Systematic review of infliximab-induced autoantibodies and systemic lupus erythematosus.

The present systematic review aims to discuss infliximab-induced autoantibodies and subsequent onset of systemic lupus erythematosus (SLE) through the analyses of primary reports measuring autoantibodies both before and after the administration of infliximab for the treatment of several diseases - e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohn's disease. Our literature search was performed in nine databases - PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo and LILACS, and the search query retrieved 998 primary reports, from which 24 articles were selected and further narrowed down to 14, based on our inclusion criteria. Two independent reviewers performed the article selection and a third reviewer solved discrepancies. Our inclusion criteria comprised primary reports of phase IV clinical trials with duration of at least three months. In total, 760 patients were evaluated and the most prevalent assays performed in the studies were anti-nuclear antibodies (ANA), anti-double stranded DNA antibodies (anti-dsDNA), and antibodies to saline-extracted antigens (ENA panel). Of all patients evaluated, 10 (1.3%) showed clinical signs and laboratorial evidence of infliximabinduced SLE.

Revisão sistemática da indução de autoanticorpos e lúpus eritematoso pelo infliximabe / Systematic review of infliximab-induced autoantibodies and systemic lupus erythematosus

Nesta revisão sistemática abordamos a indução de autoanticorpos e lúpus eritematoso pelo infliximabe, analisando estudos que dosaram vários autoanticorpos antes e após o uso do infliximabe em diversas doenças (artrite reumatoide, espondilite anquilosante, artrite psoriásica e doença de Crohn). Nossa busca foi realizada em nove bases de dados (Pub-Med, ScienceDirect, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo e LILACS). Foram encontradas 998 referências; 24 artigos foram separados na íntegra, dos quais 10 foram excluídos por não entrarem em nossos critérios de seleção. A escolha dos artigos foi realizada por dois revisores, e as divergências foram resolvidas por um terceiro revisor. Incluímos estudos de fase IV, com no mínimo três meses de duração. No total foram estudados 760 pacientes; o fator antinuclear, o anticorpo anti-DNA de dupla hélice e os antígenos extraídos pela salina foram os mais verificados. De todos os pacientes, apenas 10 (1,3%) apresentaram manifestações clínico-laboratoriais de lúpus induzido por infliximabe.

The present systematic review aims to discuss infliximab-induced autoantibodies and subsequent onset of systemic lupus erythematosus (SLE) through the analyses of primary reports measuring autoantibodies both before and after the administration of infliximab for the treatment of several diseases - e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohn's disease. Our literature search was performed in nine databases - PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo and LILACS, and the search query retrieved 998 primary reports, from which 24 articles were selected and further narrowed down to 14, based on our inclusion criteria. Two independent reviewers performed the article selection and a third reviewer solved discrepancies. Our inclusion criteria comprised primary reports of phase IV clinical trials with duration of at least three months. In total, 760 patients were evaluated and the most prevalent assays performed in the studies were anti-nuclear antibodies (ANA), anti-double stranded DNA antibodies (anti-dsDNA), and antibodies to saline-extracted antigens (ENA panel). Of all patients evaluated, 10 (1.3%) showed clinical signs and laboratorial evidence of infliximabinduced SLE.

Benign fasciculations and corticosteroid use: possible association? An update.

Fasciculations are characterized by visible subtle and fast contractions of muscle, even wormlike in movement, by the contraction of a fascicle of muscle fibers. The authors present the case study of a 28-year-old patient with the appearance of migratory and diffuse fasciculations with an onset after partial tapering off of oral corticosteroides (60 mg total dose) indicated for treatment of Minimal change Glomerulopathy. Clinical Neurological physical exam allied with an ENMG, besides other complementary laboratory exams were used for screening the above-mentioned patient. Afterwards, current research relating to the topic at hand was made in order to update the data available in the Bireme, Scielo and PubMed Data Banks using the following key words: Fasciculation's, motor neuron disease, and benign fasciculations in the Portuguese, English as well as Spanish language. Although fasciculation's are most commonly associated with Motor neuron disease as well as with certain metabolic disorders, they may also be present in individuals with absolutely no underlying pathological disorders. In our case, fasciculation potentials that have been present for six months, with no other signs of a neurogenic disorder as well as absence of laboratory findings, the patient received a diagnosis of Benign Fasciculation Syndrome (BFS).We believe that the use of corticosteroides in high doses with subsequent tapering contributed to the fasciculation's, especially due to the changes that this causes on the ionic channels. Fasciculation's are symptoms seen in a large range of conditions, and also being the main symptom of the so-called Benign Fasciculation Syndrome. We have presented an example of this clinical syndrome in a patient whose complaint was fasciculation's, with complete clinical remission of symptoms following complete tapering off of corticosteroid six months previously.

NK cells in pregnant patients with SLE: a preliminary study / Estudo-piloto: células NK nas gestantes com LES

O sistema imune inato desempenha papel central na reprodução, tendo as células NK participação marcante. Durante a gravidez, seu comportamento pode esclarecer pontos cruciais na patogênese das complicações que podem ocorrer em gestantes com LES. OBJETIVO: Quantificar as células NK circulantes e sua viabilidade em gestantes com LES. MATERIAL E MÉTODOS: Avaliaram-se amostras de sangue de quatro grupos de dez pacientes cada: 1 GLES: Gestantes com LES; 2 PLES: Pacientes com LES não gestantes; 3 Gcontroles: Gestantes controles; 4 Controles: Mulheres não gestantes saudáveis. Em todas as pacientes, a quantidade e a viabilidade das células NK foram medidas por citometria de fluxo, assim como por apoptose total por coloração para anexina V e iodeto de propidium. RESULTADOS: Devido à variabilidade dos resultados, a mediana de cada grupo foi utilizada para avaliar: porcentagem CD56+ [GLES (0,10), PLES (0,12), Gcontroles (0,15), Controles (0,08)]; apoptose total [GLES (0,06), PLES (0,04), Gcontroles (0,11), Controles (0,11)]. Os resultados da contagem de células vivas tiveram baixa variabilidade, por isso média e desvio-padrão foram utilizados para comparação: [GLES (0,91 ± 0,06), PLES (0,95 ± 0,03), Gcontroles (0,86 ± 0,11), Controles (0,88 ± 0,08). CONCLUSÃO: Apesar de não terem alcançado valor de significância estatística, o percentual de apoptose total nos grupos com LES foi menor que o dos controles, e a porcentagem de células vivas foi maior. Isso sugere que, em pacientes com LES, grávidas ou não, as células NK têm vida útil prolongada (ou tem turnover menor/diferente), o que indica um maior estímulo imune, fazendo com que as células NK levem mais tempo para ativar o processo de apoptose.

The innate immune system plays an important role in reproduction, with marked involvement of NK cells. These cells behavior during pregnancy may clarify crucial points in the pathogenesis of complications that may occur in pregnant women with SLE. OBJECTIVE: To measure the amount of circulating NK cells and their viability in pregnant SLE patients. MATERIALS AND METHODS: Blood samples from four groups of ten patients each were evaluated: 1. GLES: Pregnant SLE patients; 2. PLES: Non-pregnant SLE patients; 3. Gcontrols: Pregnant controls; 4. Controls: Healthy non-pregnant women. In all patients the amount and viability of NK cells was measured by flow cytometry, as well as the total apoptosis by annexin V and propidium iodite staining. RESULTS: Due to the great variability, median of each group was used for evaluation: CD56+ count [GLES (0.10), PLES (0.12), Gcontrols (0.15), Controls (0.08)]; total apoptosis (addition of initial and late apoptosis to total number of dead cells) [GLES (0.06), PLES (0.04), Gcontrols (0.11), Controls (0.11)]. The results for live cells count had low variability, so the averages and standard deviations were used for comparisons: [GLES (0.91±0.06), PLES (0.95±0.03), Gcontrols (0.86±0.11), Controls (0.88+0.08)]. CONCLUSION: Although not statistically significant, the total apoptosis in the SLE groups was lower than in the control groups, and the live cell count was higher. This suggests that in SLE patients, pregnant or not, the NK cells have a prolonged life cycle (or have a lower/different turnover), and that there may be a higher immune stimulus making the NK cells take longer to activate the apoptosis process.

Imunidade na gestacão normal e na paciente com lúpus eritematoso sistêmico (LES) / Immunity in the normal pregnancy and in the patient with systemic lupus erythematosus (SLE)

A gravidez é uma condicão fisiológica na qual ocorrem várias mudancas imunoendócrinas com a finalidade de facilitar a imunossupressão e a tolerância aos antígenos paternos e fetais. Na gravidez humana normal existe uma relativa supressão de citocinas tipo Th1 na resposta dos linfócitos, levando a uma prevalência na resposta do tipo Th2. No LES, onde prevalece a resposta imune do tipo Th2, a gravidez pode estar relacionada com a ativacão da doenca. Este artigo é uma revisão dessas alteracões relacionadas com a resposta imune durante a gestacão normal e na da paciente com LES.