Evaluation of frequency of autoimmune hepatitis autoantibodies in children with type 1 diabetes / Frecuencia de anticuerpos de hepatitis autoinmune en niños con diabetes tipo I

Background: Diabetes mellitus type 1 (T1DM) is one of the childhood diseases with growing prevalence. Various accompanying autoimmune diseases were seen with type 1 diabetes. The most common autoimmune diseases with T1DM are autoimmune thyroiditis and celiac disease. In some reports, autoimmune hepatitis has been reported in association with DM-1. Objectives: The aim of this study was to evaluate autoimmune hepatitis autoantibodies in children with T1DM. Materials and methods: In this crosssectional study, 202 children with T1DM were evaluated (47.5% were males and 52.5% were girls). Liver enzymes, autoimmune hepatitis related autoantibodies such as anti-nuclear antibodies (ANA), anti-smooth muscle (ASMA) and anti liver and kidney microsomal antibodies (LKM-1) were measured. Liver ultrasound was done for participants and biopsy of liver was taken for children with increased echogenicity of the liver, hepatomegaly or elevated liver enzymes. Results analyzed by statistical software spss-16, Descriptive statistics and chi-square test, paired T-TEST. Level of less than 5% was considered statistically significant. Results: In 6 patients ANA and in 4 patients (2%) ASMA was positive,1 patient was ASMA positive but ANA negative. None of the patients were Anti LKM-1 positive. 3 patients had positive ANA and ASMA, and increased liver echogenicity on ultrasound simultaneously. Histological evaluation was showed that 2 patients had findings in favor of autoimmune hepatitis. Conclusion: Auto antibodies were positive in 10 cases. ANA was positive in 6 (2.97%) of all cases. ASMA was positive in 4 (1.98%) cases. Increased echogenicity was found in 3 cases. Histological evaluation showed 2 patients had biopsy confirmed autoimmune hepatitis. AIH-2 was not seen among our cases.

Antecedentes: La diabetes mellitus tipo 1 (DM1) es una de las enfermedades infantiles con mayor prevalencia. Se observaron varias enfermedades autoinmunes acompañantes con diabetes tipo 1. Las enfermedades autoinmunes más comunes con DM1 son la tiroiditis autoinmune y la enfermedad celíaca. En algunos reportes, se ha encontrado hepatitis autoinmune en asociación con DM-1. Objetivos: El objetivo de este estudio fue evaluar los autoanticuerpos de hepatitis autoinmunes en niños con DM1. Materiales y métodos: En este estudio transversal, se evaluaron 202 niños con DM1 (47,5% eran hombres y 52,5% eran niñas). Se midieron las enzimas hepáticas, los autoanticuerpos autoinmunes relacionados con la hepatitis, como los anticuerpos antinucleares (ANA), el músculo liso (ASMA) y los anticuerpos microsomales hepáticos y renales (LKM-1). Se realizó una ecografía hepática para los participantes y se tomó una biopsia del hígado para niños con mayor ecogenicidad del hígado, hepatomegalia o enzimas hepáticas elevadas. Los resultados fueron analizados por el software estadístico spss-16 usando estadística descriptiva y prueba de chi-cuadrado, T-TEST pareado. Se consideró estadísticamente significativo un nivel menor del 5%. Resultados: En 6 pacientes con ANA y en 4 pacientes (2%) ASMA fue positiva, 1 paciente fue ASMA positiva pero ANA negativa. Ninguno de los pacientes fue anti LKM-1 positivo. 3 pacientes tuvieron ANA y ASMA positivas, y aumentaron la ecogenicidad hepática en la ecografía simultáneamente. La evaluación histológica mostró que 2 pacientes tenían hallazgos a favor de la hepatitis autoinmune. Conclusión: Los autoanticuerpos fueron positivos en 10 casos. ANA fue positivo en 6 (2,97%) de todos los casos. La ASMA fue positiva en 4 (1,98%) casos. Se encontró mayor ecogenicidad en 3 casos. La evaluación histológica mostró que 2 pacientes tenían biopsia confirmada de hepatitis autoinmune. AIH-2 no fue visto entre nuestros casos.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes / Hepatite autoimune em 828 crianças e adolescentes brasileiros: achados clínicos e laboratoriais, perfil histológico, tratamentos e resultados

Abstract Objective: This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. Methods: The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. Results: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). Conclusions: In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.

Resumo Objetivo: Este estudo com acompanhamento de longo prazo visou a avaliar o quadro clínico, os achados laboratoriais, o perfil histológico, os tratamentos e os resultados de crianças e adolescentes com hepatite autoimune. Métodos: Foram analisados os prontuários médicos de 828 crianças e adolescentes com HAI. Foi usado um questionário para coletar os dados anônimos sobre o quadro clínico, os achados bioquímicos e histológicos e os tratamentos. Resultados: De todos os pacientes, 89,6% tinham hepatite autoimune-1 e 10,4% hepatite autoimune-2. O sexo feminino foi predominante nos dois grupos. A idade média no início dos sintomas foi 111,5 (6; 210) e 53,5 (8; 165) meses nos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. Foi observado início clínico agudo em 56,1% e 58,8% e sintomas insidiosos em 43,9% e 41,2% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. A probabilidade de insuficiência hepática foi 1,6 vezes maior para hepatite autoimune-2; 3,6% e 10,6% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente, apresentaram insuficiência hepática fulminante; o risco foi 3,1 vezes maior para hepatite autoimune-2. Os níveis de gamaglobulina e imunoglobulina G foram significativamente maiores nos pacientes com hepatite autoimune-1, ao passo que os níveis de imunoglobulina A e C3 foram menores em pacientes com hepatite autoimune-2; 22,4% dos pacientes apresentaram cirrose e a remissão bioquímica foi atingida em 76,2%. A taxa de sobrevida atuarial foi de 93,0%. Um total de 4,6% pacientes foram submetidos a transplante de fígado e 6,9% morreram (hepatite autoimune-1: 7,5%; hepatite autoimune-2: 2,4%). Conclusões: Nesta grande série clínica de crianças e adolescentes brasileiros, a hepatite autoimune-1 foi mais frequente e os pacientes com hepatite autoimune-2 mostraram maiores taxas de remissão da doença com respostas mais rápidas aos tratamentos. Os pacientes com hepatite autoimune-1 apresentaram maior risco de óbito.

A evolução do diagnóstico da doença mista do tecido conjuntivo / Evolution of the diagnosis of mixed connective tissue disease

A Doença Mista do Tecido Conjuntivo (DMTC) é uma doença autoimune crônica composta por um misto de quatro doenças: Lúpus Eritematoso Sistêmico, Esclerose Sistêmica, Dermatomiosite/Polimiosite e Artrite Reumatoide. Por se tratar de uma combinação de doenças autoimunes o diagnóstico é bastante complexo. Atualmente existem quatro combinações sugeridas por diferentes autores para a realização de um diagnóstico preciso, são eles: Kasukawa, Alarcón-Segovia e Villareal, Kahn e Appeboom e Sharp. Desde a sua descoberta em 1972 por Sharp, passaram-se 46 anos e desta forma o objetivo desta revisão foi verificar a evolução do diagnóstico da DMTC desde a sua descoberta até a atualidade. Para isso utilizou-se sites de busca PUBMED e SCIELO. Por se tratar de uma doença autoimune que leva ao desenvolvimento de um quadro inflamatório crônico utilizou-se a ferramenta STRING que permite a análise da interação de proteínas. Até a presente data, não existe um consenso de qual critério deve ser usado para o diagnóstico correto e eficiente desta doença. A baixa relação de interações observadas a partir da ferramenta STRING demonstra que ainda não existem dados suficientes na literatura para que a ligação entre proteínas marcadoras e a DTMC possa ser estabelecida. (AU)

Mixed connective tissue disease (MCTD) is a chronic autoimmune disorder consisting of a mixture of four diseases: systemic lupus erythematosus, systemic sclerosis, dermatomyositis/polymyositis, and rheumatoid arthritis. Because it is a combination of different autoimmune disorders its diagnosis is quite complex. Currently there are four combinations suggested by the following authors to establish an accurate diagnosis: Kasukawa, Alarcón-Segovia & Villareal, Kahn, and Appeboom & Sharp. It has been 46 years since Sharp reported the disease in 1972 and thus the purpose of this review was to investigate the evolution of the diagnosis of MCTD since then. PubMed and SciELO databases were used for this investigation. Because MCTD is an autoimmune disease that leads to the development of a chronic inflammatory condition, the STRING tool was used to allow the analysis of protein interaction. To date, there is no consensus as to what criterion should be used for a correct and efficient diagnosis of this disease. The low ratio of interactions observed from the STRING tool demonstrates that there is not yet enough data in the literature for establishing the binding between marker proteins and MCTD. (AU)

The evaluation of the Myxovirus Resistance 1 protein in serum and saliva to monitor disease activation in primary Sjögren's syndrome

OBJECTIVE: Primary Sjögren's syndrome (pSjS) is a chronic autoimmune disease that causes dry eye and mouth. No laboratory parameters to monitor the activation of this disease have been identified. Therefore, any possible relationships between salivary and blood myxovirus resistance 1 (MX1) and pSjS must be prospectively studied. METHODS: Thirty female patients with pSjS, 30 women with rheumatoid arthritis (RA) without secondary Sjögren's syndrome (SjS) and 28 healthy control women were enrolled in this investigation. Analyses of MX1 by the enzyme-linked immunosorbent assay (ELISA) method, SS-A (Ro) and SS-B (La) tests by the strip immunoblot method, anti-nuclear antibody (ANA) tests by immunofluorescence and the measurement of serum rheumatoid factor (RF), C3, C4, immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) were performed. RESULTS: The serum level of MX1 in patients without Raynaud phenomenon was higher than in those with Raynaud phenomenon (p:0.029, p<0.05, statistically significant). There was a statistically significant positive association between hemoglobin levels and MX1 serum levels. No statistically significant association was found among the other parameters. Low MX1 levels were shown to be associated with both a low disease activity score based on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and hydroxychloroquine use in all patients. CONCLUSION: MX1 levels have a considerable impact on the assessment of the disease activity in SjS. We believe that more-comprehensive studies should be performed on patients with pSjS who do not use hydroxychloroquine to prove this relationship and that MX1 levels should be used as a routine marker for the assessment of pSjS disease activity. Further studies are needed to create awareness of the role that MX1 has in the diagnosis of pSjS, which may help to uncover novel pathways for new therapeutic modalities.

Cut-off values of immunological tests to identify patients at high risk of severe lupus nephritis

Cut-off values for anti-dsDNA, anti-nucleosome and anti-C1q antibodies tests and for complement-mediated hemolytic activity (CH50) were explored to identify patients with high risk of developing severe lupus nephritis (LN). Forty-one patients with confirmed systemic lupus erythematosus (SLE) were identified; their levels for the three antibodies and complement had been measured on a same serum sample. These patients were classified based on the presence of renal involvem ent; sixteen had active proliferative LN. With the cut-off values accepted in the laboratory for SLE diagnosis (anti-dsDNA > 100 UI/ml, anti-nucleosome > 50 U/ ml or CH50 < 190 UCH50%) no significant differences were found between patients with and without LN. Anti-C1q > 40 U/ml showed a statistically significant association with LN and had 80% of specificity. Cut-off values for LN identified by Receiver Operating Characteristic curves (ROC) were higher for anti-dsDNA (> 455 IU/ml) and anti-nucleosome (>107 U/ml), lower for CH50 (< 150 UCH50%) and, for anti-C1q (> 41 U/ml) coincided with the cut-off values accepted for SLE. Anti-C1q > 134 U/ml had a 92% of specificity, 56% of sensibility and was associated with a fifteen-fold increased risk of LN. The simultaneous presence of anti-nucleosome > 107 U/ml and anti-C1q > 134 U/ml was associated with a 27-fold higher probability for LN. According to these results, the cut-off values used to detect SLE activity could be inadequate to identify patients at high risk of severe LN.

Se exploraron valores de corte para los ensayos de anti-ADNdc, anti-nucleosoma, anti-C1q y complemento hemolítico total (CH50) capaces de identificar los casos con mayor riesgo de nefritis lúpica (NL) grave. Se seleccionaron 41 pacientes ≥ 16 años con lupus eritematoso sistémico (LES) confirmado que tenían titulados los niveles de los tres anticuerpos y CH50, en una misma muestra de suero. Fueron clasificados según presencia de compromiso renal; 16 presentaron formas proliferativas de NL activa. Con los valores de corte aceptados por el laboratorio para el diagnóstico de LES (anti-ADNdc > 100 UI/ml, anti-nucleosoma > 50 U/ml o un CH50 < 190 UCH50%) no se encontraron diferencias significativas entre casos con y sin NL. Un anti-C1q > 40 U/ml tuvo una especificidad del 80% y mostró una asociación estadísticamente significativa con NL. Al aplicar curvas Receiver Operating Characteristic (ROC) para NL, se identificaron valores de corte más altos para anti-ADNdc (> 455 IU/ml) y anti-nucleosoma (> 107 U/ml), más bajo para CH50 (< 150 UCH50%) y para el anti-C1q (> 41 U/ml) coincidió con el aceptado para diagnóstico de LES. Un anti-C1q > 134 U/ml presentó una sensibilidad del 56%, una especificidad del 92% y se asoció con quince veces más riesgo de NL. La presencia simultánea de anti-C1q > 134 U/ml y anti-nucleosoma > 107 U/ml se asoció 27 veces más riesgo de NL. De acuerdo a estos resultados los valores de corte empleados para actividad en pacientes con LES podrían resultar inadecuados para identificar pacientes con mayor riesgo de NL grave.

T cell subsets and immunoglobulin G levels are associated with the infection status of systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder that affects nearly all organs and tissues. As knowledge about the mechanism of SLE has increased, some immunosuppressive agents have become routinely used in clinical care, and infections have become one of the direct causes of mortality in SLE patients. To identify the risk factors indicative of infection in SLE patients, a case control study of our hospital's medical records between 2011 and 2013 was performed. We reviewed the records of 117 SLE patients with infection and 61 SLE patients without infection. Changes in the levels of T cell subsets, immunoglobulin G (IgG), complement C3, complement C4, globulin, and anti-double-stranded DNA (anti-ds-DNA) were detected. CD4+ and CD4+/CD8+ T cell levels were significantly lower and CD8+ T cell levels were significantly greater in SLE patients with infection than in SLE patients without infection. Additionally, the concentrations of IgG in SLE patients with infection were significantly lower than those in SLE patients without infection. However, complement C3, complement C4, globulin, and anti-ds-DNA levels were not significantly different in SLE patients with and without infection. Therefore, clinical testing for T cell subsets and IgG is potentially useful for identifying the presence of infection in SLE patients and for distinguishing a lupus flare from an acute infection.

Depression, sexuality and fibromyalgia syndrome: clinical findings and correlation to hematological parameters / Depressão e sexualidade na síndrome fibromiálgica: achados clínicos e correlação com parâmetros hematológicos

ABSTRACT Fibromyalgia (FM) is characterized by chronic pain and comorbidities. Objective To investigate sexuality and depression in women with FM compared with controls and to correlate the findings with hematological parameters. Methods 33 women with FM and 19 healthy women were included and evaluated with the following instruments: Female Sexual Function Index, Beck Inventory, Visual Analogue Scale, medical history and laboratory exams. Results The prevalence of sexual dysfunction (P = 0.007) and depression (P < 0.001) were higher in the study group than in the control group; they were positively correlated (P = 0.023). The study group showed lower serum concentrations of testosterone, free T4, antinuclear factor, and lower blood hemoglobin and hematocrit. Conclusions FM was associated with high scores of sexual dysfunction and depression, and there were correlations with hematological parameters. We suggest the involvement of immune-inflammatory mediators and FM, which need further investigation to understand their role in FM syndrome and its comorbidities.

RESUMO Fibromialgia (FS) é caracterizada por dor e comorbidades. Objetivo investigar depressão e sexualidade em mulheres com FS comparadas a controles, e correlacionar os achados com parâmetros hematológicos. Métodos 33 mulheres com FS e 19 controles saudáveis foram incluídas e avaliadas através dos seguintes instrumentos: Índice de Função Feminina Sexual, Inventário de Beck, escala visual analógica, história médica e exames laboratoriais. Resultados A prevalência de disfunção sexual (P = 0,007) e depressão (P < 0,001) foram maiores no grupo de estudo do que nos controles; também houve correlação positiva (P = 0,023). O grupo de estudo apresentou menor concentração sérica de testosterona, T4 livre, fator antinuclear e menos concentração de hemoglobina e hematócrito. Conclusões A FS associou-se com altos índices de disfunção sexual e depressão, e houve correlação com os parâmetros hematológicos estudados. Sugere-se o envolvimento de mediadores imuno-inflamatórios na FS, que necessita de maior investigação para a compreensão dos mecanismos tanto na FS e quanto em suas comorbidades.

Teleducation about Cleft Lip and Palate: An Interdisciplinary Approach in the Promotion of Health

Introduction The Young Doctor Project (YDP) uses Telehealth and Interactive Teleducation instruments to promote the integration of different areas of health and to build knowledge. This methodology can also foster public awareness on various issues related to health. In this context, the objective of this study was to emphasize cleft lip and palate (CLP), which is one of the most common birth defects in Brazil. Objective The study aimed to apply a model of education regarding CLP, based on the dynamics of the YDP, and to evaluate the participants' knowledge acquired after participating in the YDP. Methods The participants were 41 students, 13 to 15 years of age and at the eight- and ninth-grade levels in a private elementary school in Bauru (Brazil). To analyze the performance of the participants, a questionnaire was administered before and after the completion of the training program. The training program was structured in three steps using: (1) interactive teleducation classes, (2) a cybertutor, and (3) practical activities. Results There was a statistically significant difference between the pre- and postparticipation questionnaire results. The improved performance of participants is evidenced by the increase in the rate of correct answers on all issues. Conclusion The YDP on CLP was applied in the school setting following the three steps recommended by the project, and, after the implementation of the training program, there was a significant increase in participants' knowledge of CLP. The YDP on CLP proved an effective tool in promoting health education. .

A Case of Autoimmune Hepatitis Combined with Graves' Disease / 대한소화기학회지

A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg during a period of 2 weeks. Laboratory tests showed elevated levels of liver enzymes (AST 1,282 IU/L, ALT 1,119 IU/L) and total bilirubin (6.4 mg/dL); negative for hepatitis virus infection; elevated serum levels of triiodothyronine (T3, 3.60 ng/dL), free thyroxine (fT4, 3.82 ng/dL), and lowered serum level of thyroid stimulating hormone (TSH, <0.025 microIU/mL); and positive for thyroid stimulating antibody and anti-mitochondrial antibody (AMA). The liver biopsy findings were consistent with autoimmune hepatitis (AIH). Accordingly, oral steroid therapy was started with 60 mg of prednisolone under the impression of AIH associated with Graves' disease. After a week of steroid therapy, the clinical manifestation showed significant improvement, with normalization of both liver and thyroid functions. Diagnosis of the liver condition of patients who present with hyperthyroidism and liver dysfunction is important, so that appropriate therapy can be promptly initiated.

A Study on Pulmonary Complications of Systemic Sclerosis in Eastern India.

Aim. This study was undertaken to find out the characteristics of clinical, radiological and functional changes affecting the respiratory system in patients with systemic sclerosis (SSc) from eastern India, and the association of these characteristics with pulmonary hypertension. Methods. This was a cross-sectional, observational study involving 46 patients. Other than the routine tests, anti-nuclear antibody (ANA), spirometry, diffusing capacity of lung for carbon monoxide (DLCO) measurement, chest radiograph, highresolution computed tomography (HRCT) of thorax, 6-minute walk test and echocardiography were done. Results. Out of a total of 46 patients, 27 patients had diffuse cutaneous SSc (dcSSc) and 19 had limited cuteaneous SSc (lcSSc). Eleven patients had pulmonary hypertension. The HRCT revealed diffuse parenchymal lung disease (DPLD) in 32 (65%) cases. The ANA was positive in 83% cases. Anti-Scl70 was found in 41% of patients with dcSSc and anti-centromere antibody was found in 47% of patients with lcSSc. Spirometry revealed restrictive pattern in 30 patients; 9 had obstruction; and the rest were normal. The DLCO was abnormal in 38 patients. A strong correlation was found between reduction in DLCO and pulmonary artery systolic pressure (PASP). Also, a strong association was observed between a drop of >4% in oxygen saturation on 6-minute walk test and presence of pulmonary arterial hypertension (PAH). Conclusions. Majority of the patients with SSc had restrictive lung disease with abnormal DLCO and features resembling non-specific interstitial pneumonia. Nucleolar ANA was predominantly found in patients having PAH. Presence of DPLD had a negative association with presence of anti-centromere antibody. Reduction in DLCO and a fall of >4% in oxygen saturation on 6-minute walk test may be used as predictors of PAH in asymptomatic individuals.

Deteccao de anticorpos antinucleares por imunofluorescencia indireta em celulas HEp-2: definindo a diluicao de triagem adequada para o diagnostico das doencas reumaticas autoimunes / Detection of anti-nuclear antibodies by indirect immunofluorescence on HEp-2 cells: setting the appropriate screening dilution for the diagnosis of autoimmune rheumatic diseases

Objetivo: Definir o título anormal e a diluição de triagem adequada para o teste de FAN (fator antinúcleo) por imunofluorescência indireta em células HEp-2 (FAN HEp-2). Métodos: Realizamos a pesquisa do FAN HEp-2 em amostras de soro de 126 indivíduos saudáveis. As amostras foram triadas na diluição de 1:80, e aquelas positivas diluídas até o título de 1:5120. O título anormal de FAN foi definido como aquele correspondente ao percentil 95 do teste nesta população. A sensibilidade dos diferentes títulos do FAN foi determinada em um grupo de 136 pacientes com diagnóstico de doença reumática autoimune, e a especificidade em um grupo de 118 pacientes com diagnóstico de outras doenças reumáticas. O valor de corte ótimo do teste foi determinado pelo estudo da curva ROC. Resultados: A frequência de FAN positivo em indivíduos saudáveis foi de 13,2%. Não houve diferença na frequência de resultados positivos de acordo com o gênero ou a idade. O título anormal do FAN foi definido como a diluição de 1:160. A diluição dos soros de 1:80 apresentou sensibilidade de 87,7% e especificidade de 67,8%, enquanto a diluição de 1:160 apresentou sensibilidade de 82% e especificidade de 73,7%. Pela análise da curva ROC, a diluição de 1:160 correspondeu ao valor de corte ótimo. Conclusão: O título anormal e o valor de corte ótimo do FAN HEp-2 na população avaliada foram de 1:160. A diluição de 1:160 é, portanto, a diluição de triagem ideal, com melhor especificidade, porém sem comprometimento significativo da sensibilidade diagnóstica do teste. .

Objective: To establish the abnormal title and the appropriate screening dilution for ANA (antinuclear antibodies) test by indirect immunofluorescence on HEp-2 cells (ANA HEp-2). Methods: An analysis of ANA Hep-2 in serum samples from 126 healthy individuals was performed. The samples were screened at a dilution of 1:80, and those positive were diluted to the title of 1:5120. The abnormal title of ANA was defined as that corresponding to the 95th percentile of the test in this population. The sensitivity of the different titles of antinuclear antibodies was determined in a group of 136 patients with a diagnosis of autoimmune rheumatic disease, and the specificity was determined in a group of 118 patients with other rheumatic diseases. The optimal cutoff value of the test was determined by ROC curve analysis. Results: The frequency of ANA positivity in healthy subjects was 13.2%. There was no difference in the frequency of positive results according to gender or age. The abnormal title of ANA was defined as the dilution of 1:160. The 1:80 dilution had sensitivity of 87.7% and specificity of 67.8%, while the 1:160 dilution had sensitivity of 82% and specificity of 73.7%. By ROC curve analysis, a dilution of 1:160 corresponded to the optimal cutoff value. Conclusion: The abnormal title and the optimal cutoff value of ANA HEp-2 in the population was 1:160. Therefore, the dilution of 1:160 is the optimal screening dilution, with better specificity but without significantly compromising the sensitivity of the diagnostic test. .

Utilidade da triagem dos anticorpos anti-dsDNA por quimioluminescência, seguida de confirmação por imunofluorescência indireta / Usefulness of anti-dsDNA antibody screening with chemiluminescence followed by confirmation by indirect immunofluorescence

OBJETIVO: Avaliar o desempenho de um imunoensaio quimioluminescente (CLIA) para os anticorpos anti-dsDNA, utilizando como referência o teste de imunofluorescência indireta (IFI) sobre Crithidia luciliae. MÉTODOS: O sistema de automação foi previamente aprovado com 81% de eficiência, 100% de sensibilidade e 82% de especificidade, por processo de validação intrínseca em 179 amostras consecutivas de 169 pacientes no início de 2011. A seguir, esses pacientes foram subdivididos em três grupos de acordo com os resultados da pesquisa dos anticorpos anti-dsDNA nas duas metodologias (reagentes, não reagentes e resultados discrepantes). RESULTADOS: Na análise dos dados: 1) 77% (129/169) dos exames haviam sido solicitados por médicos reumatologistas; 2) 57% (97/169) das amostras eram de pacientes lúpicos; 3) Os resultados de CLIA, reagentes e não reagentes, estavam bem definidos e padronizados; 4) A automação reduziu em 70% as passagens pela técnica manual com segurança e qualidade; 5) A alta prevalência de pacientes lúpicos e com nefrite entre os resultados de CLIA falso-positivos corrobora a hipótese de que o índice real de falsa positividade do CLIA seja menor que o encontrado inicialmente neste estudo.

OBJECTIVE: The purpose of this study was to evaluate the performance of a chemiluminescent immunoassay (CLIA) to detect anti-dsDNA antibodies, using the indirect immunofluorescence test (IIF) on Crithidia luciliae as a reference. METHODS: The automation system demonstrated 81% efficiency, 100% sensitivity and 82% specificity according to the intrinsic validation process performed using 179 consecutive samples from 169 patients in the beginning of 2011. These patients were subsequently divided into 3 groups according to the co-reactivity of anti-dsDNA results using the 2 methods (reactive, non-reactive and discrepant results). RESULTS: Upon data analysis, 77% (129/169) of the tests were requested by rheumatologists, and 57% (97/169) of the samples were from lupus patients. Both the reactive and non-reactive results of the CLIA were well defined and standardised, and automation reduced the manual labor required by 70% in a safe and high-quality manner. Furthermore, the high prevalence of patients with lupus and nephritis among the CLIA false-positive results corroborates the hypothesis that the actual index of CLIA false positivity is lower than that initially found in this study.

Higher serum levels of rheumatoid factor and anti-nuclear antibodies in helicobacter pylori-infected peptic ulcer patients

H. pylori infection has been associated with some autoimmune disorders. The aim of this study was to evaluate the serum concentrations of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected peptic ulcer patients, H. pylori-infected asymptomatic carriers and a healthy control group. A Total of 100 H. pylori-infected peptic ulcer patients, 65 asymptomatic carriers and 30 healthy H. pylori-negative subjects [as a control group] were enrolled into study. Serum samples of participants tested for the levels of rheumatoid factor and anti-nuclear antibodies by use of ELISA. The mean serum levels of rheumatoid factor and anti-nuclear antibodies in peptic ulcer group was significantly higher in comparison to the control group [p<0.05]. Although, the mean serum levels of rheumatoid factor and anti-nuclear antibodies in the asymptomatic carriers group was higher than those in the control group, the difference was not statistically significant. No significant differences were observed between peptic ulcer patients and asymptomatic carriers groups regarding the mean serum levels of rheumatoid factor and anti-nuclear antibodies. The mean serum levels of rheumatoid factor in men with peptic ulcer was significantly higher compared to the group of healthy men [p<0.05]. Although in female of peptic ulcer patients or asymptomatic carriers groups, the mean serum levels of rheumatoid factor was higher than that in healthy women, but the differences were not statistically significant. Also, no significant differences were observed between men and women with peptic ulcer, asymptomatic carriers control groups based on the serum levels of anti-nuclear antibodies. The results showed higher serum levels of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected patients with peptic ulcer disease which represent the H. pylori-related immune disturbance in these patients. Additional follow-up studies are necessary to clarify the clinical significance of these autoantibodies in patients with H. pylori infection

Cirrosis biliar primaria: aspectos clinico- epidemiológicos en una población uruguaya / [Primary biliary cirrhosis: clinical and epidemiological features in an Uruguayan population].

INTRODUCTION: Primary biliary cirrhosis (PBC) is a chronic cholestatic, autoimmune, liver disease produced by inflammation and destruction of the interlobular bile ducts. It is more frequent among female patients and is usually diagnosed in the fifth decade of life. OBJECTIVE: Our objective was to describe the clinical and epidemiological characteristics of patients with PBC in Uruguay. MATERIAL AND METHODS: This descriptive study included patients from 3 medical centers diagnosed with PBC in the period January 2002 to September 2011. The diagnosis was based on the presence of at least two of the following requirements: cholestasis, antimitochondrial antibodies (AMA) (or AMA subtype 2) or positive antinuclear antibodies (ANA) (anticentromere pattern) and compatible biopsy. Data recorded were sex, age, symptoms, related illness, laboratory results, images and histology at the moment of the diagnosis. RESULTS: We included 81 patients, 94

were women and the mean age was 56 years old (range: 31 to 79 years old). Symptoms were present in 59 patients (73

) and pruritus, found in 51 of them (86

), was the most frequent symptom. Positive AMA was found in 84

of cases. Histological study was available in 35 patients (43

) and 13 of them (37

) had cirrhosis. The mean survival according to the presence or absence of cirrhosis was 9.17 years (95

confidence interval: 6.79-11.56) and 10.7 years (95

confidence interval: 9.27-12.14), respectively (P = 0.03). CONCLUSIONS: Female predominance and frequent association with other autoimmune diseases were confirmed in this group. Although there was a high percentage of symptomatic and cirrhotic patients at diagnosis, only the presence of cirrhosis was associated with a lower survival.

Electrolyte Imbalances and Nephrocalcinosis in Acute Phosphate Poisoning on Chronic Type 1 Renal Tubular Acidosis due to Sjogren's Syndrome

Although renal calcium crystal deposits (nephrocalcinosis) may occur in acute phosphate poisoning as well as type 1 renal tubular acidosis (RTA), hyperphosphatemic hypocalcemia is common in the former while normocalcemic hypokalemia is typical in the latter. Here, as a unique coexistence of these two seperated clinical entities, we report a 30-yr-old woman presenting with carpal spasm related to hypocalcemia (ionized calcium of 1.90 mM/L) due to acute phosphate poisoning after oral sodium phosphate bowel preparation, which resolved rapidly after calcium gluconate intravenously. Subsequently, type 1 RTA due to Sjogren's syndrome was unveiled by sustained hypokalemia (3.3 to 3.4 mEq/L), persistent alkaline urine pH (> 6.0) despite metabolic acidosis, and medullary nephrocalcinosis. Through this case report, the differential points of nephrocalcinosis and electrolyte imbalances between them are discussed, and focused more on diagnostic tests and managements of type 1 RTA.

Clinical Significance of Serum Autoantibodies in Idiopathic Interstitial Pneumonia

Although autoantibodies are routinely screened in patients with idiopathic interstitial pneumonia, there are no reliable data on their clinical usefulness. The aim of this study was to investigate the prognostic value of autoantibodies for predicting the development of new connective tissue disease in these patients and also mortality. We conducted retrospective analysis of the baseline, and follow-up data for 688 patients with idiopathic interstitial pneumonia (526 with idiopathic pulmonary fibrosis, 85 with nonspecific interstitial pneumonia, and 77 with cryptogenic organizing pneumonia) at one single tertiary referral center. The median follow-up period was 33.6 months. Antinuclear antibody was positive in 34.5% of all subjects, rheumatoid factor in 13.2%, and other specific autoantibodies were positive between 0.7%-6.8% of the cases. No significant difference in patient survival was found between the autoantibody-positive and -negative groups. However, the presence of autoantibodies, especially antinuclear antibody with a titer higher than 1:320, was a significant predictor for the future development of new connective tissue diseases (relative risk, 6.4), although the incidence was low (3.8% of all subjects during follow-up). In conclusion, autoantibodies are significant predictors for new connective tissue disease development, although they have no prognostic value.

Congenital and neonatal lupus erythematosus: two case reports / Lúpus eritematoso congênito e neonatal: relato de dois casos

Neonatal lupus erythematosus is an autoimmune disease produced by the passage of maternal antinuclear antibodies and extractable nuclear antigen antibodies through the placenta. At the moment of the diagnosis, the mothers are asymptomatic in 40 to 60% of cases. The most common manifestations are cutaneous lesions and congenital heart block. The cutaneous findings are variable and usually begin within the first weeks or months of life. Congenital lupus erythematosus is a congenital variant of neonatal lupus erythematosus. We present one case of congenital lupus erythematosus and one case of neonatal lupus erythematous, showing the variability of this disease.

Lúpus eritematoso neonatal é uma doença auto-imune produzida pela passagem de anticorpos maternos antinucleares e anticorpos contra antígenos extraíveis nucleares através da placenta. No momento do diagnóstico, as mães são assintomáticas em 40 a 60% dos casos. As manifestações mais comuns são lesões cutâneas e bloqueio cardíaco congênito. Os achados cutâneos são variáveis e geralmente começam nas primeiras semanas ou meses de vida. Lúpus eritematoso congênito é uma variante do lúpus eritematoso neonatal. Apresentaremos um caso de lúpus eritematoso congênito e um caso de lúpus eritematoso neonatal, mostrando a variabilidade da doença.

Jaccoud arthropathy in systemic lupus erythematosus: clinical and serological findings

OBJECTIVE: To study the prevalence of Jaccoud arthropathy (JA) in a sample of local systemic lupus erythematosus (SLE) patients and its clinical and serological associations. METHODS: 308 SLE patients from a single university center for the last two years were interviewed and examined. The presence of JA was searched for according to the JA index. After this, charts were reviewed for clinical and serological profile. RESULTS: The studied sample was composed by 94.5% females and 5.5% males with mean age of 38.08 ± 12.04 years and mean disease duration of 29.68 ± 11.63 years. A JA prevalence of 6.1% was found in this sample. There was a positive association of JA presence with arthritis complaints (p = 0.001) and a negative association with renal involvement (p = 0.028). Patients with JA had higher positivity for anti-dsDNA (p = 0.022). CONCLUSION: Despite the positive association of JA with arthritis and anti-dsDNA, there was a negative association with nephritis. This could suggest that JA patients belong with a SLE subset with a better prognosis.

Serum interleukin-17 & nitric oxide levels in patients with primary Sjögren's syndrome.

Background & objectives: The interleukin (IL)-17 producing T-helper cells have been linked to pathogenesis of autoimmunity and mostly investigated in rheumatoid arthritis (RA). In this study we tested the IL-17 levels, as well as the levels of nitric oxide (NO) as possible IL-17-induced product, in patients with primary Sjögren's syndrome (pSS), an intricate and complex chronic autoimmune disorder of exocrine glands. Methods: Serum IL-17 levels and nitrite concentrations determined in patients with pSS (n=30) were compared with the values obtained in patients with RA (n=10) and healthy controls (n=15). The values obtained for IL-17 in pSS patients were also associated with the patients’ clinical characteristics, particularly the rheumatoid factor (RF) and total antinuclear antibodies (tANA) levels. Results: Serum concentrations of IL-17 were significantly (P<0.01) higher in patients with pSS (12.9 ± 28.0 pg/ml) as compared to those obtained in healthy individuals (0.2 ± 0.6 pg/ml), but not as high as the values obtained for the patients with RA (34.5 ± 56.2 pg/ml). The mean IL-17 levels were significantly (P<0.05) higher in the pSS patients positive for rheumatoid factor (20.3 ± 33.3 pg/ml) than in RF-negatives (0.3 ± 0.6 pg/ml). Mean serum concentrations of IL-17 were also higher in antinuclear antibody (ANA)-positive samples (19.8 ± 33.5 pg/ml) in comparison to ANA-negative sera (1.1 ± 3.1 pg/ml) (P<0.05). The NO levels also showed elevated values in both pSS and RA patients, as compared to the healthy controls, since mean nitrite levels in patients with pSS and RA were 38.2 ± 29.2 μM and 41.7 ± 21.1 μM, respectively, while those in healthy controls were significantly lower, at 19.2 ± 10.5 μM. Interpretation & conclusions: The findings of this study showed that there was increased IL-17 and NO production in patients with primary SS, especially if they had associated elevated rheumatoid factor and antinuclear antibody values.