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BACKGROUND: CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) is an ultra-rare genetic disorder characterised by intestinal lymphatic damage, lymphangiectasia, and protein-losing enteropathy caused by overactivation of the complement system. We assessed the efficacy and safety of pozelimab, an antibody blocking complement component 5. METHODS: This open-label, single-arm, historically controlled, multicentre phase 2 and 3 study evaluated ten patients with CHAPLE disease. This study was conducted at three hospitals in Thailand, Türkiye, and the USA. Patients aged 1 year or older with a clinical diagnosis of CHAPLE disease and a CD55 loss-of-function variant identified by genetic analysis and confirmed by flow cytometry or western blot of CD55 from peripheral blood cells were eligible for this study. Patients received a single intravenous loading dose of pozelimab 30 mg per kg of bodyweight, followed by a once-per-week subcutaneous dose over the treatment period based on bodyweight at a concentration of 200 mg/mL as either a single injection (<40 kg bodyweight) or two injections (≥40 kg bodyweight). The primary endpoint was proportion of patients with serum albumin normalisation with an improvement in active clinical outcomes and no worsening in inactive clinical outcomes (frequency of problematic abdominal pain, bowel movement frequency, facial oedema severity, and peripheral oedema severity) at week 24 compared with baseline, assessed in the full analysis set. This study is registered with ClinicalTrials.gov (NCT04209634) and is active but not recruiting. FINDINGS: 11 patients were recruited between Jan 27, 2020, and May 12, 2021, ten of which were enrolled in the study and included in the analysis populations. The efficacy data corresponded to all patients completing the week 48 assessment and having at least 52 weeks of treatment exposure, and the safety data included an additional 90 days of follow-up and corresponded to all patients having at least 72 weeks of treatment. Patients were predominantly paediatric (with a median age of 8·5 years), and originated from Türkiye, Syria, Thailand, and Bolivia. Patients had markedly low weight-for-age and stature-for-age at baseline, and mean albumin at baseline was 2·2 g/dL, which was considerably less than the local laboratory reference range. After pozelimab treatment, all ten patients had serum albumin normalisation and improvement with no worsening in clinical outcomes. There was a complete inhibition of the total complement activity. Nine patients had adverse events; two were severe events, and one patient had an adverse event considered related to pozelimab. INTERPRETATION: Pozelimab inhibits complement overactivation and resolves the clinical and laboratory manifestations of CHAPLE disease. Pozelimab is the only currently approved therapeutic drug for patients with this life-threatening, ultra-rare condition. In patients with protein-losing enteropathy where known causes have been excluded, testing for a CD55 deficiency should be contemplated. A diagnosis of CHAPLE disease should lead to early consideration of treatment with pozelimab. FUNDING: Regeneron Pharmaceuticals and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
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Enteropatias Perdedoras de Proteínas , Trombose , Criança , Humanos , Anticorpos Monoclonais , Edema , Enteropatias Perdedoras de Proteínas/tratamento farmacológico , Albumina Sérica , Resultado do Tratamento , Estudo Historicamente Controlado , Masculino , FemininoRESUMO
PURPOSE: Deficiency of stromal interaction molecule 1 (STIM1) results in combined immunodeficiency accompanied by extra-immunological findings like enamel defects and myopathy. We here studied a patient with a STIM1 loss-of-function mutation who presented with severe lymphoproliferation. We sought to explore the efficacy of the mTOR inhibitor rapamycin in controlling disease manifestations and reversing aberrant T-cell subsets and functions, which has never been used previously in this disorder. METHODS: Clinical findings of the patient were collected over time. We performed immunological evaluations before and after initiation of rapamycin treatment, including detailed lymphocyte subset analyses, alterations in frequencies of circulating T follicular helper (cTFH) and regulatory T (Treg) cells and their subtypes as well as T cell activation and proliferation capacities. RESULTS: A novel homozygous exon 2 deletion in STIM1 was detected in a 3-year-old girl with severe lymphoproliferation, recurrent infections, myopathy, iris hypoplasia, and enamel hypoplasia. Lymphoproliferation was associated with severe T-cell infiltrates. The deletion resulted in a complete loss of protein expression, associated with a lack of store-operated calcium entry response, defective T-cell activation, proliferation, and cytokine production. Interestingly, patient blood contained fewer cTFH and increased circulating follicular regulatory (cTFR) cells. Abnormal skewing towards TH2-like responses in certain T-cell subpopulations like cTFH, non-cTFH memory T-helper, and Treg cells was associated with increased eosinophil numbers and serum IgE levels. Treatment with rapamycin controlled lymphoproliferation, improved T-cell activation and proliferation capacities, reversed T-cell responses, and repressed high IgE levels and eosinophilia. CONCLUSIONS: This study enhances our understanding of STIM1 deficiency by uncovering additional abnormal T-cell responses, and reveals for the first time the potential therapeutic utility of rapamycin for this disorder.
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Doenças Musculares , Sirolimo , Feminino , Humanos , Pré-Escolar , Molécula 1 de Interação Estromal/genética , Subpopulações de Linfócitos T , Imunoglobulina E , Proteínas de NeoplasiasRESUMO
BACKGROUND: Immunoglobulin G replacement therapy (IgRT), intravenous (IV) and subcutaneous (SC) routes, is pivotal in treatment of primary immunodeficiencies (PID). In recent years, facilitated subcutaneous immunoglobulin (fSCIG), a combination of rHuPH20 and 10% IgG has emerged as a delivery method to combine advantages of both IV and SC. METHOD: In an observational prospective cohort, we investigated patient experience with fSCIG in PID patients from 5 PID centers for up to 12 months. We assessed the efficacy and safety of this treatment with patient/caregiver- and physician-reported indicators. Additionally, we analyzed patient treatment satisfaction (TSQM-9) and quality of life (QoL). RESULTS: We enrolled 29 patients (22 pediatric and 7 adults; 14 females and 15 males; (median: 15, min-max: 2-40.9 years) who initiated fSCIG as IgRT-naive (n = 1), switched from conventional rapid-push 10% SCIG (n = 6) or IVIG (n = 22). Among the participants, 19 (65%) exhibited antibody deficiencies, 8 (27%) combined immunodeficiencies, and 2 (7%) immune dysregulations. Remarkably, targeted trough immunoglobulin G levels were achieved under all previous IgRTs as well as fSCIG. No severe systemic adverse drug reactions were documented, despite prevalent local (%86.45) and mild systemic (%26.45) adverse reactions were noted with fSCIG. Due to mild systemic symptoms, 2 patients switched from fSCIG to 10% SCIG. The patient satisfaction survey revealed a notable increase at 2-4th (p = 0.102); 5-8th (p = 0.006) and 9-12th (p < 0.001) months compared to the baseline. No significant trends were observed in QoL surveys. CONCLUSION: fSCIG demonstrates admissable tolerability and efficacy in managing PIDs in addition to notable increase of patients' drug satisfaction with IgRT. The identified benefits support the continuation of this therapy despite the local reactions.
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Imunoglobulina G , Imunoglobulinas Intravenosas , Satisfação do Paciente , Qualidade de Vida , Humanos , Masculino , Feminino , Criança , Estudos Prospectivos , Adulto , Pré-Escolar , Adolescente , Adulto Jovem , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulina G/uso terapêutico , Doenças da Imunodeficiência Primária/terapia , Resultado do Tratamento , Injeções Subcutâneas , Infusões Subcutâneas , Síndromes de Imunodeficiência/terapia , Síndromes de Imunodeficiência/tratamento farmacológicoRESUMO
Loss of function mutations in Diaphanous related formin 1 (DIAPH1) are associated with seizures, cortical blindness, and microcephaly syndrome (SCBMS) and are recently linked to combined immunodeficiency. However, the extent of defects in T and innate lymphoid cells (ILCs) remain unexplored. Herein, we characterized the primary T, natural killer (NK) and helper ILCs of six patients carrying two novel loss of function mutation in DIAPH1 and Jurkat cells after DIAPH1 knockdown. Mutations were identified by whole exome sequencing. T-cell immunophenotyping, proliferation, migration, cytokine signaling, survival, and NK cell cytotoxicity were studied via flow cytometry-based assays, confocal microscopy, and real-time qPCR. CD4+ T cell proteome was analyzed by mass spectrometry. p.R351* and p.R322*variants led to a significant reduction in the DIAPH1 mRNA and protein levels. DIAPH1-deficient T cells showed proliferation, activation, as well as TCR-mediated signaling defects. DIAPH1-deficient PBMCs also displayed impaired transwell migration, defective STAT5 phosphorylation in response to IL-2, IL-7 and IL-15. In vitro generation/expansion of Treg cells from naïve T cells was significantly reduced. shRNA-mediated silencing of DIAPH1 in Jurkat cells reduced DIAPH1 protein level and inhibited T cell proliferation and IL-2/STAT5 axis. Additionally, NK cells from patients had diminished cytotoxic activity, function and IL-2/STAT5 axis. Lastly, DIAPH1-deficient patients' peripheral blood contained dramatically reduced numbers of all helper ILC subsets. DIAPH1 deficiency results in major functional defects in T, NK cells and helper ILCs underlining the critical role of formin DIAPH1 in the biology of those cell subsets.
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Forminas , Células Matadoras Naturais , Humanos , Forminas/genética , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Masculino , Células Jurkat , Feminino , Mutação , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Criança , Imunidade Inata , Pré-Escolar , Citocinas/metabolismo , Transdução de Sinais , Imunofenotipagem , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients' long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers.
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Sequenciamento do Exoma , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Feminino , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/imunologia , Predisposição Genética para Doença , Criança , Pré-Escolar , Mutação/genética , Testes Genéticos/métodos , Lactente , Exoma/genética , AdolescenteRESUMO
BACKGROUND: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented. METHODS: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control. RESULTS: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation. CONCLUSION: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life.
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Proteínas de Ligação a DNA , Tolerância a Radiação , Imunodeficiência Combinada Severa , Humanos , Tolerância a Radiação/genética , Masculino , Feminino , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/terapia , Lactente , Proteínas de Ligação a DNA/genética , Pré-Escolar , Estudos Retrospectivos , Endonucleases/genética , Proteínas Nucleares/genética , Criança , Estudos de CoortesRESUMO
BACKGROUND: Life expectancy is a significant result indicator of public health and sustainable development. Therefore, one of the final objectives of all economic and social policies is to increase the life expectancy. In this context, a limited number of researchers have investigated the relationship between ICT penetration and life expectancy. However, multiple interaction channels exist between ICT penetration and life expectancy. Furthermore, the studies have usually focused on the effect of ICT penetration on life expectancy through regression and ignored the effect of life expectancy on ICT penetration to a large extent. Therefore, this study aims to contribute to the empirical literature by investigating the causal relationship between ICT indicators and life expectancy. METHODS: This study uses symmetric and asymmetric causality approaches to investigate the two-way interaction between ICT indicators and life expectancy in emerging market economies over the 1997-2020 period. Employment of the asymmetric causality test enables us to analyze the hidden relationships between ICT indicators and life expectancy, unlike the traditional causality test. RESULTS: The results of the symmetric causality test uncover a bidirectional causal interaction between mobile subscriptions and life expectancy but a one-way causal relationship from life expectancy to internet usage. However, the asymmetric causality test results uncover a unidirectional causal relationship between mobile subscriptions and life expectancy in China, Colombia, Czechia, Egypt, Greece, India, Kuwait and Turkiye due to positive shocks from mobile subscriptions. On the other hand, a bidirectional causal interaction exists between internet usage and life expectancy in all countries due to negative shocks from internet usage and life expectancy. Last, a unidirectional causal relationship exists between internet usage and life expectancy in all countries due to positive shocks from internet usage. CONCLUSION: ICT indicators significantly influence life expectancy health in a sample of emerging market economies. Therefore, internet usage and mobile devices are significant tools to improve life expectancy.
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Desenvolvimento Econômico , Expectativa de Vida , Humanos , Investimentos em Saúde , China , ÍndiaRESUMO
PURPOSE: Immunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive combined immunodeficiency. The detailed immune responses are not explored widely. We investigated known and novel immune alterations in lymphocyte subpopulations and their association with clinical symptoms in a well-defined ICF cohort. METHODS: We recruited the clinical findings from twelve ICF1 and ICF2 patients. We performed detailed immunological evaluation, including lymphocyte subset analyses, upregulation, and proliferation of T cells. We also determined the frequency of circulating T follicular helper (cTFH) and regulatory T (Treg) cells and their subtypes by flow cytometry. RESULTS: There were ten ICF1 and two ICF2 patients. We identified two novel homozygous missense mutations in the ZBTB24 gene. Respiratory tract infections were the most common recurrent infections among the patients. Gastrointestinal system (GIS) involvements were observed in seven patients. All patients received intravenous immunoglobulin replacement therapy and antibacterial prophylaxis; two died during the follow-up period. Immunologically, CD4+ T-cell counts, percentages of recent thymic emigrant T cells, and naive CD4+ T decreased in two, five, and four patients, respectively. Impaired T-cell proliferation and reduced CD25 upregulation were detected in all patients. These changes were more prominent in CD8+ T cells. GIS involvements negatively correlated with CD3+ T-, CD3+CD4+ T-, CD16+CD56+ NK-cell counts, and CD4+/CD8+ T-cell ratios. Further, we observed expanded cTFH cells and reduced Treg and follicular regulatory T cells with a skewing to a TH2-like phenotype in all tested subpopulations. CONCLUSION: The ICF syndrome encompasses various manifestations affecting multiple end organs. Perturbed T-cell responses with increased cTFH and decreased Treg cells may provide further insight into the immune aberrations observed in ICF syndrome.
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Síndromes de Imunodeficiência , Doenças da Imunodeficiência Primária , Humanos , Linfócitos T CD8-Positivos , Mutação , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/genética , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Proteínas Repressoras/genéticaRESUMO
BACKGROUND: Ataxia telangiectasia (AT) is a genetic multisystemic disorder affecting the nervous system. Data on neurocognitive functioning in AT are limited and focused on patients at various stages of disease. Because of the genetic nature of the disorder, parents of patients may also display subtle neurological problems. This study aimed to evaluate neurocognitive functioning in patients with AT and their unaffected parents. METHODS: The study included 26 patients with AT and 41 parents among which 13 patients and 18 parents were evaluated with neurocognitive tests. Clinical and radiological data were reviewed retrospectively. Data were analyzed with descriptive statistics. RESULTS: The median ages of patients and parents were 12.5 years (interquartile range [IQR] = 9.5) and 38.0 years (IQR = 12.0), respectively. Median intelligence quotients were 62.0 (IQR = 21.3) and 82.5 (IQR = 16.8), respectively, for patients and parents. Rates of intellectual disability for patients and parents were 100.0% and 83.3%, respectively. Areas of impairment in patients in decreasing order of frequency were motor skills, visual perception/memory, visual-manual coordination, spontaneous/focused and sustained attention (100.0% for each), social judgment, as well as vocabulary and arithmetic skills (75.0% for each). Areas of impairment in unaffected parents in decreasing order of frequency were visual-manual coordination (77.8%), working memory (76.5%), and visual perception and motor skills (66.7% for each). CONCLUSION: Intellectual disabilities, visual-spatial disabilities, and reduced visual-motor coordination seem to be similar in patients with AT and their parents. These results should be replicated with larger samples from multiple centers and may form putative cognitive endophenotypes for the disorder.
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Ataxia Telangiectasia , Pais , Humanos , Ataxia Telangiectasia/fisiopatologia , Ataxia Telangiectasia/complicações , Ataxia Telangiectasia/genética , Masculino , Feminino , Criança , Adulto , Adolescente , Estudos Retrospectivos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Testes Neuropsicológicos , Pessoa de Meia-Idade , Deficiência Intelectual/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease is ultra-rare (< 100 children or young adults worldwide) and potentially fatal. The study used mixed-methods approaches to assess how pozelimab impacts the signs and symptoms of CHAPLE disease from the patient perspective by combining within-trial interviews and clinical outcome assessments (COAs) (ClinicalTrials.gov, NCT04209634). METHODS: Interviews conducted with patients/caregivers at screening and week 24 assessed the signs and symptoms of CHAPLE disease, including those which were most bothersome, and evaluated the change. Patients/caregivers and clinicians completed the COAs; interview data contextualized the meaningfulness of change. RESULTS: Ten patients (aged 3-19 years) were enrolled; caregivers contributed to nine interviews. Abdominal pain, diarrhea, facial and peripheral edema, nausea, and vomiting are the core signs and symptoms of CHAPLE disease (≥ 90% patients experienced pre-treatment); the most bothersome signs and symptoms were abdominal pain (n = 9) and facial edema (n = 1). All core signs and symptoms were reported as resolved at week 24 interviews. Severity on global assessments changed from "mild" to "very severe" at baseline to "no signs or symptoms" at week 24. Interview results were generally consistent with sign- or symptom-specific COA scores. CONCLUSIONS: Patients with CHAPLE disease treated with pozelimab for 24 weeks experienced complete resolution of core signs and symptoms. Mixed-methods approaches can contextualize the patient experience (how patients feel and function) in rare disease trials. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04209634, registered December 24, 2019, https://classic. CLINICALTRIALS: gov/ct2/show/NCT04209634 .
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Anticorpos Monoclonais Humanizados , Humanos , Feminino , Masculino , Adolescente , Pré-Escolar , Criança , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto Jovem , Adulto , Avaliação de Resultados em Cuidados de SaúdeRESUMO
THOC6 variants are the genetic basis of autosomal recessive THOC6 Intellectual Disability Syndrome (TIDS). THOC6 is critical for mammalian Transcription Export complex (TREX) tetramer formation, which is composed of four six-subunit THO monomers. The TREX tetramer facilitates mammalian RNA processing, in addition to the nuclear mRNA export functions of the TREX dimer conserved through yeast. Human and mouse TIDS model systems revealed novel THOC6-dependent, species-specific TREX tetramer functions. Germline biallelic Thoc6 loss-of-function (LOF) variants result in mouse embryonic lethality. Biallelic THOC6 LOF variants reduce the binding affinity of ALYREF to THOC5 without affecting the protein expression of TREX members, implicating impaired TREX tetramer formation. Defects in RNA nuclear export functions were not detected in biallelic THOC6 LOF human neural cells. Instead, mis-splicing was detected in human and mouse neural tissue, revealing novel THOC6-mediated TREX coordination of mRNA processing. We demonstrate that THOC6 is required for key signaling pathways known to regulate the transition from proliferative to neurogenic divisions during human corticogenesis. Together, these findings implicate altered RNA processing in the developmental biology of TIDS neuropathology.
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Deficiência Intelectual , RNA , Estilbenos , Ácidos Sulfônicos , Humanos , Animais , Camundongos , RNA/metabolismo , Deficiência Intelectual/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Processamento Pós-Transcricional do RNA , Transporte de RNA , Mamíferos/genética , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
BACKGROUND: Major Histocompatibility Complex Class II (MHC-II) deficiency, a combined immunodeficiency, results from loss of Human Leukocyte Antigen class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation (HSCT) stands as the sole curative approach, though factors influencing patient outcomes remain insufficiently explored. OBJECTIVE: Our aim was to elucidate the clinical, immunological, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates. METHODS: In this multicenter retrospective analysis, we gathered data from 35 patients diagnosed with MHC-II deficiency across 12 centers in Turkey. We recorded infection histories, gene mutations, immune cell subsets, and surface MHC-II expression on blood cells. We conducted survival analyses to evaluate the impact of various factors on patient outcomes. RESULTS: Predominant symptoms observed were pneumonia (n=29, 82.9%), persistent diarrhea (n=26, 74.3%), and severe infections (n=26, 74.3%). The RFXANK gene mutation (n=9) was the most frequent, followed by mutations in RFX5 (n=8), CIITA (n=4), and RFXAP (n=2) genes. Patients with RFXANK mutations presented with later onset and diagnosis compared to those with RFX5 mutations (p=0.0008 and p=0.0006, respectively), alongside a more significant diagnostic delay (p=0.020). A notable founder effect was observed in 5 patients with a specific RFX5 mutation (c.616G>C). The overall survival rate for patients was 28.6% (n=10), showing a significantly higher proportion in individuals with HSCT (n=8, 80%). Early demise (p=0.006) and higher CD8+ T-cell counts were observed in patients with the RFX5 mutations compared to RFXANK-mutant patients (p=0.006 and p=0.009, respectively). CONCLUSION: The study delineates the genetic and clinical panorama of MHC-II deficiency, emphasizing the prevalence of specific gene mutations such as RFXANK and RFX5. These insights facilitate early diagnosis and prognosis refinement, significantly contributing to the management of MHC-II deficiency.
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BACKGROUND: The prevalence of allergic disorders is on the rise, affecting about 10% of the population. In this retrospective cohort, we investigated prevalence of allergic disorders, associated risk factors, and the outcome of food allergies. MATERIAL AND METHODS: We analyzed data from birth cohorts of two university hospitals' well-child outpatient clinics. Factors related to onset and type of allergic diseases were assessed from demographic, socioeconomic, and clinical data. RESULTS: Analyses were performed on 949 (431F/518M) infants at a mean current age of 28 ± 6 months. Any allergic disease was established among 177 cases (22%); atopic dermatitis in 123 (12.8%), respiratory allergies in 55 (5.7%), and food allergy in 41 (4.3%). The risk for allergic disorders was found to be significantly increased for male gender (OR: 2.31, 95% CI; 1.54-3.46), and positive parental atopy (OR: 1.94, 95% CI; 1.31-2.86). The risk of food allergies was significantly higher in the male gender (OR: 2.47, 95% CI; 1.21-5.02), who consumed egg-white between 6 and 12 months (OR: 2.34, 95% CI; 1.22-4.48), and who were formula-fed before 6 months (OR: 2.16, 95% CI; 1.14-4.10). We found no significant association between the rate of food allergy outgrowth or food induced-anaphylaxis with regards to the timing of introducing egg-white into the diet. CONCLUSIONS: Although the introduction of egg-white into infant diet at 6-12 months of life appeared as an independent risk for any food allergy, none of the patients developed anaphylaxis. Age at symptom onset and outgrowing food allergy were similar compared to those introduced egg-white after 12 months. We recommend promoting exclusive breastfeeding during the first 6 months of life, and avoidance of prolonged restrictive diets for children with food allergy
No disponible
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Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Hipersensibilidade a Ovo/epidemiologia , Hipersensibilidade Alimentar/epidemiologia , Fatores de Risco , Turquia/epidemiologia , Estudos Retrospectivos , Dermatite Atópica/epidemiologia , Dermatite Atópica/terapia , Modelos LogísticosRESUMO
No disponible