Iara T. Messias-Reason

Doença celíaca em crianças e adolescentes com síndrome de Down

OBJETIVOS: Alta prevalencia de doenca celiaca em pacientes com sindrome de Down tem sido descrita em varios paises. No entanto, no Brasil ainda nao ha relatos mostrando essa associacao. O presente estudo teve como objetivo avaliar a prevalencia de doenca celiaca em criancas e adolescentes com sindrome de Down no sul do Brasil. METODOS: Setenta e um pacientes (32 do sexo feminino e 39 masculino, 2-18 anos) provenientes de Curitiba, Brasil, foram estudados. Oitenta individuos (42 do sexo masculino e 38 feminino, 2-19 anos) foram utilizados como controles do estudo. Todas as amostras foram investigadas para anticorpo anti-endomisio (EmA) e anti-transglutaminase tecidual (anti-tTG). O EmA foi pesquisado atraves de imunofluorescencia indireta usando cordao umbilical como substrato e o anti-tTG atraves da tecnica de ELISA, utilizando transglutaminase tecidual como antigeno. As dosagens de IgA foram realizadas por turbidimetria. RESULTADOS: Cinco pacientes com sindrome de Down (7%) foram positivos para EmA-IgA, com titulos entre 1/5 e 1/80 e catorze (17,5%) para anti-tTG (21-340 unidades). Todos os pacientes positivos para EmA apresentaram simultaneamente positividade para o anti-tTG. Os achados clinicos e histologicos na mucosa intestinal confirmaram doenca celiaca em quatro pacientes. O outro paciente EmA positivo nao foi submetido a biopsia duodenal. Os pacientes positivos apenas para anti-tTG apresentaram valores limitrofes (< 25 unidades) e eram assintomaticos. Nenhum individuo do grupo controle foi positivo para EmA ou anti-tTG. Nenhuma amostra do estudo foi deficiente para IgA. CONCLUSOES: Os dados do presente estudo mostram alta prevalencia (5,6%) de doenca celiaca confirmada em criancas e adolescentes com sindrome de Down da regiao sul do Brasil.

High positivity of anti-CCP antibodies in patients with Down syndrome

The aim of the present study was to evaluate the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in patients with Down’s syndrome (DS) previously tested for IgM rheumatoid factor (RF) and to correlate the results with clinical findings. Eighty-eight patients with DS previously tested for IgM-RF were divided into two groups matched for sex and age. Group A consists of 42 RF positive patients and group B of 44 RF negative patients. The presence of anti-CCP antibody was determined using a second-generation enzyme-linked immunosorbent assay. A total of 52.3% (45/86) of DS patients were positive for anti-CCP antibodies. Twenty-four patients (57.1%) of the RF positive group and 21 (47.7%) of the RF negative group presented anti-CCP circulating antibodies. The concordance between both tests was 54.6%. None of the patients had clinical evidence of rheumatoid arthritis or juvenile idiopathic arthritis. Although a high prevalence of anti-CCP antibodies was observed in DS patients, no association has been found presently with clinical disease. Careful follow-up of these patients will be necessary to clarify the real significance of these findings.

Triagem sorológica de familiares de pacientes com doença celíaca: anticorpos anti-endomísio, antitransglutaminase ou ambos?

BACKGROUND Celiac disease is the most common intestinal disorder of caucasian populations and presents a prevalence of 8% to 18% between the relatives of patients. The anti-endomysial (IgA-EmA) and anti-tissue transglutaminase antibodies (IgA-tTG) have represented an important non invasive and sensitivity method of screening and diagnosis of celiac disease in risk groups and populations. AIM To investigate the prevalence of IgA-EmA and IgA-tTG antibodies in relatives of celiac patients and verify the degree of concordance between them. METHODS One hundred and seventy seven relatives of celiac patients (76(feminino); 101(masculino); 2-79 years) and 93 healthy individuals were evaluated (34(feminino); 59(masculino); 2-71 years). IgA-EmA were detected by indirect immunofluorescence, with human umbilical cord as substrate, while anti-IgA-tTG titers were measured by enzyme-linked immunosorbent assay (ELISA), using commercial kit. RESULTS Total positivity to antibodies in relatives of celiac patients was of 21% (37/177), and showed significant difference compared to control group (0%; 0/93). Twelve percent (21/177) of celiac disease relatives were positive to IgA-EmA, 13.56% (24/177) to IgA-tTG, and 4.52% (8/177) to both assays simultaneously. The concordance between both methods was 83.6% (148/177) and the discordance was 16.4% (29/177), with a positive and significant correlation (r = 0.435). Among the concordant results, 79.1% (140/177) were negative and 4.52% (8/177) were positive to both antibodies. Among the discordant results, 7.34% (13/177) were positive to IgA-EmA and negative to IgA-tTG, while 9.04% (16/177) were negative to IgA- EmA and positive to IgA-tTG. CONCLUSION Although the high positivity to IgA-EmA and IgA-tTG emphasizes the importance of the serological screening in relatives of celiac patients, the discordances detected in this study showed that the use of only one method can lead to false negative results. Consequently these relatives will not be submitted to intestinal biopsy to confirm the diagnosis of celiac disease, and to the correct and earlier treatment.

Autoantibodies in relatives of celiac disease patients: a follow-up of 6-10 years

CONTEXT Autoimmune diseases are 3 to 10 times more frequently in patients with celiac disease and their relatives than in the general population. OBJECTIVE To investigate a broad spectrum of autoantibodies in celiac disease relatives from Southern Brazil, in a serological follow-up of 6-10 years, aiming to associate with other autoimmune diseases, degree of parentage, demographic and clinical data. METHODS Serum samples of 233 relatives were analyzed in two different phases: n = 186 in phase I (1997-2000) and n = 138 (being 91 = follow-up group and 47 = newly tested) in phase II (2006-2007). As controls, 100 unrelated individuals were evaluated. Autoantibodies to smooth muscle, mitochondrial, liver-kidney microssome, parietal cell and thyroid microssome were tested by indirect immunofluorescence. RESULTS A significant increase of autoantibodies, in both phases, was observed in the relatives when compared to the non-relatives (P = 0.0064), specifically to anti-thyroid microssome and anti-parietal cell. In both phases, the female/male proportion of autoantibodies was of 4:1 to 3:1 (P<0.041). The frequency of autoantibodies amongst 1st and 2nd degree relatives was 11.8% and 9.68% in phase I and 4% and 6.67% in phase II. CONCLUSION Celiac disease relatives presented other autoantibodies and serological screening is a useful instrument for identifying autoimmune diseases along the years.

BF*F allotype of the alternative pathway of complement: A marker of protection against the development of antiphospholipid antibodies in patients with systemic lupus erythematosus

Background B factor (BF) from the alternative complement pathway seems to participate in the pathophysiology of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Objective To study the allotypic variability of BF in SLE and their associations with clinical and autoantibodies profile. Methods BF allotypes were determined by high-voltage agarose gel electrophoresis, under constant cooling, followed by immunofixation with anti-human BF antibody, in 188 SLE patients and 103 controls. Clinical and serological data were obtained from medical examination and records. Results No significant differences of BF variants between patients and controls were found, neither in relation to epidemiologic or clinical manifestations. Associations of phenotype BF SS07 and allotype BF*S07 were found with anticardiolipin IgM (aCl-IgM) antibodies (p = 0.014 and p = 0.009 respectively), but not with aCl-IgG, lupus anticoagulant (LA), anti β2GPI or clinical APS. A significant decrease in BF*F allotype (p = 0.043) and BF SF phenotype (p = 0.018) was detected in patients with anti-phospholipid antibodies as a whole (aCl-IgG, aCl-IgM, LA and anti β2GPI). Conclusions There is a link between phenotype BF SS07 and allotype BF*S07 with aCl-IgM in SLE patients; BF*F allotype could be considered a marker of protection against the development of antiphospholipid antibodies in these patients.

Analysis of four serum biomarkers in rheumatoid arthritis: association with extra articular manifestations in patients and arthralgia in relatives

OBJECTIVES To evaluate the frequency of four serum biomarkers in RA patients and their relatives and identify possible associations with clinical findings of the disease. METHODS This was a transversal analytical study. Anti-cyclic citrullinated peptide (anti-CCP), anti-mutated citrullinated vimentin (anti-MCV) and IgA-rheumatoid factor (RF) were determined by ELISA and IgM-RF by latex agglutination in 210 RA patients, 198 relatives and 92 healthy controls from Southern Brazil. Clinical and demographic data were obtained through charts review and questionnaires. RESULTS A higher positivity for all antibodies was observed in RA patients when compared to relatives and controls (p<0.0001). IgA-RF was more frequent in relatives compared to controls (14.6% vs. 5.4%, p=0.03, OR=2.98; 95% CI=1.11-7.98) whereas anti-CCP was the most common biomarker among RA patients (75.6%). Concomitant positivity for the four biomarkers was more common in patients (46.2%, p<0.0001). Relatives and controls were mostly positive for just one biomarker (20.2%, p<0.0001 and 15.2%, p=0.016, respectively). No association was observed between the number of positive biomarkers and age of disease onset, functional class or tobacco exposure. In seronegative patients predominate absence of extra articular manifestations (EAMs) (p=0.01; OR=3.25; 95% CI=1.16-10.66). Arthralgia was present in positive relatives, regardless the type of biomarker. CONCLUSIONS A higher number of biomarkers was present in RA patients with EAMs. Positivity of biomarkers was related to arthralgia in relatives. These findings reinforce the link between distinct biomarkers and the pathophysiologic mechanisms of AR.