Staphylococcal enterotoxin B as DNA vaccine against breast cancer in a murine model / Enterotoxina B estafilocócica como vacuna de ADN contra el cáncer de mama en un modelo murino

Recently, many efforts have been made to treat cancer using recombinant bacterial toxins and this strategy has been used in clinical trials of various cancers. Therapeutic DNA cancer vaccines are now considered as a promising strategy to activate the immune system against cancer. Cancer vaccines could induce specific and long-lasting immune responses against tumors. This study aimed to evaluate the antitumor potency of the SEB DNA vaccine as a new antitumor candidate against breast tumors in vivo. To determine the effect of the SEB construct on inhibiting tumor cell growth in vivo, the synthetic SEB gene, subsequent codon optimization, and embedding the cleavage sites were sub-cloned to an expression vector. Then, SEB construct, SEB, and PBS were injected into the mice. After being vaccinated, 4T1 cancer cells were injected subcutaneously into the right flank of mice. Then, the cytokine levels of IL-4 and IFN-γ were estimated by the ELISA method to evaluate the antitumor activity. The spleen lymphocyte proliferation, tumor size, and survival time were assessed. The concentration of IFN-γ in the SEB-Vac group showed a significant increase compared to other groups. The production of IL-4 in the group that received the DNA vaccine did not change significantly compared to the control group. The lymphocyte proliferation increased significantly in the mice group that received SEB construct than PBS control group (p < 0.001). While there was a meaningful decrease in tumor size (p < 0.001), a significant increase in tumor tissue necrosis (p < 0.01) and also in survival time of the animal model receiving the recombinant construct was observed.(AU)

Induction of killing of Mycobacterium avium subsp. hominissuis in macrophages by cytokine stimulated innate-like lymphoid cells is negatively affected by the pathogen / Inducción de la destrucción de Mycobacterium avium subsp. hominissuis en macrófagos por células linfoides de tipo innato estimuladas por citoquinas se ve afectado negativamente por el patógeno

Mycobacterium avium subsp. hominissuis (MAH) is a common environmental bacterium that causes infection in immunocompromised patients such as those with HIV/AIDS, or patients with chronic lung disease such as cystic fibrosis. There are many strains of MAH with varying levels of virulence. Infection with MAH strains 100 and 104 has been associated with different immune responses in mice and outcome of the disease. While MAH 100 infection tends to be cleared from mice, MAH 104 is virulent and grows in host tissue. What is currently unknown are the mechanisms related to this difference in host defense and virulence. Our hypothesis is that differences in circulating innate lymphocytes response are associated with increased protection from infection. Innate lymphoid cells (ILC) are lymphoid cells with an important role in regulation of innate immune systems. ILCs can be categorized into three subpopulations ILC1, ILC2, and ILC3 based on their cytokine production and regulatory transcription factors. Investigation was carried out on how macrophage anti-MAH response change depending on activation by primary mouse lymphocytes activated with IL-12, IL-33, and IL-23, triggering differentiation into ILC-like subpopulations. Our results do not affirm the role of any one ILC subpopulation in macrophage anti-M. avium ability. Our findings instead support the conclusion that MAH infection of macrophages suppresses the stimulatory function of ILCs.(AU)

HSF1 expression in tumor-associated macrophages promotes tumor cell proliferation and indicates poor prognosis in esophageal squamous cell carcinoma

Purpose Tumor-associated macrophages (TAMs), are crucial for the survival and development of tumor cells. Heat shock factor 1 (HSF1) is a potent, complex carcinogenesis modulator, and esophageal cancer (EC) patients have a bad prognosis when HSF1 is highly expressed. HSF1's clinical importance and biological role in TAMs are still unknown. Methods The HSF1 expression profile and patient survival information were analyzed from the TCGA database. The infiltration of different types of immune cells in EC was evaluated based on HSF1 gene expression by Sangerbox 3.0. Immunochemistry was employed to assess HSF1 protein expression in 134 individuals with esophageal squamous cell carcinoma (ESCC), proceeded by association with clinicopathological variables. The role of macrophage-driven HSF1 were observed using HSF1-knockdown THP1 cells. Results High level of HSF1 have a poorer prognosis in individuals with EC. The expressing level of HSF1 was positively related to infiltration of M2 macrophages (P < 0.05). The expression of HSF1 in macrophages was an independent factor for DFS (P = 0.002) and OS (P = 0.002) in ESCC cases. HSF1 was up-regulated in IL-4 stimulation THP1 cells in a time-dependent manner. Under the heat stimulation condition, THP1-derived macrophages were more sensitive than tumor cells. Compared to IL-4 induced-THP1 cells control, the HSF1 knockdown in THP1 cell inhibited the growth and proliferation of ESCC cells. Conclusions The up-regulation of HSF1 was more rapid and could affect the proliferation of tumor cells in IL4-induced macrophages. The expression of HSF1 in TAMs can also serve as a marker for ESCC prognosis (AU)

IL-6 secretion of CD4+ T cells stimulated by LC3-positive extracellular vesicles in human epithelial ovarian cancer

Ovarian cancer (OC) as the most fatal gynecological malignancy worldwide, with epithelial ovarian cancer (EOC) being the predominant and most lethal form, poses a serious threat to human health. LC3-positive extracellular vesicles (LC3+ EVs) promote tumorigenesis by educating CD4+ T cells in a murine melanoma model. However, regulation of LC3+ EVs in human EOC remains largely unknown. MethodsDifferential analysis of Rab8a, Hsp90α and Il6 expression was performed using GEPIA2. The number of LC3+ EVs and the frequency of Heat shock protein 90α+ LC3+ EVs (HSP90α+ LC3+ EVs) in the ascites of EOC patients were tested by flow cytometry. IL-6, IL-10, IFN-γ, IL-4 and TGF-β were measured by ELISA. CD4+ T cells were isolated from peripheral blood of healthy human donors using MACS magnetic bead technology. ResultsHigher Rab8a, Hsp90a and Il6 expression of cancer tissues compared with normal adjacent tissues in OC were found. The level of IL-6 was positively correlated with LC3+ EVs number, HSP90α+ LC3+ EVs percentage in the ascites, and ROMA index of the patient. In addition, elevated IL-6 production by CD4+ T cells induced by LC3+ EVs was observed, which was suppressed by anti-HSP90α or anti-TLR2. ConclusionsLC3+ EVs level and HSP90α+ LC3+ EVs percentage were associated with elevated IL-6 in the ascites of EOC patients. HSP90α on LC3+ EVs from human EOC could stimulate CD4+ T cell production of IL-6 via TLR2. (AU)

Anti-inflammatory effect of N-(trifluoromethylphenyl)- 2-cyano-3-hydroxy-crotonic acid amide and gluconic acid on allergic rhinitis and asthma controlling

Allergic rhinitis and asthma are the main airway diseases with a higher prevalence. Eosinophilic inflammation, airway hyperresponsiveness, mucus hypersecretion, and reversible airflow obstruction are immunopathogenesis symptoms of rhinitis and asthma. Crotonic acid has bio-activity on the inflammation, and gluconic acid as chelator may protect crotonic acid activity in airway and together may control allergic rhinitis and asthma. Allergic rhinitis and asthma mice models were treated with crotonic and gluconic acids. The total IgE, histamine, IL-4, IL-5, and IL-13 levels were measured. In lung tissues, goblet cell hyperplasia, mucus hypersecretion, and inflammation were evaluated. The level of IL-5, goblet cell hyperplasia, and perivascular and peribronchial inflammation were controlled by crotonic acid in asthma and allergic rhinitis groups. But, total IgE, hista-mine, IL-4, and IL-13 levels, and mucus hypersecretion had no significant changes between treated and nontreated asthma and rhinitis groups. Crotonic acid can control eosinophilic inflammation via harnessing IL-5 and preventing goblet cell hyperplasia. When used with gluconic acid, it had a strong effect on the control of allergic rhinitis and asthma immunopathologies (AU)

Study on the antipruritic mechanism of Zanthoxylum bungeanum and Zanthoxylum schinifolium volatile oil on chronic eczema based on H1R and PAR-2 mediated GRPR pathway

Objective: To observe the antipruritic effect and mechanism of the volatile oil of Zanthoxylum bungeanum and Zanthoxylum schinifolium on chronic eczema to provide data support for clinical application and new drug development of Zanthoxylum bungeanum and Zanthoxylum schinifolium. Methods: The model of chronic eczema was established by using 2-dinitrochlorobenzene (DNCB), and the composition and content of volatile oil in Zanthoxylum schinifolium and Zanthoxylum bungeanum was determined by gas chromatography-mass spectrometry (GC-MS). The antipruritic effect by (EASI) score of eczema area and severity index and scratching times was then evaluated. Then, the contents of histamine, gastrin-releasing peptide (GRP), interleukin-4 (IL-4), and immunoglobulin E (IgE) in serum of rats was determined by enzyme-linked immunosorbent assay (ELISA). The tissue morphology was observed by HE staining. The expressions of H1R, PAR-2, TRPV1, TRPA1, and GRPR was then detected by immunohistochem-istry, Western blot, and QRT-PCR.Results: The results revealed that there were differences in the composition of volatile oil between Zanthoxylum bungeanum and Zanthoxylum schinifolium. Compared to the model group, the medium-dose group of Zanthoxylum bungeanum and Zanthoxylum schinifolium group significantly increased the difference of EASI score and scratching times, significantly decreased the concentrations of IL-4, IgE, GRP, and histamine, and significantly decreased the expression levels of H1R, PAR-2, TRPV1, and GRPR. The degree of inhibition on the patho-logical manifestations of chronic eczema was evident. There was no significant difference in antipruritic effect between the two groups. The expression of TRPA1 was inconsistent at the protein and gene level, which needs to be further researched (AU)

Correlation analysis of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in refractory chronic rhinosinusitis: A retrospective study

Objective: To investigate the potential correlation of transforming growth factor-β (TGF-β), matrix metalloprotein 9 (MMP-9), tissue inhibitor of metalloproteinases 1 (TIMP-1), Interleukin 1 (IL-1), IL-4, IL-6, IL-17, and tumor necrosis factor alpha (TNF-α) in refractory chronic rhinosinusitis.Methods: A total of 150 participants were retrospectively included in this study from August 2018 to February 2020. The people enrolled were equally allocated into refractory group (patients with refractory chronic rhinosinusitis), chronic group (patients with chronic rhinosi-nusitis), and control group (normal people). The level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α were recorded. The unconditional multivariate binary logistic regression was used to analyze the factors affecting refractory chronic rhinosinusitis.Results: The Davos score, T&T olfactometer threshold test, and Lund-Mackay CT scores in refractory group were significantly higher than the chronic group (P<0.05). The level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in the refractory group were significantly higher than the chronic group and the control group (all P<0.05). Similarly, the level of the above mentioned indexes in the chronic group were significantly higher than the control group (P<0.05). The Davos score, T&T olfactometer threshold test score, Lund-Mackay CT score, and the level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α positively correlated with refractory chronic rhinosinusitis. Moreover, the unconditional multivariate binary logistic regression showed that the influencing factors of refractory chronic rhinosinusitis included TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α.Conclusion: The findings of the present study provide evidence for TGF-β1, MMP-9, TIMP-1, IL-4, IL-6, IL-17, and TNF-α as the influencing factors of refractory chronic rhinosinusitis (AU)

Association between the type of allergen and T-helper 2 mediated inflammation in allergic reactions: a systematic review and a meta-analysis

Objectives To determine whether the levels of T-helper (TH) 2 cytokines (interleukin (IL)-4 and IL-5) in allergic reactions are allergen dependent and evaluate the impact of various treatment strategies on the levels of these cytokines.Methods The PubMed search engine was used from inception until January 2021. The random-effects residual maximum likelihood model was performed, and effect sizes were estimated using the Hedge’s g statistic. All data analysis was performed using STATA 16.0 (StataCorp LP, TX, USA).Results Fourteen studies reporting on 794 participants were included in this study. House dust mite was associated with eliciting a stronger immune response mediated by both IL-4 and IL-5 when compared to pollen. Whereas a mixture of house dust mite and pollen was associated with IL-4-weighted inflammation. Comparisons of IL-4 and IL-5 levels amongst the allergens showed significant differences. The treatment with anti-corticosteroids or allergen-specific immunotherapy was effective in normalising the TH2 responses and alleviating allergy symptoms (AU).

Role of interleukin-4 in pathogenesis of oral lichen planus: A systematic review

BACKGROUND: Oral lichen planus (OLP) is a premalignant mucocutaneous disease that affects 1-2% of the adult population. Immunological factor may act as etiological factor. The cellular immune cells such as T cells are important in pathogenesis of OLP. Interleukin-4 (IL-4) is secreted by T-helper 2 (Th2). Several studies have been carried out on the role of IL-4 in OLP. The aim of this study was to review the level of IL-4 in OLP, effective factors in the production of IL-4 and its role in the development of OLP. MATERIAL AND METHODS: A search in PubMed was performed on the literature published from 2000 until august 2019 using the following keywords: "oral lichen planus" or "OLP" and "interleukin-4" or "IL-4". RESULTS: Originally, 37 articles were considered, of which 28 case-control articles were selected according to the inclusion/exclusion criteria. CONCLUSIONS: This review study shows that IL-4 plays a key role in the development of OLP. According to the past studies, there are several factors contributing to the production of this cytokine. Identification of the routes of production of IL-4 and its role in OLP might be useful for development of new preventive and therapeutic methods in management of patients with OLP

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Novedades en las guías sobre el tratamiento del asma grave / The latest developments in the guidelines on severe asthma treatment

Las guías de práctica clínica (GPC) aparecieron con el fin de homogenizar el diagnóstico y tratamiento del asma; inicialmente como un consenso de expertos, y posteriormente incluyendo para sus afirmaciones y recomendaciones técnicas de medicina basada en la evidencia, e incorporar en sus actualizaciones frecuentes, los cambios en el conocimiento fisiopatológico y en el manejo de la enfermedad. En el 2019 se han realizado actualizaciones de las tres principales GPC incluyendo el tratamiento del paciente con asma grave no controlada, el uso de fármacos biológicos y otros procedimientos

The clinical practice guidelines (CPG) appeared with the intention to homogenize the asthma diagnosis and treatment, initially as an expert consensus, and afterwards including evidence based medicine data for its affirmations and technical recommendations incorporating advances in knowledge and management of the disease in their frequent updates. In 2019 the 3 principal CPG, have updates including the management of non-controlled severe asthma patients, biological treatments use and other procedures

Atopy can be an interfering factor in genetic association studies of beta-lactam allergy

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Adherence to the Mediterranean diet and inflammatory markers in children with asthma

Introduction: There is accumulated evidence supporting a beneficial role of Mediterranean diet (MD) in the control of asthma symptoms. The aim of this study was to investigate the relationships between adherence to MD and serum levels of certain cytokines namely, interleukin (IL)-4, and IL-17 known to have a pathogenetic role in the airway changes associated with asthma. Methods: We measured serum IL-4, IL-33, and IL-17, in 44 asthmatic and 26 healthy children, 5-15 years old. Their adherence to MD was estimated with the Mediterranean Diet Quality Index for children and adolescents (KIDMED) score. Results: KIDMED score did not differ between the two groups (P = 0.59) and was not correlated with any of the three measured cytokines. However, when the analysis was restricted only to asthmatic children, the KIDMED score was correlated with IL-4, IL-33, and IL-17 (Beta: -0.56, P = 0.007; Beta: 0.57, P = 0.010; Beta: -0.62, P = 0.017, respectively). Conclusion: Our results indicate that MD can modulate the production of some of the main inflammatory mediators of asthma, in asthmatic children

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Correlation of OX40 ligand on B cells with serum total IgE and IL-4 levels by CD4+ T cells in allergic rhinitis

Introduction and objectives: Allergic rhinitis (AR) is a classic Th2-mediated disease, with important contributions to the pathology of interleukins 4, 5, and 13. The co-stimulatory molecule of OX40 and its ligand interaction participate in the immune response by regulation of Th1/Th2 cells balance. Considering the paucity of information on the relation between OX40 ligand (OX40L) and AR, this study aimed to examine its expression on B lymphocytes. Patients and methods: This case-control study consisted of 20 AR patients and 20 healthy subjects. The serum level of total immunoglobulin E (IgE) was measured using the electro-chemiluminescence (ECL) technology. The percentage of B-lymphocytes expressing OX40L was assessed by flow cytometry. The amounts of IL-4 in CD4+ T cells culture supernatant was also measured by the enzyme-linked immunosorbent assay (ELISA). Results: OX40L expression on B lymphocytes of patients was significantly higher than the control group (44.32 ± 19.21% vs. 2.79 ± 2.48% respectively, p < 0.001). In AR patients, OX40L expression correlated positively with the levels of serum total IgE and IL-4 produced by CD4+ T lymphocytes (p < 0.01 - p < 0.05) respectively. Conclusions: Collectively, the findings of this work suggest that there is a relationship between the OX40L expression level on B lymphocytes and allergic markers such as IgE and IL-4 in patients with allergic rhinitis

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The profile of IL-4, IL-5, IL-10 and GATA3 in patients with LRBA deficiency and CVID with no known monogenic disease: Association with disease severity

Background: Common variable immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiency (PID). LPS-responsive beige-like anchor protein (LRBA) deficiency is an autosomal recessive disease characterized by a CVID-like phenotype. T cell abnormality was reported in patients with CVID and LRBA deficiency. The study's aim was to evaluate IL-4, IL-5, IL-10 and GATA3 expression in patients with LRBA deficiency and CVID with no known monogenic disease, and further evaluate its relevance with immunological futures and clinical complications of patients. Methods: The study population comprised patients with CVID, LRBA deficiency and age-sex matched healthy controls. Mutation analysis was done by whole exome sequencing in CVID patients to rule out monogenic PIDs. After CD4+ T cell stimulation with anti-CD3 and anti-CD28 monoclonal antibodies, gene expression of IL-4, IL-5, IL-10 and transcription factor GATA3 was evaluated by real-time polymerase chain reaction. The protein of mentioned cytokines was assessed by enzyme-linked immunosorbent assay. Results: The main clinical presentations of CVID patients were infections only and lymphoproliferations phenotypes, but in LRBA patients were autoimmune and enteropathy phenotype. The frequencies of CD4+ T cells were significantly reduced in LRBA and CVID patients. There were no statistically significant differences among GATA3, IL4, and IL5 gene expressions by CD4+ T cells of patients and controls, however, the IL10 expressions in CVID patients was significantly lower than in LRBA patients and HCs. As compared with HCs, CVID patients showed a prominent decrease in IL-4 and IL-10 production by CD4+ T cells. Conclusions: Our findings demonstrated that patients with CVID and LRBA deficiency (even with severe infectious and inflammatory complications) have not imbalance in Th2 response, which is in parallel with lower frequency of allergy and asthma in these patients

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Dupilumab para el tratamiento de la dermatitis atópica / Dupilumab for the Treatment of Atopic Dermatitis

La dermatitis atópica (DA) es una frecuente enfermedad crónica e inflamatoria de la piel que acarrea una fuerte carga física y emocional. La DA suele comenzar a edades tempranas y tiene un curso heterogéneo. Las últimas evidencias a este respecto sugieren que las interleucinas IL-4 e IL-3 son citoquinas claves en la inmunopatogénesis de la DA. El dupilumab es un anticuerpo monoclonal dirigido contra la subunidad del receptor alfa de la IL-4 que bloquea la señalización tanto de la IL-4 como de la IL-3. Datos extraídos de estudios fase i-iii revelan que administrado como monotratamiento o acompañado de corticosteroides tópicos, el dupilumab se tolera bien y resulta efectivo en el tratamiento de pacientes adultos con DA de carácter entre moderado y grave. Un gran número de pacientes que recibieron dupilumab experimentaron mejorías notables en varios índices de eficacia, incluidos el Índice de gravedad y área de eccema, la Escala de evaluación global del investigador y la Escala de dermatitis atópica. Estos resultados abren una nueva era a tratamientos dirigidos en el manejo de la DA

Atopic dermatitis (AD) is a common, chronic, inflammatory skin disorder with high physical and emotional burden. AD usually starts in early childhood and has a heterogeneous course. Emerging evidence suggests that IL-4 and IL-13 are key cytokines in the immunopathogenesis of AD. Dupilumab is a monoclonal antibody directed against IL-4 receptor α subunit, that blocks both IL-4 and IL-13 signaling. Data from Phase I-III studies revealed that dupilumab, administered as monotherapy or with topical corticosteroids, is effective and well tolerated in the treatment of adult patients with moderate-to-severe AD. A large proportion of patients receiving dupilumab had significant improvements in multiple efficacy indexes, including Eczema Area and Severity Index, Investigator's Global Assessment and SCORing Atopic Dermatitis scores. These results introduce a new era of targeted therapies in the management of AD

Dupilumab: a new paradigm for the treatment of allergic diseases

Moderate and severe forms of allergic diseases such as atopic dermatitis and asthma are a challenge for clinicians. In these conditions, which severely affect the quality of life of the patient and frequently have associated allergic comorbidities, the therapeutic options are often very limited. Treatment with systemic corticosteroids and immunosuppressants has adverse effects in the long term, and a significant proportion of patients remain refractory to therapy. In this context, the emerging biological drugs constitute a truly innovative therapeutic approach. A leading example is dupilumab, a monoclonal antibody targeting the α chain of the interleukin (IL)-4 receptor. Dupilumab inhibits the biological effects of the cytokines IL-4 and IL-13, which are key drivers in the TH2 response. The efficacy and safety profile of dupilumab in the treatment of allergic diseases has been tested for more than 10 years in a variety of large clinical trials in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis. In 2017, the United States Food and Drug Administration and the European Medicines Agency approved the use of dupilumab for the treatment of adult patients with moderateto-severe atopic dermatitis whose disease is not adequately controlled with prescribed topical treatment. The results of phase III clinical studies of dupilumab in patients with persistent, uncontrolled asthma have been highly promising. The safety and tolerability profile of dupilumab has proven to be very favorable in long-term clinical trials. In this review, we focus on the mechanism of action of dupilumab, its development, and its impact on daily clinical practice in allergic diseases

Las formas clínicas moderadas y graves de enfermedades alérgicas comunes como la dermatitis atópica o el asma constituyen un reto para los clínicos. En estos casos, que afectan intensamente la calidad de vida del paciente y con frecuencia conllevan otras enfermedades alérgicas asociadas, las opciones terapéuticas son a menudo muy limitadas. El tratamiento con corticosteroides sistémicos o inmunosupresores tiene efectos adversos a largo plazo y una proporción significativa de pacientes se muestra refractaria a la terapia. En este contexto, los nuevos fármacos biológicos, dirigidos a la base inmunológica de la enfermedad, ofrecen un enfoque terapéutico verdaderamente innovador. Un ejemplo destacado de estos fármacos es dupilumab, un anticuerpo monoclonal dirigido contra la cadena alfa del receptor de la interleucina (IL)-4. Dupilumab inhibe los efectos biológicos de las citoquinas IL-4 e IL-13, unos de los principales efectores de la respuesta Th2. La efectividad y seguridad de dupilumab en el tratamiento de enfermedades alérgicas se han probado durante más de diez años en una variedad de grandes ensayos clínicos en dermatitis atópica, asma, rinosinusitis crónica con poliposis nasal y esofagitis eosinofílica. La FDA y la EMA aprobaron en 2017 el uso de dupilumab en el tratamiento de pacientes adultos con dermatitis atópica moderada o grave que no se controla adecuadamente con tratamiento tópico. Los estudios clínicos de Fase 3 de dupilumab en pacientes con asma persistente no controlada también han sido muy prometedores. En los ensayos clínicos a largo plazo la seguridad y tolerabilidad de dupilumab ha demostrado ser muy elevada. En esta revisión nos hemos centrado en el mecanismo de acción de dupilumab, su desarrollo como fármaco y su impacto en la terapia de enfermedades alérgicas

Association of a 4-locus gene model including IL13, IL4, FCER1B, and ADRB2 with the asthma predictive index and atopy in Chinese Han children

Background: Asthma is a complex and heterogeneous disease. We found gene-gene interactions between IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 in asthmatic Chinese Han children. This 4-locus set constituted an optimal statistical interaction model. Objective: We examined associations between the 4-gene model (IL13, IL4, FCER1B, and ADRB2) and the Asthma Predictive Index (API) and atopy in Chinese Han children. Methods: Four single-nucleotide polymorphisms in the 4 genes were genotyped in 385 preschool children with wheezing symptoms using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The t test and x2 tests were used for the analysis. Results: Significant correlations were found between the 4-locus gene model and a stringent and loose API (both P<.0001). Additionally, a high-risk asthma genotype was a risk factor for a positive API (stringent API, OR=4.08; loose API, OR=2.36). We also found a statistically significant association between the 4-locus gene model and atopy (P<.01, OR=2.09). Conclusions: Our results indicated that the 4-locus gene model consisting of L13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was associated with the API and atopy. These findings provide evidence that this gene model can be used to determine a high risk of developing asthma and atopy in Chinese Han children

Antecedentes: El asma es una enfermedad compleja y heterogénea. En este estudio, encontramos que las interacciones gen-gen entre IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713 y FCER1B rs569108, en niños asmáticos de nacionalidad china Han, constituyen un modelo estadístico óptimo de interacción. Objetivo: Este estudio examinó un modelo de las asociaciones de cuatro genes (IL13, IL4, FCER1B y ADRB2) con el Índice Predictivo de Asma (IPA) y la atopia en niños Han chinos. Métodos: Se genotiparon cuatro polimorfismos de un solo nucleótido (SNP) en los cuatro genes, en 385 niños en edad preescolar con síntomas de sibilancias, utilizando espectrometría de masas con desorción/ionización mediante láser asistida por Matriz (MALDI). Para el análisis estadístico de utilizaron el test t de Student y el c2. Resultados: Se encontraron correlaciones significativas entre el modelo génico de los cuatro locus y el valor de IPA estricto y laxo (ambos P <0,0001). Además, el genotipo de riesgo alto de asma fue un factor de riesgo para IPA positivo (IPA estricto: OR = 4,08, IPA laxo: OR = 2,36). También, encontramos una asociación estadísticamente significativa entre el modelo génico de los cuatro locus, con atopia (P <0,01, OR = 2,09). Conclusiones: Nuestros resultados indicaron que el modelo génico de cuatro locus compuesto por L13 rs20541, IL4 rs2243250, ADRB2 rs1042713 y FCER1B rs569108 estaba asociado con IPA y atopia. Estos hallazgos proporcionan la evidencia de la utilidad de este modelo génico para determinar el riesgo alto de desarrollar asma y atopia en niños chinos Han