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  • Gene Expression Profiling and Association Studies Implicate the Neuregulin Signaling Pathway in Behçet's Disease Susceptibility
    Publication . Xavier, J; Krug, T; Davatchi, F; Shahram, F; Fonseca, B; Jesus, G; Barcelos, F; Vedes, J; Salgado, M; Abdollahi, B; Nadji, A; Moraes-Fontes, MF; Shafiee, N; Ghaderibarmi, F; Patto, J; Crespo, J; Oliveira, S
    Behçet's disease (BD) is a complex disease with genetic and environmental risk factors implicated in its etiology; however, its pathophysiology is poorly understood. To decipher BD's genetic underpinnings, we combined gene expression profiling with pathway analysis and association studies. We compared the gene expression profiles in peripheral blood mononuclear cells (PBMCs) of 15 patients and 14 matched controls using Affymetrix microarrays and found that the neuregulin signaling pathway was over-represented among the differentially expressed genes. The Epiregulin (EREG), Amphiregulin (AREG), and Neuregulin-1 (NRG1) genes of this pathway stand out as they are also among the top differentially expressed genes. Twelve haplotype tagging SNPs at the EREG-AREG locus and 15 SNPs in NRG1 found associated in at least one published BD genome-wide association study were tested for association with BD in a dataset of 976 Iranian patients and 839 controls. We found a novel association with BD for the rs6845297 SNP located downstream of EREG, and replicated three associations at NRG1 (rs4489285, rs383632, and rs1462891). Multifactor dimensionality reduction analysis indicated the existence of epistatic interactions between EREG and NRG1 variants. EREG-AREG and NRG1, which are members of the epidermal growth factor (EGF) family, seem to modulate BD susceptibility through main effects and gene–gene interactions. These association findings support a role for the EGF/ErbB signaling pathway inBD pathogenesis that warrants further investigation and highlight the importance of combining genetic and genomic approaches to dissect the genetic architecture of complex diseases.
    2013Journal article Open access Show more
  • Neuropsychiatric Questionnaires in Systemic Lupus Erythematosus
    Publication . Tani, C; Moraes-Fontes, MF; Carli, L; Mauri, M; Bombardieri, S; Mosca, M
    Patients with systemic lupus erythematosus (SLE) can be affected by a multitude of neurologic and psychiatric symptoms with a wide range of prevalence and severity. Irrespectively from attribution to SLE or other causes, neuropsychiatric (NP) symptoms strongly impact short-term and long-term outcomes,thus NP evaluation during routine clinical practice in SLE should be undertaken regularly. The assessment of NP involvement in SLE patients is challenging and the available diagnostic tools fail to guarantee optimal diagnostic accuracy, sensitivity to changes as well as feasibility in routine clinical care. Standardised questionnaires (both physician-administered and self-reported) can offer valuable help to the treating physician to capture all possible NP syndromes; few SLE-specific NP questionnaire have been developed but validation in large cohort or cross-cultural adaptations are still pending. On the other hand, general instruments have been largely applied to SLE patients. Both kinds of questionnaires can address all possible NP manifestations either globally or, more frequently, focus on specific NP symptoms. These latter have been mainly used in SLE to detect and classify mild and subtle symptoms, more likely to be overlooked during routine clinical assessment such as headache, cognitive impairment and psychiatric manifestations. In conclusion, this literature review highlights a clear case for validation studies in this area and the wider implementation of questionnaires to assess NP involvement is still warranted. The broader use of such instruments could have important consequences; first of all, by standardising symptom assessment, a better definition of the prevalence of NP manifestation across different centres could be achieved. Secondly, prospective studies could allow for the evaluation of clinical significance of mild symptoms and their impact on the patient’s function and quality of life.
    2014Journal article Open access Show more
  • IL10 Low-Frequency Variants in Behçet's Disease Patients
    Publication . Matos, M; Xavier, JM; Abrantes, P; Sousa, I; Rei, N; Davatchi, F; Shahram, F; Jesus, G; Barcelos, F; Vedes, J; Salgado, Manuel; Abdollahi, B; Nadji, A; Moraes-Fontes, MF; Shafiee, N; Ghaderibarmi, F; Vaz Patto, J; Crespo, J; Oliveira, SA
    To explain the missing heritability after the genome-wide association studies era, sequencing studies allow the identification of low-frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene (IL10) have been consistently associated with Behçet's disease (BD) and the goal of this study is to investigate the role of low-frequency IL10 variants in BD susceptibility.
    2014-04-08Journal article Open access Show more
  • Erythema Annulare Centrifugum During Rituximab Treatment for Autoimmune Haemolytic Anaemia
    Publication . Mendes-Bastos, P; Coelho-Macias, V; Moraes-Fontes, MF; Milheiro, A; Rodrigues, AM; Cardoso, J
    2014-08Journal article Open access Show more
  • Characterization of Damage in Portuguese Lupus Patients
    Publication . Moraes-Fontes, MF; Riso, N
    2015Other Open access Show more
  • Vaccination of Adult Patients with Systemic Lupus Erythematosus in Portugal
    Publication . Moraes-Fontes, MF; Antunes, AM; Gruner, H; Riso, N
    In the wake of the Portuguese vaccination program 50th anniversary it seems appropriate to review vaccination in patients with systemic lupus erythematosus. Controversial issues as regards the association between autoimmune diseases, infections, and vaccines are discussed as well as vaccine safety and efficacy issues as regards chronic immunosuppressant (IS) drug therapy. After a brief overview of national policies, specific recommendations are made as regards vaccination for adult patients with SLE with a particular focus on current IS therapy and unmet needs.
    2016Journal article Open access Show more
  • 2016-06-16Journal article Open access Show more
  • Ultrasound Detects Subclinical Joint Inflammation in the Hands and Wrists of Patients With Systemic Lupus Erythematosus Without Musculoskeletal Symptoms
    Publication . Ruano, C; Malheiro, R; Oliveira, JF; Pinheiro, S; Vieira, LS; Moraes-Fontes, MF
    OBJECTIVES: To assess the prevalence and severity of ultrasonographic abnormalities of the hand and wrist of asymptomatic patients with systemic lupus erythematosus (SLE) and compare these findings with those from patients with SLE with musculoskeletal signs or symptoms and healthy controls. METHODS: We conducted a prospective cross-sectional study that evaluated bilaterally, with grey-scale and power Doppler (PD) ultrasound (US), the dorsal hand (2nd to 5th metacarpophalangeal and 2nd to 5th proximal interphalangeal joints) and wrist (radiocarpal, ulnocarpal and intercarpal joints) of 30 asymptomatic patients with SLE, 6 symptomatic patients with SLE and 10 controls. Synovial hypertrophy (SH) and intra-articular PD signal were scored using semiquantitative grading scales (0-3). Individual scores were graded as normal (SH≤1 and PD=0) or abnormal (SH≥2 or PD≥1). Global indexes for SH and PD were also calculated. US findings were correlated with clinical and laboratory data and disease activity indexes. RESULTS: US detected SH (score ≥1) in 77% asymptomatic patients with SLE, mostly graded as minimal (score 1: 63%). 23% of the asymptomatic patients with SLE showed abnormal US PD findings (SH≥2 or PD≥1). SH was present in all symptomatic patients with SLE, mostly graded as moderate (grade 2: 67%), and with associated PD signal (83%). SH (score 1) was identified in 50% of controls, however, none presented abnormal US PD findings. SH index in the asymptomatic SLE group was higher than in the control group (2.0 (0-5) vs 0.5 (0-2), median (range), p=0.01) and lower than in the symptomatic SLE group (7.0 (4-23), median (range), p<0.001). No significant correlation was demonstrated between US PD findings and clinical or laboratory variables and disease activity indexes. CONCLUSION: A small subgroup of asymptomatic patients with SLE may present subclinical joint inflammation. Global US scores and PD signal may be important in disease evaluation and therapeutic monitoring.
    2017Journal article Open access Show more
  • Immunodeficiency and Autoimmunity Coming Together: a Nearly Missed Diagnosis
    Publication . Carreiro, F; Betkova, S; Sepúlveda, C; Manata, MJ; Cardoso, O; Maltez, F; Moraes-Fontes, MF
    The coexistence of human immunodeficiency virus (HIV) and systemic lupus erythematosus (SLE) appears to be unusual and the prevalence of patients who carry the dual diagnosis is currently unknown. We hereby present a case of a C4 deficient HIV-1 positive Caucasian female under highly active antiretroviral therapy for the past eight years, admitted to hospital with an aggressive and potentially fatal clinical presentation of SLE. There was a favorable outcome despite a significant diagnostic delay. Despite its rarity, the case highlights that this association is remarkable and may be overlooked by clinicians familiar with either condition.
    2017Journal article Open access Show more
  • Fatores Determinantes de Morbilidade nos Doentes com Lúpus Eritematoso Sistémico
    Publication . Jacinto, M; Silva, E; Riso, N; Moraes-Fontes, MF
    Introdução: O lúpus eritematoso sistémico pode apresentar uma gravidade variável. Contudo, não existem biomarcadores que preveem o curso da doença. O dano é medido pelo índice Systemic Lupus International Collaborating Clinics/Systemic Damage Index que define a gravidade e prevê o seu prognóstico. Objetivo: Avaliação dos fatores que determinam dano nos doentes com lúpus eritematoso sistémico. Material e Métodos: Estudo retrospetivo, monocêntrico, em doentes com lúpus eritematoso sistémico (≥ 4 critérios do American College of Rheumatology – 100% dos doentes, n = 76), do sexo feminino, seguidos por um período ≥ 5 anos. Início da doença, etnia, duração, número de critérios American College of Rheumatology no final do seguimento, fenótipo renal, neuropsiquiátrico (e articular, co-morbilidades e Systemic Lupus Erythematosus Disease Activity Index -2K foram correlacionados com a presença e grau de dano medido pelo índice Systemic Lupus International Collaborating Clinics/Systemic Damage Index. A acumulação de critérios American College of Rheumatology foi objetivada num sub-grupo de doentes seguidos desde o início. A análise estatística utilizou o qui-quadrado, Wilcoxon Mann-Whitney e a correlação de Spearman (p < 0,05). Resultados: O Systemic Lupus International Collaborating Clinics Index era superior a 0 em 56,5% dos doentes. Estes doentes tinham um maior tempo de doença, um maior número de critérios American College of Rheumatology e um fenótipo neuropsiquiátrico, quando comparados com doentes sem dano (p < 0,05). Verificou-se uma correlação positiva entre o valor numérico de critérios American College of Rheumatology acumulados no final do seguimento e a atividade da doença nos últimos cinco anos (Spearman rho 0,02 e p < 0,05). Não se verificaram diferenças em relação às outras variáveis. Discussão e Conclusão: A duração da doença e o número de critérios do American College of Rheumatology acumulados conseguem prever a presença de dano. A doença neuropsiquiátrica teve impacto na morbilidade dos doentes com lúpus eritematoso sistémico, identificando um subgrupo em risco.
    2017-05Journal article Open access Show more