were invited to undergo further investigations with skin prick testing, serum specific IgE, and OFC. RESULTS: A total of 452 out of 546 questionnaires (82.8%) were returned. Forty-two children (9.3%) were reported to have FA. The five leading allergic foods reported were shrimp, cow's milk, fish, chicken eggs, and ant eggs. The most commonly reported symptom was a skin rash (78.0%), followed by abdominal pain and vomiting (31.1%). Anaphylaxis was found in two children (3.4%), from ant eggs allergy. Eighteen children underwent OFC; five of them were positive to shrimp, fish, and crab. Either skin prick test or serum-specific IgE was positive in these children. Factors associated with parent-reported FA included personal and family history of atopic dermatitis. CONCLUSIONS: The prevalence of IgE-mediated FA confirmed on OFC was ≥ 1.11% (95% confidence interval: 0.41-2.98%). The most common causative food was shrimp. Ant eggs were a unique food allergen causing severe reactions in preschool children in northern Thailand.

Efficacy and safety of house dust mite sublingual immunotherapy tablets in allergic rhinitis: A systematic review and meta-analysis.

Background: House dust mite (HDM) sublingual immunotherapy (SLIT) tablets have been approved for the treatment of patients with allergic rhinitis (AR). However, the meta-analysis on the efficacy of HDM-SLIT tablets for HDM-induced AR patients remained limited. Methods: Five databases were searched including: PubMed/MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and CINAHL for randomized controlled trials (RCTs) that addressed the efficacy and safetyof HDM-SLIT tablets compared with placebo until January 2022. The primary outcome was a combined symptom and medication score (CSMS) after treatment. Results: Eight eligible RCTs were identified with a total of 3601 patients treated with HDM-SLIT tablets and 2783 patients who received a placebo. The CSMS was significantly lower in the HDM-SLIT tablet group compared with the placebo (standardized mean difference (SMD) -0.28 [95% CI: -0.32 to -0.23]). There was a significant reduction in rhinitis symptom scores, rhinitis medication scores, total combined conjunctivitis scores, and rhinoconjunctivitis quality of life questionnaire scores. The consistent efficacy compared to the placebo has been exhibited over the different kinds and doses of HDM tablets (6 SQ, 12 SQ, 300 IR, and 500 IR) and age groups (>5 years old, adolescents and adults) with low degrees of variability across the studies. There was no significant difference in proportions of participants who were injected with epinephrine between the treatment- and placebo groups. Conclusions: HDM-SLIT tablet is an effective treatment in reducing rhinitis symptoms and medication use in AR patients with favorable safety. They also improve quality of life and conjunctivitis symptoms.

Genetic Association of Beta-Lactams-Induced Hypersensitivity Reactions: A Protocol for Systematic Review and Meta-Analysis.

Beta-lactam (BL) antibiotics are among the drugs commonly related to hypersensitivity reactions. Several candidate gene studies and genome-wide association studies have reported associations of genetic variants and hypersensitivity reactions induced by BL antibiotics. However, the results were inconclusive. This protocol details a comprehensive systematic review of genetic factors associated with BL-induced hypersensitivity. A systematic search of literature related to genetic associations of BL-induced hypersensitivity will be performed through PubMed, Medline, Scopus, EMBASE, Web of Science, CINAHL, and the Cochrane central register of Controlled Trials (CENTRAL) from their inception dates with no language restrictions. Two reviewers will independently screen, extract, and appraise the risk of bias. Frequencies of genetic variants that comply with Hardy-Weinberg equilibrium will be extracted and pooled. Genetic models will be applied to variant effect calculation as per allele and genotype analysis. Based on statistical heterogeneity among studies, common effect estimation (odds ratio) and its corresponding 95% confidence interval will be analyzed. Sensitivity and subgroup analyses will be performed to determine the robustness of eligible studies. This systematic review and meta-analysis will provide comprehensive evidence of genetic effects regarding BL-induced hypersensitivity. The findings will enlighten the determination of disease-related genotypes that would potentially reveal allergy profiling in patients.

The prevalence and temporal trends of food allergy among preschool children in Northern Thailand between 2010 and 2019.

BACKGROUND: Although recent studies suggest that the prevalence of food allergy (FA) has not changed, the data from developing countries are limited. This study aimed to investigate time trends in the prevalence of FA among preschool children in 2010 and 2019 in Northern Thailand. METHODS: Two cross-sectional studies were performed, 9 years apart (2010 and 2019), using the same methods, in children aged 3-7 years living in Chiang Mai, Thailand. Parent-reporting questionnaire surveys were conducted. Families with children reporting FA were invited to undergo further investigations with skin prick testing, serum specific IgE, and oral food challenge (OFC). The prevalence of parent-reported FA, food sensitization, and OFC-confirmed FA were compared between the 2 periods. RESULTS: A total of 1013 out of 1146 questionnaires (452/546 in 2010 and 561/600 in 2019) were returned. The response rate was 88.4%. The prevalence of parent-reported food allergy in 2019 was significantly lower than that in 2010 (5.5% vs 9.3%; p = 0.02). However, there was no significant change in the prevalence of OFC-confirmed FA (0.9% vs 1.1%; p = 0.75). Three leading causative foods of parent-reported FA were cow's milk, shrimp, and eggs. Shrimp was still the most common OFC-confirmed food allergen. Atopic dermatitis was the most significantly parent reported factor associated with FA. CONCLUSION: The overall prevalence of FA among preschool children in Northern Thailand had not increased during the past decade. There was no significant difference in the prevalence of OFC-confirmed FA between 2010 and 2019.

Allergic Rhinitis: What Do We Know About Allergen-Specific Immunotherapy?

Allergic rhinitis (AR) is an IgE-mediated disease that is characterized by Th2 joint inflammation. Allergen-specific immunotherapy (AIT) is indicated for AR when symptoms remain uncontrolled despite medication and allergen avoidance. AIT is considered to have been effective if it alleviated allergic symptoms, decreased medication use, improved the quality of life even after treatment cessation, and prevented the progression of AR to asthma and the onset of new sensitization. AIT can be administered subcutaneously or sublingually, and novel routes are still being developed, such as intra-lymphatically and epicutaneously. AIT aims at inducing allergen tolerance through modification of innate and adaptive immunologic responses. The main mechanism of AIT is control of type 2 inflammatory cells through induction of various functional regulatory cells such as regulatory T cells (Tregs), follicular T cells (Tfr), B cells (Bregs), dendritic cells (DCregs), innate lymphoid cells (IL-10+ ILCs), and natural killer cells (NKregs). However, AIT has a number of disadvantages: the long treatment period required to achieve greater efficacy, high cost, systemic allergic reactions, and the absence of a biomarker for predicting treatment responders. Currently, adjunctive therapies, vaccine adjuvants, and novel vaccine technologies are being studied to overcome the problems associated with AIT. This review presents an updated overview of AIT, with a special focus on AR.

Application of Flow Cytometry in the Diagnostics Pipeline of Primary Immunodeficiencies Underlying Disseminated Talaromyces marneffei Infection in HIV-Negative Children.

Talaromyces (Penicillium) marneffei is an AIDS-defining infection in Southeast Asia and is associated with high mortality. It is rare in non-immunosuppressed individuals, especially children. Little is known about host immune response and genetic susceptibility to this endemic fungus. Genetic defects in the interferon-gamma (IFN-γ)/STAT1 signaling pathway, CD40/CD40 ligand- and IL12/IL12-receptor-mediated crosstalk between phagocytes and T-cells, and STAT3-mediated Th17 differentiation have been reported in HIV-negative children with talaromycosis and other endemic mycoses such as histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis. There is a need to design a diagnostic algorithm to evaluate such patients. In this article, we review a cohort of pediatric patients with disseminated talaromycosis referred to the Asian Primary Immunodeficiency Network for genetic diagnosis of PID. Using these illustrative cases, we propose a diagnostics pipeline that begins with immunoglobulin pattern (IgG, IgA, IgM, and IgE) and enumeration of lymphocyte subpopulations (T-, B-, and NK-cells). The former could provide clues for hyper-IgM syndrome and hyper-IgE syndrome. Flow cytometric evaluation of CD40L expression should be performed for patients suspected to have X-linked hyper-IgM syndrome. Defects in interferon-mediated JAK-STAT signaling are evaluated by STAT1 phosphorylation studies by flow cytometry. STAT1 hyperphosphorylation in response to IFN-α or IFN-γ and delayed dephosphorylation is diagnostic for gain-of-function STAT1 disorder, while absent STAT1 phosphorylation in response to IFN-γ but normal response to IFN-α is suggestive of IFN-γ receptor deficiency. This simple and rapid diagnostic algorithm will be useful in guiding genetic studies for patients with disseminated talaromycosis requiring immunological investigations.

Hypoalbuminaemia at admission predicts the poor outcomes in critically ill children.

BACKGROUND: Hypoalbuminaemia at admission is a common finding in patients admitted to the Paediatric Intensive Care Unit (PICU) and it is thought that this may predict morbidity and mortality. METHODS: A retrospective study was conducted in the tertiary hospital. The medical records of critically ill children were reviewed. The data were analyzed for the prevalence of hypoalbuminaemia and outcomes. RESULTS: Two hundred and two patients were included in the analysis. The incidence of hypoalbuminaemia at admission was 57.9%. These patients had a mortality rate 4 times greater (adjusted odds ratio 3.8; 95% CI: 1.4-10.0), a longer length of PICU stay (8.6 vs. 6.7 days, P = 0.04) and a longer period on a ventilator (5.9 vs. 3.9 days, P = 0.04) than patients with normal albumin levels. CONCLUSIONS: Hypoalbuminaemia at admission was a predictive factor of poor outcome in critically ill children. It is associated with a higher mortality, a longer length of stay in the PICU, as well as longer ventilator use.