Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity.

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott-Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.

Evaluation of Stool Short Chain Fatty Acids Profiles in the First Year of Life With Childhood Atopy-Related Outcomes.

Introduction: Short chain fatty acids (SCFAs) are the main intestinal intermediate and end products of metabolism of dietary fibers/polyphenols by the gut microbiota. The aim of this study was to evaluate the biological implication of stool SCFA profiles determined in the first year of life on the clinical presentation of allergic outcomes in childhood. Methods: From the Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort, a sub-cohort of 75 participants was recruited. Scheduled questionnaire data was collected for cumulative prevalence of physician-diagnosed eczema, wheezing with the use of nebuliser, and allergen sensitization till the age of 8 years. Stool samples collected at week 3 and months 3, 6 and 12 were quantitated for 9 SCFAs using LC/MS/MS. SCFA data were grouped into lower (below the 25th) and higher (above the 75th percentiles) categories. Generalized Linear Mixed Models was employed to analyse longitudinal association between SCFAs and atopy-related outcomes. Results: Children with lower stool butyric acid levels (≤25th percentile) over the first 3 time points had higher odds ratio (OR) for wheezing (adjOR = 14.6), eczema (adjOR = 13.2), food sensitization (adjOR = 12.3) and combined outcomes of both wheezing and eczema (adjOR = 22.6) till age 8 years, compared to those with higher levels (≥75 percentile). Additionally, lower longitudinal levels of propionic acid (≤25th percentile) over 4 time points in first year of life was associated with recurrent wheezing (≥2 episodes) till 8 years (adjOR = 7.4) (adj p < 0.05). Conclusion: Our results suggest that relatively low levels of gut SCFAs in early life are associated with increased susceptibility to atopic-related outcomes in childhood.

Phenomic Analysis of Chronic Granulomatous Disease Reveals More Severe Integumentary Infections in X-Linked Compared With Autosomal Recessive Chronic Granulomatous Disease.

Background: Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI), characterised by recurrent bacterial and fungal infections. It is inherited either in an X-linked (XL) or autosomal recessive (AR) mode. Phenome refers to the entire set of phenotypes expressed, and its study allows us to generate new knowledge of the disease. The objective of the study is to reveal the phenomic differences between XL and AR-CGD by using Human Phenotype Ontology (HPO) terms. Methods: We collected data on 117 patients with genetically diagnosed CGD from Asia and Africa referred to the Asian Primary Immunodeficiency Network (APID network). Only 90 patients with sufficient clinical information were included for phenomic analysis. We used HPO terms to describe all phenotypes manifested in the patients. Results: XL-CGD patients had a lower age of onset, referral, clinical diagnosis, and genetic diagnosis compared with AR-CGD patients. The integument and central nervous system were more frequently affected in XL-CGD patients. Regarding HPO terms, perianal abscess, cutaneous abscess, and elevated hepatic transaminase were correlated with XL-CGD. A higher percentage of XL-CGD patients presented with BCGitis/BCGosis as their first manifestation. Among our CGD patients, lung was the most frequently infected organ, with gastrointestinal system and skin ranking second and third, respectively. Aspergillus species, Mycobacterium bovis, and Mycobacteirum tuberculosis were the most frequent pathogens to be found. Conclusion: Phenomic analysis confirmed that XL-CGD patients have more recurrent and aggressive infections compared with AR-CGD patients. Various phenotypic differences listed out can be used as clinical handles to distinguish XL or AR-CGD based on clinical features.

Trajectories of early-onset rhinitis in the Singapore GUSTO mother-offspring cohort.

BACKGROUND: The natural history of childhood rhinitis is not well described. OBJECTIVE: This study aimed to identify different rhinitis trajectories in early childhood and their predictors and allergic associations. METHODS: Rhinitis symptoms were ascertained prospectively from birth until 6 years using standardized questionnaires in 772 participants. Rhinitis was defined as one or more episodes of sneezing, runny and/or blocked nose >2 weeks duration. Latent trajectories were identified using group-based modelling, and their predictive risk factors and allergic associations were examined. RESULTS: Three rhinitis trajectory groups were identified: 7.6% (n = 59) were termed early transient rhinitis, 8.6% (n = 66) late transient rhinitis, and 6.6% (n = 51) persistent rhinitis. The remaining 77.2% (n = 596) were classified as non-rhinitis/reference group. Early transient rhinitis subjects were more likely of Indian ethnicity, had siblings, reported childcare attendance, early wheezing and eczema in the first 3 years of life. Late transient rhinitis was associated with antenatal exposure to smoking, higher maternal education levels, and wheezing at age 36-72 months. Persistent rhinitis was associated with male gender, paternal and maternal history of atopy, eczema, and house dust mite sensitization. CONCLUSIONS & CLINICAL RELEVANCE: Risk factors for early transient rhinitis involve a combination of genetic and early environmental exposures, whereas late transient rhinitis may relate to maternal factors and early respiratory infections independent of atopy. In contrast, persistent rhinitis is strongly associated with atopic risk and likely represents the typical trajectory associated with allergic disorders. Allergic rhinitis symptoms may commence as early as the first year of life and may inform development of early interventive strategies.

Cohort profile: Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO).

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth, metabolic and neural phenotypes in the offspring. Between February 2015 and October 2017, the S-PRESTO study recruited 1039 Chinese, Malay or Indian (or any combinations thereof) women aged 18-45 years and who intended to get pregnant and deliver in Singapore, resulting in 1032 unique participants and 373 children born in the cohort. The participants were followed up for 3 visits during the preconception phase and censored at 12 months of follow up if pregnancy was not achieved (N = 557 censored). Women who successfully conceived (N = 475) were characterised at gestational weeks 6-8, 11-13, 18-21, 24-26, 27-28 and 34-36. Follow up of their index offspring (N = 373 singletons) is on-going at birth, 1, 3 and 6 weeks, 3, 6, 12, 18, 24 and 36 months and beyond. Women are also being followed up post-delivery. Data is collected via interviewer-administered questionnaires, metabolic imaging (magnetic resonance imaging), standardized anthropometric measurements and collection of diverse specimens, i.e. blood, urine, buccal smear, stool, skin tapes, epithelial swabs at numerous timepoints. S-PRESTO has extensive repeated data collected which include genetic and epigenetic sampling from preconception which is unique in mother-offspring epidemiological cohorts. This enables prospective assessment of a wide array of potential determinants of future health outcomes in women from preconception to post-delivery and in their offspring across the earliest development from embryonic stages into early childhood. In addition, the S-PRESTO study draws from the three major Asian ethnic groups that represent 50% of the global population, increasing the relevance of its findings to global efforts to address non-communicable diseases.

A Novel X-Linked Inhibitor of Apoptosis Deficient Variant Showing Attenuated Epstein-Barr Virus Response.

We report on 2 Asian siblings with X-linked inhibitor of apoptosis deficiency that arose from a novel deletion that presented with Epstein-Barr virus disease and hemophagocytic lymphohistiocytosis. This disease is ascribed to dysfunction in the nucleotide binding and oligomerization domain receptor pathway, tested using a modified muramyl dipeptide-mediated assay.

Cost-effectiveness of two-dose human papillomavirus vaccination in Singapore.

INTRODUCTION: Cervical cancer is the tenth most common cancer and the eighth most frequent cause of death among women in Singapore. As human papillomavirus (HPV) infection is the necessary cause of cervical cancer, the risk of cervical cancer can be substantially reduced through vaccination. This study was conducted to evaluate the cost-effectiveness of two-dose HPV vaccination as part of a national vaccination programme for 12-year-old girls in Singapore, from the perspective of the healthcare payer. METHODS: A lifetime Markov cohort model was used to evaluate the cost-effectiveness of introducing the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18v) to the current cervical screening programme in Singapore. Furthermore, the cost-effectiveness of the AS04-HPV-16/18v was compared with the HPV-6/11/16/18 vaccine (4vHPV). Model inputs were derived from local data, where possible, and validated by clinical experts in Singapore. RESULTS: Introduction of the AS04-HPV-16/18v in Singapore was shown to prevent 137 cervical cancer cases and 48 cervical cancer deaths when compared with screening alone. This resulted in an incremental cost-effectiveness ratio of SGD 12,645 per quality-adjusted life year (QALY) gained, which is cost-effective according to the World Health Organization threshold for Singapore. When discounted at 3%, AS04-HPV-16/18v was dominant over 4vHPV, with cost savings of SGD 80,559 and 28 additional QALYs gained. In the one-way sensitivity analysis, AS04-HPV-16/18v remained cost-effective compared with screening alone and dominant compared with 4vHPV. CONCLUSION: AS04-HPV-16/18v is the most cost-effective choice for reducing the burden of cervical cancer through universal mass vaccination for 12-year-old girls in Singapore.

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9-14 years: Results to month 36 from a randomized trial.

This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or 3D of 4vHPV] in 1075 healthy girls aged 9-14 years. Girls were randomized (1:1:1) to receive 2D of AS04-HPV-16/18 at months (M) 0, 6 (N = 359), 2D of 4vHPV at M0, 6 (N = 358) or 3D of 4vHPV at M0, 2, 6 (N = 358). 351, 339 and 346 girls, respectively, returned for the concluding visit at M36. Superiority was demonstrated at M7 and M12; comparison of the immune response to both vaccine antigens was made between 2D of AS04-HPV-16/18 and 2D or 3D of 4vHPV at subsequent time points in the according-to-protocol immunogenicity cohort (ATP-I; N = 958 at M36) and the total vaccinated cohort (TVC: N = 1036 at M36). HPV-16/18-specific T-cell- and B-cell-mediated immune responses and safety were also investigated. At M36, anti-HPV-16/18 ELISA responses in the 2D AS04-HPV-16/18 group remained superior to those of the 2D and 3D 4vHPV groups. In the M36 TVC, geometric mean titers were 2.78-fold (HPV-16) and 6.84-fold (HPV-18) higher for 2D of AS04-HPV-16/18 vs. 2D of 4vHPV and 2.3-fold (HPV-16) and 4.14-fold (HPV-18) higher vs. 3D of 4vHPV. Results were confirmed by vaccine pseudovirion-based neutralisation assay. Numbers of circulating CD4+ T cells and B cells appeared similar across groups. Safety was in line with the known safety profiles of both vaccines. In conclusion, superior HPV-16/18 antibody responses were elicited by 2D of the AS04-HPV-16/18 compared with 2D or 3D of the 4vHPV vaccine in girls aged 9-14 years. CLINICAL TRIAL REGISTRATION: NCT0146235.

Natural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56bright NKG2A+++ Cells, and Yet Display Increased Degranulation and Higher Perforin Content.

Mutations of the recombinase-activating genes 1 and 2 (RAG1 and RAG2) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell transplantation (HSCT) represents the only curative treatment; however, high rates of graft failure and incomplete immune reconstitution have been observed, especially after unconditioned haploidentical transplantation. Studies in mice have shown that Rag-/- natural killer (NK) cells have a mature phenotype, reduced fitness, and increased cytotoxicity. We aimed to analyze NK cell phenotype and function in patients with mutations in RAG and in non-homologous end joining (NHEJ) genes. Here, we provide evidence that NK cells from these patients have an immature phenotype, with significant expansion of CD56bright CD16-/int CD57- cells, yet increased degranulation and high perforin content. Correlation was observed between in vitro recombinase activity of the mutant proteins, NK cell abnormalities, and in vivo clinical phenotype. Addition of serotherapy in the conditioning regimen, with the aim of depleting the autologous NK cell compartment, may be important to facilitate engraftment and immune reconstitution in patients with RAG and NHEJ defects treated by HSCT.

Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency.

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis. OBJECTIVE: The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID. METHODS: From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study. RESULTS: A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29 patients had a positive FH. Candidiasis (n = 27) and bacillus Calmette-Guérin (BCG) vaccine infection (n = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections were not associated with age or time to diagnosis. CONCLUSION: FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 × 109/L.

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine administered according to 2- and 3-dose schedules in girls aged 9-14 years: Results to month 12 from a randomized trial.

This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of 2 doses of the HPV-16/18 AS04-adjuvanted vaccine (HPV-16/18(2D)) vs. 2 or 3 doses of the HPV-6/11/16/18 vaccine (HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D)) in healthy girls aged 9-14 y. Girls were randomized (1:1:1) to receive HPV-16/18(2D) at months (M) 0,6 (N = 359), HPV-6/11/16/18(2D) at M0,6 (N = 358) or HPV-6/11/16/18(3D) at M0,2,6 (N = 358). The primary objective was non-inferiority/superiority of HPV-16/18 antibodies by ELISA for HPV-16/18(2D) vs. HPV-6/11/16/18(2D) at M7 in the according-to-protocol immunogenicity cohort (ATP-I) and total vaccinated cohort, respectively. Secondary objectives included non-inferiority/superiority of HPV-16/18(2D) vs. HPV-6/11/16/18(3D) at M7, non-inferiority/superiority at M12, HPV-16/18 neutralizing antibodies, frequencies of T-cells/B-cells, reactogenicity and safety. Antibody responses at M7 for HPV-16/18(2D) were superior to those for HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D) (lower limit of 95% confidence interval for geometric mean titer ratio (GMR) was >1): HPV-16/18(2D)/HPV-6/11/16/18(2D) GMRs were 1.69 [1.49-1.91] for anti-HPV-16 and 4.52 [3.97-5.13] for anti-HPV-18; HPV-16/18(2D)/HPV-6/11/16/18(3D) GMRs were 1.72 [1.54-1.93] for anti-HPV-16 and 3.22 [2.82-3.68] for anti-HPV-18; p = 0.0001 for all comparisons. Non-inferiority/superiority was also demonstrated at M12. Among initially seronegative girls in the ATP-I, neutralizing antibody titers were at least 1.8-fold higher for HPV-16/18(2D) vs. HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D) at M7 and M12. Frequencies of HPV-16/18-specific T-cells and B-cells were in similar ranges between groups. Reactogenicity and safety were in line with the known profile of each vaccine. In conclusion, superior HPV-16/18 antibody responses were elicited by 2 doses of the HPV-16/18 AS04-adjuvanted vaccine compared with 2 or 3 doses of the HPV-6/11/16/18 vaccine in girls (9-14 years).

Use of intravenous immunoglobulin in an Asian paediatric population over a 10-year period.

AIMS: There is a paucity of data on the pattern of intravenous immunoglobulin (IVIG) usage in the paediatric population. This study aimed to assess the prevalence, trends, indications and burden of cost of IVIG usage in the Singaporean paediatric population. METHODS: Pharmacy data of all IVIG prescriptions between 2000 and 2009 in the two major paediatric public hospitals in Singapore were retrospectively reviewed. Each prescription was cross-referenced with the patient's hospital records to confirm the administration of IVIG and indication of use. RESULTS: Over the 10-year period, a total 78,155 g of IVIG valued at an estimated $5.2 million was prescribed. There was an increasing trend of 445.6 g/year (P = 0.02) over this period. Analysis of patients showed that the most common indication for IVIG use was Kawasaki disease, both in terms of the proportion of patients (60%) and amount of IVIG used (34%). Kawasaki disease was also the only indication where there were significant increasing trends in both patient numbers (7.4 patients/year) and amount of IVIG used (247.5 g/year). The indications with the highest amount of IVIG used per patient were for conditions related to primary immunodeficiency diseases and stem cell transplantation, where repeat transfusions were required. More than 75% of indications were Food and Drug Administration approved. CONCLUSION: Albeit substantial and increasing, the use of IVIG in Singaporean children is mostly evidence based.

Stem cell transplantation for primary immunodeficiency disease: experience of a singapore hospital.

We retrospectively analyzed the outcomes of hematopoietic stem cell transplantation in 7 patients with primary immunodeficiency diseases treated at the National University Hospital, Singapore, over the period from December 1996 to January 2010. The primary immunodeficiency diseases managed were X-linked hyperimmunoglobulin M syndrome (n = 3), severe combined immunodeficiency (n = 1), leukocyte adhesion deficiency type 1 (n = 1), chronic granulomatous disease (n = 1), and Wiskott-Aldrich syndrome (n = 1). The age of the patients ranged from 5 months to 17 years. Conditioning regimen depended on the type of immunodeficiency, whereas supportive treatment was tailored for differing pretransplant conditions. Eight stem cell transplantations were performed for 7 patients. Donors were HLA-matched sibling donors for 2 patients and unrelated donors for the rest. At the median follow-up of 8.6 years (range 2.2-15.0 years) as of December 2011, 6 patients were alive and cured of their primary diseases.

Manejo nutricional de las intolerancias digestivas más comunes del lactante / Nutritional management of the most common digestive intolerance in infants

Las intolerancias digestivas más comunes del lactante i n c l u y e n e s t r e ñ imi e n t o , r e g u r g i t a c i ó n , llanto/irritabilidad, cólico, gas excesivo y diarrea, que en muchos casos, pueden ser normales, sin embargo, es frecuente ante estas intolerancias, cambiar las fórmulas infantiles. En el presente artículo, un grupo de profesionales de la salud relacionados con la gastroenterología y alergología pediátrica, describen los antecedentes, las definiciones, y el manejo nutricional de cada una de estas intolerancias digestivas.

The most common symptoms of digestive intolerances in infants include constipation, regurgitation,crying/irritability, cramps, excessive gas and diarrhea. Some of these symptoms may be completely normaland are explained in part as a result of the maturation process of the GI tract of young infants. However, it isvery common that parents and doctors due to any of these symptoms switch formulas. A group of experts'pediatric gastroenterologists and pediatric allergists from different countries decided to review this topicand provide practical recommendations.

Rhinitis in children less than 6 years of age: current knowledge and challenges.

Rhinitis is a disease of the upper airway characterized by runny and/or blocked nose and/or sneezing. Though not viewed as a life threatening condition, it is also recognized to impose significant burden to the quality of life of sufferers and their caretakers and imposes an economic cost to society. Through a PubMed online search of the literature from 2006 to September 2011, this paper aims to review the published literature on rhinitis in young children below the age of 6 years. It is apparent from epidemiology studies that rhinitis in this age group is a relatively common problem. The condition has a heterogenous etiology with classification into allergic and non-allergic rhinitis. Respiratory viral infections may play a role in the pathogenesis of long standing rhinitis, but definitive studies are still lacking. Treatment guidelines for management are lacking for this age group, and is a significant unmet need. Although the consensus is that co-morbidities including otitis media with effusion, adenoidal hypertrophy and asthma, are important considerations of management of these children. Pharmacotherapy is limited for young children especially for those below the age of 2 years. This review underscores the lack of understanding of rhinitis in early childhood and therefore the need for further research in this area.

O que é um alergista? / What is an allergist?

Introdução: O alergista é o médico que concluiu com êxito um período de treinamento especializado em alergia e imunologia e um período de treinamento em medicina interna e/ou pediatria. Os alergistas também são imunologistas clínicos especializados, devido à base imunológica das doenças que diagnosticam e tratam. Na maioria dos países, o período aprovado de formação na especialidade em alergia e imunologia é de dois a três anos de treinamento intenso e específico. Dependendo dos sistemas de credenciamento nacionais, a conclusão desse treinamento será reconhecida por um certificado de treinamento especializado em alergia, em alergia e imunologia ou em alergia e imunologia clínica, outorgado por uma comissão diretiva. Em alguns países, isso acompanha a conclusão bem-sucedida de um exame de qualificação e, em outros, as competências apresentadas por um supervisor de treinamento. Os alergistas totalmente treinados fazem uma importante contribuição para o delineamento dos sistemas de atendimento local e proporcionam o atendimento necessário aos pacientes com doenças alérgicas. Os alergistas agem como defensores do paciente, e apóiam e questionam o caso para melhorar a educação dos médicos de atendimento primário e secundário, assim como de outros profissionais de saúde que também atendem pacientes alérgicos. Os alergistas devem estar disponíveis para fazer o atendimento dos casos mais complicados, que estão além do campo de ação de médicos de atendimento primário e secundário e de outros profissionais de saúde com bom treinamento. As principais características que definem um alergista são a apreciação da importância dos desencadeantes externos que causam a doença e o conhecimento de como identificar e tratar essas doenças, juntamente com a experiência nas terapias imunológicas e fármacos apropriados. Essa conduta no diagnóstico e na terapia é um valor essencial do especialista em alergia, e destaca o alergista entre muitos especialistas cujas bases de pacientes podem sobrepor-se com a especialidade...

The Blomia tropicalis allergens.

Blomia tropicalis allergens are the most important mite allergens in tropical regions. Most of them only have 30-40% sequence identity with their Dermatophagoides counterparts and they share low IgE cross reactivity and exhibit different immunobiology. Unlike the pyroglyphid counterparts, Blo t 5 is the major allergen whereas Blo t 1 only has modest allergenicity.

Identification of the major allergenic components in Blomia tropicalis and the relevance of the specific IgE in asthmatic patients.

BACKGROUND: Blomia tropicalis has been reported to be a clinically important allergen in house dust. High prevalence of sensitization to B. tropicalis has been noted in asthmatic patients in Taiwan; however, the allergenic components and its impact on asthmatic patients remain to be clarified. OBJECTIVE: To analyze the prevalence of IgE against B. tropicalis and each allergenic component in asthmatic patients. METHODS: A series of recombinant allergenic components were used for skin tests. The B. tropicalis specific IgE in the serum were measured using the Pharmacia CAP System and immunoblot analysis. RESULTS: A total of 131 patients were included in this study: 44% of these 131 patients were allergic to B. tropicalis, 43% of the 80 B. tropicalis-sensitive patients were allergic to Blo t 5, and 75% of the 65 Blo t 5-sensitive patients were allergic to Blo t 5 fragment 3 (Blo t 5 70-117). The sera IgE binding activity to B. tropicalis was repeatedly tested after Dermatophagoides pteronyssinus absorption, and results showed that most patients were concurrently sensitized to D. pteronyssinus and B. tropicalis. In addition, in 2 (18%) of 11 patients, the B. tropicalis sensitization was caused by the cross-reactivity of D. pteronyssinus. CONCLUSION: A high prevalence of B. tropicalis sensitization was detected in our asthmatic patients, and most of them were concurrently sensitized to D. pteronyssinus and B. tropicalis. The major allergenic component and its IgE binding fragments in Blo t 5 have been identified. These allergenic components can be used for the allergenic determination in B. tropicalis and for further immunotherapy.

Allergen sensitization to aeroallergens including Blomia tropicalis among adult and childhood asthmatics in Thailand.

To study prevalence of allergen sensitization among asthmatics in Thailand, skin prick tests (SPT) were performed in 84 pediatric, 71 adult asthmatics and 71 adult volunteers. Allergen extracts used for testing included common allergens in Thailand and in Singapore. The incidence of positive SPT to any allergen among the three groups (childhood, adult patients and adult controls) were 64.3%, 43.7% and 35.2%, respectively. Dermatophagoides were the most common allergens sensitized by both pediatric (58.3%) and adult asthmatics (40.8%). Twenty-four children (28.6%) and 8 adult patients (11.3%) were sensitized to storage mites (Blomia tropicalis and/or Austroglyciphagus malaysiensis). All patients sensitized to Blomia tropicalis were sensitized to Dermatophagoides. Twenty-seven percent and 15.5% of childhood and adult asthmatics were sensitized to cockroach allergens. The rates of sensitization to oil palm pollen in childhood and adult asthmatics were 8.3% and 5.6%, respectively. Sensitization to other pollens and spores were less than 5%. This study confirms the importance of Dermatophagoides among Thai asthmatics.