Our large multicenter study identified the finding that the initial appearance of childhood-onset SLE is characterized by comparable high frequency of internal organ involvement and some distinct clinical and laboratory features in early-onset and adolescent groups.

BackgroundCanakinumab is a human anti-interleukin-1β (IL-1β) monoclonal antibody neutralizing IL-1β-mediated pathways. We sought to characterize the molecular response to canakinumab and evaluate potential markers of response using samples from two pivotal trials in systemic juvenile idiopathic arthritis (SJIA).MethodsGene expression was measured in patients with febrile SJIA and in matched healthy controls by Affymetrix DNA microarrays. Transcriptional response was assessed by gene expression changes from baseline to day 3 using adapted JIA American College of Rheumatology (aACR) response criteria (50 aACR JIA). Changes in pro-inflammatory cytokines IL-6 and IL-18 were assessed up to day 197.ResultsMicroarray analysis identified 984 probe sets differentially expressed (≥2-fold difference; P < 0.05) in patients versus controls. Over 50% of patients with ≥50 aACR JIA were recognizable by baseline expression values. Analysis of gene expression profiles from patients achieving ≥50 aACR JIA response at day 15 identified 102 probe sets differentially expressed upon treatment (≥2-fold difference; P < 0.05) on day 3 versus baseline, including IL-1β, IL-1 receptors (IL1-R1 and IL1-R2), IL-1 receptor accessory protein (IL1-RAP), and IL-6. The strongest clinical response was observed in patients with higher baseline expression of dysregulated genes and a strong transcriptional response on day 3. IL-6 declined by day 3 (≥8-fold decline; P < 0.0001) and remained suppressed. IL-18 declined on day 57 (≥1.5-fold decline, P ≤ 0.002).ConclusionsTreatment with canakinumab in SJIA patients resulted in downregulation of innate immune response genes and reductions in IL-6 and clinical symptoms. Additional research is needed to investigate potential differences in the disease mechanisms in patients with heterogeneous gene transcription profiles.Trial registrationClinicaltrials.gov: NCT00886769 (trial 1). Registered on 22 April 2009; NCT00889863 (trial 2). Registered on 21 April 2009.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1212-x) contains supplementary material, which is available to authorized users.

Background: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. Objective: We sought to investigate the incidence of gene mosaicism in patients with PIDs. Methods: The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n 5 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n 5 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n 5 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. Results: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderateto-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. Conclusion: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs.

We evaluated the prevalence and clinical associations of amenorrhea in 298 female juvenile systemic lupus erythematosus (JSLE) patients (ACR criteria) followed in 12 Brazilian Paediatric Rheumatology centres. Amenorrhea was observed in 35 patients (11.7%) with a mean duration of 7.2 +/- 3.6 months. The hormones were performed in 32/35 patients and none of them had FSH and LH levels above and estradiol below the normal range according to pubertal changes. JSLE patients with amenorrhea were younger (15.04 +/- 2.5 versus 17.8 +/- 3.1 years; P = 0.001), and had a shorter period of time between menarche and current age (3.4 +/- 2.9 versus 6.7 +/- 5.4 years; P = 0.001). Interestingly, the frequency, cumulative dose, number of pulses and duration of intravenous cyclophosphamide treatment were alike in patients with and without amenorrhea (P > 0.05). In contrast, patients with amenorrhea had significantly higher SLEDAI (P = 0.01) and SLICC/ACR-DI (P = 0.024) scores compared to those without this condition. Independent risk factors identified by multivariate analysis were higher SLEDAI (OR = 1.059; CI = 1.004-1.116; P = 0.034) and SLICC/ACR-DI (OR = 2.125; IC = 1.373-3.291; P = 0.001) scores. Our data suggest that in spite of immunosuppressive therapy, JSLE patients have an adequate ovarian follicular reserve and amenorrhea is particularly associated with disease activity and damage.

Objective: There are several factors that contribute to poor adherence to treatment in children and adolescents with chronic rheumatic diseases, worsening their quality of life and prognosis. Our aim was to assess the rates of adherence to treatment and to identify the socioeconomic and clinical factors associated. Methods:The sample included 99 patients with juvenile idiopathic arthritis, systemic erythematosus lupus, dermatomyositis or juvenile scleroderma. All patients were followed at the outpatient pediatric rheumatology for a minimum period of 6 months. To assess adherence, a questionnaire was administered to the providers, which included three blocks: 1) demographic, clinical and laboratory data; 2) medication adherence; and 3) attending follow-up appointments, examinations and use of orthoses. A value lower than or equal to 80% of the prescribed was considered poor adherence.Results: A total of 53% of patients showed good overall adherence, observed when the caregiver lived in a stable union marital status (p = 0.006); 20 patients (20.2%) presented poor medication adherence, related to the use of three or more medications daily (p = 0.047). The causes of poor adherence were forgetfulness, refusal, incorrect dose or lack of medication, personal problems, and financial difficulties. Conclusions:We observed good overall treatment adherence in patients whose providers lived in stable union and poor adherence to medication in patients who used more than three types of medication daily. There was no association between the adherence rates and sex, age, time since diagnosis and disease activity. J Pediatr (Rio J). 2012;88(6):483-8:Patient adherence, therapy, chronic disease, pediatrics, rheumatology. ResumoObjetivo: São vários os fatores que contribuem para a má adesão ao tratamento de crianças e adolescentes com doenças reumáticas crônicas, gerando piora da qualidade de vida e do prognóstico. Nosso objetivo foi avaliar as taxas de adesão ao tratamento e identificar os fatores socioeconômicos e clínicos associados. Métodos:Foram incluídos 99 pacientes com artrite idiopática juvenil, lúpus eritematoso sistêmico, dermatomiosite ou esclerodermia juvenil. Todos os pacientes eram acompanhados no ambulatório de reumatologia pediátrica por um período mínimo de 6 meses. Para avaliação da adesão, foi aplicado aos cuidadores um questionário composto por três blocos: 1) dados demográficos, clínicos e laboratoriais; 2) adesão ao tratamento medicamentoso; e 3) comparecimento às consultas, realização de exames e utilização de órteses. Foi considerada má adesão, quando realizado valor menor ou igual a 80% do prescrito.Resultados: Um total de 53% dos pacientes apresentou boa adesão ao tratamento global, observada quando o cuidador possuía união estável (p = 0,006); 20 pacientes (20,2%) apresentaram má adesão ao tratamento medicamentoso, relacionada à utilização de mais que três medicamentos diários (p = 0,047). As causas de má adesão ao tratamento foram esquecimento, recusa, dose incorreta ou falta de medicamento, prob...