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INTRODUCTION: Activation of the focal adhesion kinase (FAK) in podocytes is involved in the pathogenesis of minimal change disease (MCD), but the pathway leading to its activation in this disease is unknown. Here, we tested whether podocyte ß1 integrin is the upstream modulator of FAK activation and podocyte injury in experimental models of MCD-like injury. METHODS: We used lipopolysaccharide (LPS) and MCD sera to induce MCD-like changes in vivo and in cultured human podocytes, respectively. We performed functional studies using specific ß1 integrin inhibitors in vivo and in vitro, and integrated histological analysis, western blotting, and immunofluorescence to assess for morphological and molecular changes in podocytes. By ELISA, we measured serum LPS levels in 35 children with MCD or presumed MCD (idiopathic nephrotic syndrome [INS]) and in 18 healthy controls. RESULTS: LPS-injected mice showed morphological (foot process effacement, and normal appearing glomeruli on light microscopy) and molecular features (synaptopodin loss, nephrin mislocalization, FAK phosphorylation) characteristic of human MCD. Administration of a ß1 integrin inhibitor to mice abrogated FAK phosphorylation, and ameliorated proteinuria and podocyte injury following LPS. Children with MCD/INS in relapse had higher serum LPS levels than controls. In cultured human podocytes, ß1 integrin blockade prevented cytoskeletal rearrangements following exposure to MCD sera in relapse. CONCLUSIONS: Podocyte ß1 integrin activation is an upstream mediator of FAK phosphorylation and podocyte injury in models of MCD-like injury.
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Nefrose Lipoide , Síndrome Nefrótica , Podócitos , Criança , Camundongos , Humanos , Animais , Nefrose Lipoide/induzido quimicamente , Integrina beta1/metabolismo , Lipopolissacarídeos/metabolismo , Modelos Teóricos , RecidivaRESUMO
Autosomal dominant loss-of-function (LoF) variants in cytotoxic T-lymphocyte associated protein 4 (CTLA4) cause immune dysregulation with autoimmunity, immunodeficiency and lymphoproliferation (IDAIL). Incomplete penetrance and variable expressivity are characteristic of IDAIL caused by CTLA-4 haploinsufficiency (CTLA-4h), pointing to a role for genetic modifiers. Here, we describe an IDAIL proband carrying a maternally inherited pathogenic CTLA4 variant and a paternally inherited rare LoF missense variant in CLEC7A, which encodes for the ß-glucan pattern recognition receptor DECTIN-1. The CLEC7A variant led to a loss of DECTIN-1 dimerization and surface expression. Notably, DECTIN-1 stimulation promoted human and mouse regulatory T cell (Treg) differentiation from naïve αß and γδ T cells, even in the absence of transforming growth factor-ß. Consistent with DECTIN-1's Treg-boosting ability, partial DECTIN-1 deficiency exacerbated the Treg defect conferred by CTL4-4h. DECTIN-1/CLEC7A emerges as a modifier gene in CTLA-4h, increasing expressivity of CTLA4 variants and acting in functional epistasis with CTLA-4 to maintain immune homeostasis and tolerance.
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Haploinsuficiência , Lectinas Tipo C , Animais , Humanos , Camundongos , Autoimunidade , Antígeno CTLA-4/genética , Lectinas Tipo C/genéticaRESUMO
PURPOSE: To determine whether hypercapnia is associated with risk of hospital readmission related to anorexia nervosa (AN) in children and adolescents. METHODS: We performed a prospective study of patients ≤ 18 years old admitted due to AN decompensation from November 2018 to October 2019. Both subtypes of AN, restricting subtype (AN-R) and binge-eating/purging subtype (AN-BP), were included. Study participants were evaluated upon admission, at discharge and six months after discharge. T-tests or Mann-Whitney U tests was used to compare means values. Pearson or Spearman correlations were used to measure the association between two variables. Logistic regression models were developed to evaluate the relationship between scoring methods and readmission. RESULTS: Of the 154 persons admitted during the study period, 131 met the inclusion criteria. Median age was 15.1 years. At admission, 71% of participants were malnourished and 33 (25%) had been previously admitted. We observed a marked decrease in venous pH and stable pCO2 elevation during follow-up period. Hypercapnia at discharge was associated with a twofold increased likelihood of readmission and the odds of readmission increased as discharge pCO2 rose. These findings did not depend on AN subtype or participant sex. Electrolytes persisted within the normal range. CONCLUSION: Hypercapnia and respiratory acidosis are common alterations in children and adolescents hospitalized due to AN decompensation. Hypercapnia persists for at least 6 months after discharge despite clinical improvement and is associated with higher odds of readmission. This is the first study to identify an abnormal laboratory finding as a potential predictor of readmission in AN. LEVEL OF EVIDENCE: IV: Multiple time series without intervention.
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Anorexia Nervosa , Criança , Humanos , Adolescente , Anorexia Nervosa/complicações , Estudos Prospectivos , Criança Hospitalizada , Hipercapnia/complicações , Readmissão do PacienteRESUMO
BACKGROUND: X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive, renal phosphate-wasting disorder characterized by a pathological increase in FGF23 concentration and activity. Due to its rarity, diagnosis may be delayed, which can adversely affect outcomes. As a chronic disease resulting in progressive accumulation of musculoskeletal manifestations, it is important to understand the natural history of XLH over the patient's lifetime and the impact of drug treatments and other interventions. This multicentre, international patient registry (International XLH Registry) was established to address the paucity of these data. Here we present the findings of the first interim analysis of the registry. RESULTS: The International XLH Registry was initiated in August 2017 and includes participants of all ages diagnosed with XLH, regardless of their treatment and management. At the database lock for this first interim analysis (29 March 2021), 579 participants had entered the registry before 30 November 2020 and are included in the analysis (360 children [62.2%], 217 adults [37.5%] and 2 whose ages were not recorded [0.3%]; 64.2% were female). Family history data were available for 319/345 (92.5%) children and 145/187 (77.5%) adults; 62.1% had biological parents affected by XLH. Genetic testing data were available for 341 (94.7%) children and 203 (93.5%) adults; 370/546 (67.8%) had genetic test results; 331/370 (89.5%) had a confirmed PHEX mutation. A notably longer time to diagnosis was observed in adults ≥ 50 years of age (mean [median] duration 9.4 [2.0] years) versus all adults (3.7 [0.1] years) and children (1.0 [0.2] years). Participants presented with normal weight, shorter length or height and elevated body mass index (approximately - 2 and + 2 Z-scores, respectively) versus the general population. Clinical histories were collected for 349 participants (239 children and 110 adults). General data trends for prevalence of bone, dental, renal and joint conditions in all participants were aligned with expectations for a typical population of people with XLH. CONCLUSION: The data collected within the International XLH Registry, the largest XLH registry to date, provide substantial information to address the paucity of natural history data, starting with demographic, family history, genetic testing, diagnosis, auxology and baseline data on clinical presentation.
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Raquitismo Hipofosfatêmico Familiar , Doenças Genéticas Ligadas ao Cromossomo X , Criança , Adulto , Humanos , Feminino , Pré-Escolar , Masculino , Raquitismo Hipofosfatêmico Familiar/genética , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação , Sistema de Registros , DemografiaAssuntos
Hiperuricemia , Doenças Renais Policísticas , Humanos , Hiperuricemia/genética , Mutação , Uromodulina/genéticaRESUMO
Background: X-linked hypophosphataemia (XLH) is a rare, inherited, phosphate-wasting disorder that elevates fibroblast growth factor 23 (FGF23), causing renal phosphate-wasting and impaired active vitamin D (1,25(OH)2D) synthesis. Disease characteristics include rickets, osteomalacia, odontomalacia, and short stature. Historically, treatment has been oral phosphate and 1,25(OH)2D supplements. However, these treatments do not correct the primary pathogenic mechanism or treat all symptoms and can be associated with adverse effects. Burosumab is a recombinant human immunoglobulin G1 monoclonal antibody against FGF23, approved for treating XLH in several geographical regions, including Europe and Israel. Burosumab restores normal serum phosphate levels, minimising the clinical consequences of XLH. Safety data on long-term treatment with burosumab are lacking owing to the rarity of XLH. This post-authorisation safety study (PASS) aims to evaluate the safety outcomes in patients aged >1 year. Methods: The PASS is a 10-year retrospective and prospective cohort study utilising data from the International XLH Registry (NCT03193476), which includes standard diagnostic and monitoring practice data at participating centres. The PASS aims to evaluate frequency and severity of safety outcomes, frequency and outcomes of pregnancies in female patients, and safety outcomes in patients with mild to moderate kidney disease at baseline, in children, adolescents and adults treated with burosumab for XLH. It is expected that there will be at least 400 patients who will be administered burosumab. Results: Data collection started on 24 April 2019. The expected date of the final study report is 31 December 2028, with two interim reports. Conclusion: This PASS will provide data on the long-term safety of burosumab treatment for XLH patients and describe safety outcomes for patients receiving burosumab contrasted with those patients receiving other XLH treatments, to help inform the future management of XLH patients. The PASS will be the largest real-world safety study of burosumab. Registry identification: The International XLH Registry is registered with clinicaltrials.gov as NCT03193476 (https://clinicaltrials.gov/ct2/show/NCT03193476), and the PASS is registered with the European Union electronic Register of Post-Authorisation Studies as EUPAS32190 (http://www.encepp.eu/encepp/viewResource.htm?id=32191).
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Introduction: Minimal change disease (MCD) is considered a podocyte disorder triggered by unknown circulating factors. Here, we hypothesized that the endothelial cell (EC) is also involved in MCD. Methods: We studied 45 children with idiopathic nephrotic syndrome (44 had steroid sensitive nephrotic syndrome [SSNS], and 12 had biopsy-proven MCD), 21 adults with MCD, and 38 healthy controls (30 children, 8 adults). In circulation, we measured products of endothelial glycocalyx (EG) degradation (syndecan-1, heparan sulfate [HS] fragments), HS proteoglycan cleaving enzymes (matrix metalloprotease-2 [MMP-2], heparanase activity), and markers of endothelial activation (von Willebrand factor [vWF], thrombomodulin) by enzyme-linked immunosorbent assay (ELISA) and mass spectrometry. In human kidney tissue, we assessed glomerular EC (GEnC) activation by immunofluorescence of caveolin-1 (n = 11 MCD, n = 5 controls). In vitro, we cultured immortalized human GEnC with sera from control subjects and patients with MCD/SSNS sera in relapse (n = 5 per group) and performed Western blotting of thrombomodulin of cell lysates as surrogate marker of endothelial activation. Results: In circulation, median concentrations of all endothelial markers were higher in patients with active disease compared with controls and remained high in some patients during remission. In the MCD glomerulus, caveolin-1 expression was higher, in an endothelial-specific pattern, compared with controls. In cultured human GEnC, sera from children with MCD/SSNS in relapse increased thrombomodulin expression compared with control sera. Conclusion: Our data show that alterations involving the systemic and glomerular endothelium are nearly universal in patients with MCD and SSNS, and that GEnC can be directly activated by circulating factors present in the MCD/SSNS sera during relapse.
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BACKGROUND: Fanconi syndrome (FS) can be of primary or secondary origin. Some cases of FS secondary to the use of sodium valproate (VPA) have been described, mostly in children with severe psychomotor retardation who are fed by feeding device. The objetive of this study was to describe patients treated for this entity in our center, comparing them against the published literature. METHODS: Descriptive study of our patients and those found in the literature. Epidemiologic and clinical data were collected. RESULTS: We describe seven patients (three to 17 years old) with severe psychomotor retardation and undergoing treatment with VPA. Four presented pathologic fractures before the diagnosis of FS, and in three patients the diagnosis was reached due to abnormal laboratory findings. A review of the published cases was carried out and, including our sample, a total of 42 patients were studied: 51.3% were male, and the median age at diagnosis of FS was 6 years. Severe psychomotor retardation was found in 92.8% of patients, 78% carried a feeding device, and 77.5% received treatment with several antiepileptic drugs. The mean duration of VPA treatment was 5.7 years (range 2 to 7.5 years). Fifteen patients (37.5%) had bone complications. The resolution time of FS after discontinuation of drug therapy ranged from two to 19 months (median 4 months). CONCLUSIONS: FS related to VPA is a rare complication, but it should be considered in patients with epilepsy, especially if they have severe psychomotor retardation, are users of feeding devices, and receive other antiepileptic treatments in addition to VPA.
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Epilepsia , Síndrome de Fanconi , Adolescente , Anticonvulsivantes/efeitos adversos , Criança , Pré-Escolar , Epilepsia/tratamento farmacológico , Síndrome de Fanconi/induzido quimicamente , Síndrome de Fanconi/tratamento farmacológico , Feminino , Humanos , Masculino , Ácido Valproico/efeitos adversosRESUMO
Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease1-7, evidence of lupus-causing TLR7 gene variants is lacking. Here we describe human systemic lupus erythematosus caused by a TLR7 gain-of-function variant. TLR7 is a sensor of viral RNA8,9 and binds to guanosine10-12. We identified a de novo, previously undescribed missense TLR7Y264H variant in a child with severe lupus and additional variants in other patients with lupus. The TLR7Y264H variant selectively increased sensing of guanosine and 2',3'-cGMP10-12, and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c+ age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7Y264H mice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.
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Mutação com Ganho de Função , Lúpus Eritematoso Sistêmico , Receptor 7 Toll-Like , Animais , Autoimunidade/genética , Linfócitos B , GMP Cíclico/análogos & derivados , Guanosina , Humanos , Lúpus Eritematoso Sistêmico/genética , Camundongos , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismoRESUMO
Given the relatively recent introduction of burosumab in the management of X-linked hypophosphatemia (XLH), there is limited real-world data to guide its use in clinical practice. As a group of European physicians experienced with burosumab treatment in clinical practice, we convened with the objective of sharing these practice-based insights on the use of burosumab in children and adolescents with XLH. We attended two virtual meetings, then discussed key questions via Within3, a virtual online platform. Points of discussion related to patient selection criteria, burosumab starting dose, dose titration and treatment monitoring. Our discussions revealed that criteria for selecting children with XLH varied across Europe from all children above 1 year to only children with overt rickets despite conventional treatment being eligible. We initiated burosumab dosing according to guidance in the Summary of Product Characteristics, an international consensus statement from 2019 and local country guidelines. Dose titration was primarily guided by serum phosphate levels, with some centers also using the ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate (TmP/GFR). We monitored response to burosumab treatment clinically (growth, deformities, bone pain and physical functioning), radiologically (rickets and deformities) and biochemically (serum phosphate, alkaline phosphatase, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, urine calcium-creatinine ratio and TmP/GFR). Key suggestions made by our group were initiation of burosumab treatment in children as early as possible, from the age of 1 year, particularly in those with profound rickets, and a need for clinical studies on continuation of burosumab throughout adolescence and into adulthood.
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Raquitismo Hipofosfatêmico Familiar , Humanos , Criança , Adolescente , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Europa (Continente) , FosfatosRESUMO
INTRODUCTION: Lupus nephritis is an early manifestation in the development of systemic lupus erythematosus that worsens the morbidity and mortality of these patients. OBJECTIVE: To study the form of presentation in patients with lupus nephritis, the clinical and immunological characteristics, and their relationship with renal histology. PATIENTS AND METHOD: Retrospective study in children under 18 years of age, with lupus nephritis, in follow-up in a third level children's hospital in Madrid, between January 2012 and May 2020. We recorded demographic, clinical, and laboratory data (blood count, renal function, liver function, protein, ionogram, blood glucose, uric acid, lactate dehydrogenase, coagulation, and urine analysis), as well as immunological data (immunoglobulins, antinuclear antibodies, comple ment, and lupus anticoagulant), and histological classification data. Descriptive analysis and analysis of associations between variables was performed, with a significant p < 0.05. RESULTS: 16 patients (11 women) were included, the median age at presentation was 10.6 ± 2.3 years (5.7-15.3). The median time between symptoms onset and renal involvement was 6.3 months ± 10.5 (range 0 - 33.6). Renal involvement was the initial manifestation in 37.5% of patients. 50% had arthralgias or arthritis prior to diagnosis, and 25% had fever and constitutional symptoms (asthenia, anorexia, and/or weight loss). The most frequent form of renal involvement was microhematuria associated with proteinuria in non-nephrotic range. In the renal anatomo-pathological study, according to the ISN/RPS 2003 classification, grades III (46.6%) and IV (33.3%) predominated. CONCLUSIONS: Six patients presented renal involvement at baseline with musculoskeletal involvement being more frequent. Most patients (86.6%) presented advanced lupus nephritis in the histological study at diagnosis. Immunologic in volvement was the only marker that correlated with systemic involvement.
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Rim/patologia , Nefrite Lúpica/diagnóstico , Adolescente , Biomarcadores/metabolismo , Biópsia , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Rim/imunologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Nefrite Lúpica/terapia , Masculino , Estudos Retrospectivos , Tempo para o TratamentoRESUMO
BACKGROUND: X-linked hypophosphatemia (XLH) is a hereditary rare disease caused by loss-of-function mutations in PHEX gene leading tohypophosphatemia and high renal loss of phosphate. Rickets and growth retardation are the major manifestations of XLH in children, but there is a broad phenotypic variability. Few publications have reported large series of patients. Current data on the clinical spectrum of the disease, the correlation with the underlying gene mutations, and the long-term outcome of patients on conventional treatment are needed, particularly because of the recent availability of new specific medications to treat XLH. RESULTS: The RenalTube database was used to retrospectively analyze 48 Spanish patients (15 men) from 39 different families, ranging from 3 months to 8 years and 2 months of age at the time of diagnosis (median age of 2.0 years), and with XLH confirmed by genetic analysis. Bone deformities, radiological signs of active rickets and growth retardation were the most common findings at diagnosis. Mean (± SEM) height was - 1.89 ± 0.19 SDS and 55% (22/40) of patients had height SDS below-2. All cases had hypophosphatemia, serum phosphate being - 2.81 ± 0.11 SDS. Clinical manifestations and severity of the disease were similar in both genders. No genotype-phenotype correlation was found. Conventional treatment did not attenuate growth retardation after a median follow up of 7.42 years (IQR = 11.26; n = 26 patients) and failed to normalize serum concentrations of phosphate. Eleven patients had mild hyperparathyroidism and 8 patients nephrocalcinosis. CONCLUSIONS: This study shows that growth retardation and rickets were the most prevalent clinical manifestations at diagnosis in a large series of Spanish pediatric patients with XLH confirmed by mutations in the PHEX gene. Traditional treatment with phosphate and vitamin D supplements did not improve height or corrected hypophosphatemia and was associated with a risk of hyperparathyroidism and nephrocalcinosis. The severity of the disease was similar in males and females.
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Raquitismo Hipofosfatêmico Familiar , Doenças Genéticas Ligadas ao Cromossomo X , Hipofosfatemia , Criança , Pré-Escolar , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Raquitismo Hipofosfatêmico Familiar/genética , Feminino , Humanos , Masculino , Mutação/genética , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Estudos RetrospectivosRESUMO
Minimal change disease (MCD) is the most common type of idiopathic nephrotic syndrome in childhood and represents about 15% cases in adults. It is characterized by massive proteinuria, edema, hypoalbuminemia, and podocyte foot process effacement on electron microscopy. Clinical and experimental studies have shown an association between MCD and immune dysregulation. Given the lack of inflammatory changes or immunocomplex deposits in the kidney tissue, MCD has been traditionally thought to be mediated by an unknown circulating factor(s), probably released by T cells that directly target podocytes leading to podocyte ultrastructural changes and proteinuria. Not surprisingly, research efforts have focused on the role of T cells and podocytes in the disease process. Nevertheless, the pathogenesis of the disease remains a mystery. More recently, B cells have been postulated as an important player in the disease either by activating T cells or by releasing circulating autoantibodies against podocyte targets. There are also few reports of endothelial injury in MCD, but whether glomerular endothelial cells play a role in the disease remains unexplored. Genome-wide association studies are providing insights into the genetic susceptibility to develop the disease and found a link between MCD and certain human haplotype antigen variants. Altogether, these findings emphasize the complex interplay between the immune system, glomerular cells, and the genome, raising the possibility of distinct underlying triggers and/or mechanisms of proteinuria among patients with MCD. The heterogeneity of the disease and the lack of good animal models of MCD remain major obstacles in the understanding of MCD. In this study, we will review the most relevant candidate mediators and mechanisms of proteinuria involved in MCD and the current models of MCD-like injury.
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Thrombotic thrombocytopaenic purpura (TTP) is a life-threatening thrombotic microangiopathy characterised by microangiopathic haemolytic anaemia, thrombocytopaenia and organ ischaemia. TTP is caused by a severe functional deficiency of ADAMTS13 activity. We describe a 10-year-old girl presenting anaemia and thrombocytopaenia with schistocytes. Urine protein to creatinine ratio was within nephrotic range. ADAMTS13 activity was 0%, and no anti-ADAMTS13 antibodies were found. A renal biopsy showed deposits of IgG, C3 and C1q in the capillary membrane, compatible with class V lupus nephritis. Therapeutic plasma exchange (TPE) was performed in conjunction with therapy consisting of steroids and mycophenolate mofetil. After 11 months of follow-up, the patient remains in remission with normal ADAMTS13 activity. Although acquired TTP is a rare finding in children, differential diagnosis of thrombotic microangiopathy should include ADAMTS13 and the assay should be performed early. TTP treatment is based on TPE, although the underlying disease must be ruled out to optimise treatment and prevent relapse.
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Proteína ADAMTS13/análise , Nefrite Lúpica/diagnóstico , Troca Plasmática , Púrpura Trombocitopênica Trombótica/etiologia , Proteína ADAMTS13/deficiência , Proteína ADAMTS13/genética , Biópsia , Criança , Diagnóstico Diferencial , Feminino , Glucocorticoides/uso terapêutico , Humanos , Rim/patologia , Nefrite Lúpica/sangue , Nefrite Lúpica/complicações , Nefrite Lúpica/terapia , Ácido Micofenólico/uso terapêutico , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Análise de Sequência de DNA , Resultado do TratamentoRESUMO
Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Proteínas de Membrana/genética , Quinases da Família src/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Animais , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Núcleo Celular/imunologia , Núcleo Celular/metabolismo , Criança , Modelos Animais de Doenças , Feminino , Frequência do Gene , Células HEK293 , Voluntários Saudáveis , Humanos , Fatores Reguladores de Interferon/imunologia , Fatores Reguladores de Interferon/metabolismo , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação de Sentido Incorreto , Sequenciamento do Exoma , Quinases da Família src/metabolismoRESUMO
BACKGROUND & AIMS: Iodine deficiency inhibits the normal development of human beings and is the leading cause of preventable mental retardation. Our study aims to update the urinary iodine concentrations and the intake of iodized salt in children in Madrid (Spain). METHODS: A cross-sectional study was designed where 217 children aged 3-14 years old were studied. A nutritional survey including the intake of iodized salt and other iodine-rich foods was performed. In addition, the urinary concentration of iodine was determined in each patient. RESULTS: Near 60% of the surveyed households routinely used iodized salt. Significant differences in age, sex, country of birth, or country of birth and parents educational levels and iodized salt consumption were not found. The median of the urinary iodine level (120 µg/L; interquartile range 80-184) was significantly higher in boys than girls and more elevated in younger children. Iodized salt and milk consumption significantly increased the concentration of urinary iodine. Children who drank less than two glasses of milk per day and did not consume iodized salt have four times the risk of iodine deficiency compared to children who daily drank at least two glasses of milk and consumed iodized salt (P < 0.001). CONCLUSIONS: The nutritional level of iodine in the children studied is appropriate despite the low consumption of iodized salt. This is due to the consumption of dairy products and milk. The younger the child, the better his/her iodine nutritional level. Teenagers studied are at higher risk of iodine deficiency.