Anti-parietal cell antibodies in patients with autoimmune thyroid diseases.

BACKGROUND: Autoimmune thyroid disease (ATD) patients may have a higher prevalence of anti-parietal cell antibodies (APCA) than normal population. OBJECTIVE: To study the prevalence of APCA in a cohort of ATD patients to know its association with patient's clinical profile and gastrointestinal complaints. METHODS: APCA was sought for by indirect immunofluorescence test in 243 ATD patients: 136 (55.9%) with Graves' disease and 107 (44.0%) with Hashimoto's thyroiditis. A structured questionnaire for gastrointestinal symptoms, previous history of thrombosis, arthralgia and other autoimmune diseases in the patients and their families was applied. Positive and negative APCA individuals were compared. Positive patients were invited to perform upper gastrointestinal endoscopy and biopsy of duodenum segments. Sera from 100 healthy individuals from the same geographic area were used as controls. RESULTS: APCA was present in 20.1% (49/243) of ATD patients: 21.3% (29/136) in the Graves' sample and 18.6% (20/107) in the Hashimoto's sample (p = 0.61). Patients with positive APCA had more anemia (p = 0.03; OR = 2.89; 95% CI = 1.03-8.07) and less heartburn (p = 0.01; OR = 0.4; 95% CI = 0.20-0.83). Among the group of 49 APCA-positive patients, 24 agreed with upper endoscopy and it was found that 54.1% had atrophic gastritis. CONCLUSIONS: There is a high prevalence of positive APCA in ATD patients. APCA are more common in those with anemia and less common in those with complaints of heartburn. Almost half of positive APCA patients had atrophic gastritis.

Mannose-binding lectin serum levels in patients with systemic lupus erythematosus: association with thrombocytopaenia and seizure.

The complement system contributes to the pathogenesis of systemic lupus erythematosus (SLE). Mannose-binding lectin (MBL) is a key molecule of the lectin pathway of complement and seems to be related to the clinical manifestations of this disease. We evaluated the serum levels of MBL and its relationship with disease onset and clinical findings in SLE patients. Serum samples were analysed in 195 patients and 145 healthy controls from southern Brazil. Patients with high MBL levels (above 2000 ng/ml) showed a significant increase in the frequency of thrombocytopaenia ( p = 0.007; OR = 2.71; 95% CI = 1.32-5.55); and seizures ( p = 0.034; OR = 2.61; 95% CI = 1.07-6.37). A positive correlation between disease activity and MBL levels (>2000 ng/ml; p = 0.031, rho = 0.279) as well as of MBL concentration with accumulated organ damage ( p = 0.021; rho = 0.232) was observed. Our results suggest a role for MBL in the development of clinical manifestations such as thrombocytopaenia and seizures in SLE patients. These findings corroborate the participation of the lectin pathway of complement in the pathophysiologic mechanisms underlying clinical manifestations of SLE.

Lymphocytopenia is associated with anti-Beta-2 glycoprotein-1 in patients with 220 systemic lupus erythematosus.

BACKGROUND: Anti B2-Glicoprotein 1 (B2-GPI) is an antiphospholipid antibody that may be present in primary or secondary antiphospholipid syndrome (APS). Systemic Lupus erythematosus (SLE) is the main disease associated with secondary APS. OBJECTIVE: To study the prevalence of anti B2-GPI in SLE patients. METHODS: Anti B2-GPI (IgM/IgG) was studied by ELISA in 88 patients with SLE of both genders; 18.6% of which with secondary APS. Charts were reviewed for clinical and serological profile. RESULTS: Anti B2-GPI was present in 18.6% of the whole sample and in 29.4% of those with secondary APS. At univariated analysis, the presence of anti B2-GPI was more common in patients with serositis (p=0.04), lymphocytopenia (p=0.003) and anti cardiolipin (aCl) IgM antibodies (p=0.04). In a logistic regression study, only the associations with lymphocytopenia (OR=8.2; 95%CI=2.1-39.3) and aCl IgM (p=0.04; OR=3.4; 95%CI=1.05-11.1) remained significant. CONCLUSION: There is a 18.6% prevalence of positive anti B2-GPI in SLE population that is associated with the presence of aCl IgM and lymphocytopenia.

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 ß2GPI 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 ß2GPI). 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.

Association of complement factor B allotypes and serum biomarkers in rheumatoid arthritis patients and their relatives.

The aim of the study was to investigate the allotypic variability of complement factor B (BF) in patients and relatives with rheumatoid arthritis (RA) and its association with serological biomarkers and clinical features of the disease. BF allotypes were determined by high-voltage agarose gel electrophoresis in serum samples of 180 patients with RA, 198 relatives and 98 controls from Southern Brazil. Anticyclic citrullinated peptide (anti-CCP), antimutated citrullinated vimentin (anti-MCV) and IgA-rheumatoid factor (RF) were determined by ELISA and IgM-RF by latex agglutination in all samples. No significant differences were found in the allotypic variants of BF between patients with RA, relatives and controls, nor associations with gender and age of RA onset. BF*S07 allotype was significantly associated with extra-articular manifestations (EAMs; Secondary Sjögren Syndrome, pneumonitis, rheumatoid nodules) in patients with RA (P = 0.02; OR = 6.62). Patients with phenotype BF F had lower positivity for anti-MCV biomarker (P = 0.02; OR = 0.22) and those with allotype BF*S had higher prevalence of this autoantibody (P = 0.02; OR = 3.77). An increased frequency of RF-IgA was detected in relatives of patients with RA with BF FS07 phenotype (P = 0.02; OR = 7.78). Complement BF variability did not influence the development of RA in the studied patients, but BF variants may act as markers of disease prognosis, such as development of EAMs, corroborating with the role of the alternative pathway in the pathogenesis of RA.

Anti-CCP antibodies in Brazilian children and adults with juvenile idiopathic arthritis.

Patients with juvenile idiopathic arthritis (JIA) may need further care in the adult clinic as this disease frequently has continuous inflammatory activity during adult life. To identify which pediatric JIA patients will need continuing care into adulthood. We compared the clinical, serological, and demographic data of 45 JIA patients followed up by the pediatric clinic to those of 49 JIA patients in the adult rheumatology clinic. Patients in the adult clinic have older age at disease onset (p < 0.0001) and higher prevalence of positive anti-cyclic citrullinated peptide (CCP) (p = 0.05). No differences were observed in JIA form, presence of rheumatoid factor (RF), uveitis, and gender. Anti-CCP and older age at disease onset may identify pediatric JIA patients that will need further care in the adult clinic.

Low hepatitis B vaccine response in children with Down syndrome from Brazil.

BACKGROUND: It has been reported that vaccination against hepatitis B is less effective among people with Down syndrome than in the general population. We aimed to evaluate the rate of seroconversion to hepatitis B vaccine in children with Down syndrome from Brazil. METHODS: A total of 120 people with Down syndrome were included. All of them received the vaccine at intervals of 0, 30 and 180 days and serum samples were tested for the presence of antibodies to the hepatitis B surface antigen (anti-HBs) 30 days after the last dose. RESULTS: In the studied group, 58.3% (70/120) were male and 41.7% (50/120) female, with the median age of 5 years (range 2-15 years). Fifty-eight of 120 (48.3%) developed anti-HBs after vaccination. No association was found between gender and/or age and vaccine response. CONCLUSIONS: The low rate of seroconversion in response to hepatitis B vaccine suggests that all patients with Down syndrome immunized against hepatitis B should be followed and monitored by clinicians.

Spectrum of autoantibodies for gastrointestinal autoimmune diseases in systemic lupus erythematosus patients.

BACKGROUND: Organ-specific autoimmune diseases may appear in patients with systemic lupus erythematosus (SLE). Gastrointestinal symptoms are well documented in SLE and may be similar to those related to autoimmune gastrointestinal diseases. OBJECTIVE: Our aim was to search for gastrointestinal organ-specific autoantibodies in 194 patients with systemic lupus and 103 healthy controls from Southern Brazil. Methods Anti-endomysium antibodies (IgA-EmA), anti-gastric parietal cells (GPC) antibodies, anti-smooth muscle antibodies (ASMA), anti-mitochondrial antibodies (AMA) and anti-LKM-1 (liver-kidney microsomal) were searched for using indirect immunofluorescence in the sera of patients and controls. RESULTS: The total positivity of antibodies in SLE patients was 14.4% (28/194) and differed significantly from healthy individuals (0.97%; p<0.001). IgA-EmA was more common in lupus patients than in controls (11/194; p=0.009), and one of these patients had dermatitis herpetiformis. Clinical association revealed that IgA-EmA was more common in SLE patients with discoid lesions. The frequency of anti-GPC (p=0.10), ASMA (p=0.16) and AMA (p=0.55) did not differ significantly between groups. No patient presented LKM-1 autoantibodies. One patient presenting anti-GPC was diagnosed with atrophic gastritis and pernicious anemia. CONCLUSION: Only IgA-EmA was significantly associated with lupus and with the presence of discoid lesions. Until now, no obvious association with celiac disease has been found.

Antinucleosome in systemic lupus erythematosus. A study in a Brazilian population.

Antinucleosome antibodies have been found with variable prevalence in systemic lupus erythematosus (SLE) and were associated with more severe disease. This research aims to study the prevalence of antinucleosome antibodies in a sample of Brazilian adult SLE patients and their association with clinical findings and disease activity. Ninety-two adult patients (81 females and 11 males, with mean age of 37.29 ± 10.98 years) with SLE were studied for clinical and antibody profile, disease activity by SLE disease activity index (SLEDAI), and presence of antinucleosome antibodies by ELISA. The prevalence of antinucleosome antibodies was 61.9% (mean titer, 87.8 ± 62.6 U). No relationship was found of antinucleosome presence and any of the studied clinical features. A positive association was detected with anti-DNA (p = 0.001) and SLEDAI (p < 0.0001), but not with anti-Sm, anti-Ro, anti-La, and anti-RNP. No specific disease feature could be associated with the presence of antinucleosome; however, a positive relationship was detected with disease activity measured by SLEDAI and with anti-DNA presence.

Complement factor B allotypes in the susceptibility and severity of coeliac disease in patients and relatives.

The alternative pathway of complement plays an important role in the pathogenesis of coeliac disease (CD), where factor B (BF) is central to its activation. CD is a gluten-sensitive enteropathy that results from a complex interplay between genetic, immunologic, and environmental factors. In this study we evaluated the association of BF allotypes with the susceptibility and severity of CD, and with the presence of autoantibodies. Seventy-six non-related patients (56 female; 20 male; 2-77 years) and 150 first-degree relatives (87 female, 63 male; 2-75 years) were investigated. As controls, 97 healthy individuals were included (67 female;, 30 male; 1-71 years). The BF allotypes were determined by high-voltage agarose gel electrophoresis, followed by specific immunofixation. Disease severity was evaluated by anti-endomisial antibody (IgA-EmA) titres and histological findings of intestinal mucosa, which showed a high correlation (r = 0.8; P < 0.00001) in samples collected simultaneously. IgA-EmA was detected in all CD patients ingesting gluten, and in 13.3% of the relatives. The IgA-EmA, smooth muscle, mitochondrial, liver-kidney microsomal, nuclear, gastric parietal cells, and thyroid microsome antibodies were tested by indirect immunofluorescence. A significant decrease in BF S (P = 0.026) and an increasing tendency in BF SF allotype (P = 0.06) were observed in CD patients when compared to their relatives. On the other hand, BF S frequency was increased (P = 0.001 RR = 2.32) and BF SF (P = 0.002) decreased in the relatives when compared to the controls. No differences were observed in the distribution of BF phenotypes amongst the CD patients and the control group, and no association was found with CD severity or with the presence of autoantibodies. These results suggest BF SF as a CD susceptibility marker, and BF S as a protection marker of the disease amongst CD families in the Brazilian population.

Spectrum of autoantibodies in celiac patients and relatives.

The coexistence of celiac disease together with a range of autoimmune disorders has already been reported. The aims of this study were to perform a broad spectrum of autoantibodies in celiac patients (N = 56), their first-degree relatives (N = 118), and compare the data with healthy controls (N = 101) and patients with inflammatory bowel disease (N = 42; Crohn's disease, N = 18 and ulcerative colitis, N = 24). All serum samples were tested by indirect immunofluorescence to the anti-endomysium antibodies (EmA), anti-neutrophil cytoplasmic (ANCA), anti-smooth-muscle (SMA), anti-mitochondrial (AMA), anti-nuclear (ANA), anti-liver-kidney microsomal (LKM), anti-gastric parietal cells (GPCA), and anti-thyroid microsome (TMA). EmA were detected in 100% of celiac patients ingesting gluten and in 16.1% of the first-degree relatives, while ANCA were positive only in patients with ulcerative colitis (45.6%) and Crohn's disease (16.5%). Fourteen CD patients (25%) were positive for at least one of the other autoantibodies, with significant prevalence of TMA, ANA, and GPCA, while the relatives showed 17.8% of positivity, with an increased prevalence of ANA and TMA. These results emphasize the value of screening for different autoantibodies in celiac patients and their relatives and corroborate the need for evaluation and follow-up of these individuals.

Antiendomysium antibodies in Brazilian patients with celiac disease and their first-degree relatives.

BACKGROUND: Literature data have shown high specificity of antiendomysial antibodies (EmA IgA) in celiac disease. The scarcity of Brazilian reports concerning this subject motivated the present study. OBJECTIVES: To determine the sensitivity and specificity of antiendomysial IgA antibodies in Brazilian celiac patients at diagnosis and after treatment, to confirm patient adherence to a gluten-free diet and to screen first-degree relatives. METHODS: An extensive clinical and serological study was performed by investigating the presence of these antibodies in 392 individuals from Southern Brazil. Indirect immunofluorescence using human umbilical cord as substrate was employed and the total levels of IgA were determined by turbidimetry in all groups. The study was conducted on 57 celiac patients (18 at diagnosis, 24 who adhered to a gluten-free diet and 15 with marked or slight transgression of the diet), 115 relatives of celiac patients (39 families), 94 patients with other gastrointestinal diseases, and 126 healthy individuals from the general population. RESULTS: The results demonstrated 100% positivity for the recently diagnosed patients and for those consuming gluten, in contrast to the patients who complied with the diet (0%). In the control group one individual was positive, but refused to undergo a biopsy. In the group of other gastrointestinal diseases, one positive patient presented ulcerative colitis, Down's syndrome and epilepsy, and the intestinal biopsy was diagnostic for celiac disease. These data showed 99.3% specificity for the test. Eighteen relatives were positive for antiendomysial antibodies IgA (15.65%), and comparison with the healthy population revealed a significant difference. An intestinal biopsy was obtained from seven subjects (one with total villous atrophy and six without alterations in the mucosal architecture, but all with a high number of intra-epithelial lymphocytes). CONCLUSIONS: The method revealed 100% sensitivity and 99.3% specificity. Because it is not an invasive method it can be used for the screening of atypical and latent forms of celiac disease to avoid serial biopsies and to control adherence to a gluten-free diet with implications in the prevention of malignancy in celiac disease.

[Autoantibody profile among Kaingang and Guarani tribe Indians in Southern Brazil]. / Perfil de auto-anticorpos em índios das tribos Kaingang e Guarani do Sul do Brasil.

This study investigated the autoantibody profile of 241 blood samples from 176 Kaingang and 65 Guarani Indians from three populations living on the Rio das Cobras and Ivaí reservations, in the state of Paraná, in southern Brazil. The presence of antimitochondrial, anti-smooth muscle, antinuclear, anti-parietal cell, and anti-liver-kidney microsome antibodies was determined by indirect immunofluorescence. These results were compared with samples from 100 healthy Caucasian individuals from the general population of the state. Total positivity was 9% for the indigenous population and 4% for the control population. The prevalence of anti-smooth muscle antibodies was significantly higher among the Guarani and Kaingang individuals from the Rio das Cobras reservation (P = 0.03). It is likely that the increased exposure that these indigenous Brazilians have to infectious diseases that were previously unknown to them comes from more contact with non-native populations, growing acculturation, and cultural practices that include scarification and tattooing. The presence of auto-antibodies in these Brazilian Indians may be related to mechanisms of molecular mimicry with viral or bacterial antigens.

[Comparison of IgA class reticulin and endomysial antibodies for the diagnosis and dietary control in celiac disease]. / Comparação dos anticorpos anti-reticulina e antiendomísio classe IgA para diagnóstico e controle da dieta na doença celíaca.

Sensibility to gluten is a condition with high immunological reaction against gluten proteins from wheat, barley, rye and oats in individuals genetically susceptible. Celiac disease is its most frequent expression with various forms of clinical presentation. The treatment consists in gluten free diet. Although the biopsy of proximal small bowel is necessary, the importance of serological tests is increasing in the screening, diagnosis and monitoring of gluten free diet in celiac patients. The aim of this study was to investigate the presence of antiendomysium (EmA-IgA) and anti-reticulin (ARA-IgA) antibodies in 56 celiac patients (17 at diagnosis, 24 adherent to the diet and 15 with transgression to the diet). The antibodies were detected by indirect immunofluorescence, using human umbilical cord as substrate for the EmA-IgA and rat liver and kidney for the ARA-IgA. In the patients at diagnosis and in the group with transgression to the diet the total positivity was 100% for EmA-IgA and 59.4% for ARA-IgA. Antibodies were not detected in gluten-free diet patients. Among the 32 positive patients, the concordance of both tests was of 59.4% (19/32), being 40.6% (13/32) negative to ARA-IgA and positive to EmA-IgA. No patient was positive for ARA-IgA and negative for EmA-IgA. Thus, the sensitivity for EmA-IgA was of 100% and 59.4% for ARA-IgA. The association of the two tests did not improve the positivity in the samples. In conclusion, EmA-IgA can be considered the best serological test for diagnosis and follow up of celiac patients, because it presents high predictive value, high specificity and sensibility and is not expensive if using human umbilical cord as substrate.

Paciente com olho seco pós-transplante de medula óssea: relato de caso / Dry eye after bone marrow transplantation

Os autores descrevem um caso de olho seco pós-transplante de medula óssea associado a lesäo corneana peresistente. Discutem a possibilidade de correlaçäo entre os achados de auto-anticorpos séricos contra constituintes celulares de córnea e conjuntiva presentes neste paciente, e a patogênese da ceratoconjuntivite sicca pós-transplante de medula óssea

Clinical, autoimmune and demographic profile in systemic lupus erythematosus (SLE) patients from southern Brazil.

With the purpose of determining the association of clinical, autoimmune and demographic features, a group of 90 SLE patients from Southern Brazil were investigated. At diagnosis, 24% of them were under 20 years, 63% were between 20 and 40 years and 13% were older than 40 years. According to the ethnic background, there were 66% Brazilian-white patients, 21% Caucasians and 13% Mullatos/Blacks. Antinuclear antibodies (ANA) were present in 98%, anti-ds-DNA in 56% and anti-Sm in 31% of the patients. Anti-ds-DNA were more prevalent in the Caucasians (79%), while anti-Sm were increased in the Mullatos/Blacks (58%, p < 0.02) as compared to the white patients (Brazilian-whites = 22% and Caucasians = 42%). Neurologic involvement had lower prevalence in the group of Mullato/Black patients (8%) than in the Brazilian-whites (32%) and Caucasians (31%). Serositis was present in 51% of the Brazilian-whites, in 21% of the Caucasians and in 41% of the Mullatos/Blacks. On the other hand, the Mullato/ Black group had an increased prevalence of vasculitis (50%) and none of them presented with Raynaud's phenomenon. Younger patients at diagnosis presented higher frequency of renal involvement (p < 0.05), anti-ds-DNA positivity (p < 0.02) and more severe disease (p < 0.07), and in those patients diagnosed after age 40, 33% presented with Raynaud's phenomenon (p < 0.05). Regarding the anti-ds-DNA positivity, 78% of the patients had renal involvement (p < 0.01 RR 2.2) and 66% severe disease (p < 0.05). These results might be important in assessing clinical subsets and may aid individualized management of Brazilian SLE patients. Also, they may corroborate the need for special attention to racial composition in clinical and immunogenetic studies.

Investigação de auto-anticorpos em doenças da tireóide - correlação entre os métodos de imunofluorescência indireta, aglutinação passiva e IRMA / Investigation of autoantibodies in thyroid diseases - correlation among indirect immunofluorescence, passive agglutination and IRMA

Os auto-anticorpos anti tireoglobulina (AAT) e antimicrossomal/peroxidase (AAM) estão altamente associados às doenças auto-imunes da tireóide e tem sido investigados por métodos diversos. O presente estudo foi realizado em um grupo de 108 pacientes oom doença da tireóide (Tireoidite de Hashimoto, n = 43; Doença de Graves - n = 13 e Bócio colóide - n = 52) e em 25 doadores sadios de banco de sangue do Hospital de Clínicas - UFPR. Os anticorpos AAM e AAT foram analisados simultaneamente pelo métodos de Aglutinação Passiva (AP), IRMA e Imunofluorescência Indireta (IFI) com o objetivo de padronizar este último em nosso serviço e compará-lo com os demais. A positividade para os AAM na Tireoidite de Hashimoto, na Doença de Graves e no Bócio colóide variou de 62,8% a 81,4%, 76,8% a 92,3% e 5,76% 19,2%, respectivamente. O coeficiente de relação dos níveis de anticorpos detectados pelos três métodos ressaltou alta significância(AAT,r=0,60 a 0,74 e AAM r=0,84 a 0,91; p< 0,01). A análise dos resultados evidenciou que embora para os AAM a IFI tenha apresentado sensibilidade ligeiramente inferior aos outros métodos, seu uso traria resultados mais confiáveis no laboratório clínico,com grande redução no custo da análise.