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.

Rheumatic manifestations in brazilian patients with AIDS.

INTRODUCTION: Patients with AIDS (acquired immunodeficiency syndrome) may have rheumatic complaints such as arthritis and arthralgia, dry eyes, increased salivary glands, lower back pain, enthesitis etc. Autoantibodies like ANA (antinuclear antibody) and RF (rheumatoid factor) may also be present. OBJECTIVE: To study the prevalence of rheumatic complaints in AIDS patients and correlate them with the presence of ANA and RF. METHODS: We studied 69 patients with AIDS (28.9% women and 71.0% men) with a mean age of 40.8 ± 8.9 years, median disease duration of 60 months, for rheumatic complaints, ANA, ENA-6 (anti-Ro, anti-La, anti-Sm, anti-RNP, anti-Scl70 and anti-Jo1) and RF. We collected demographic data, CD4+ and CD8+ cell count and values of viral load. RESULTS: Arthralgia was present in 39.1%, sicca symptoms in 21.7%, inflammatory lumbar pain in 13.4%, enthesopathy in 6.6%, parotid enlargement in 1.4%, RF in 10.1% and ANA in 8.6%. All patients were negative for ENA-6. ANA was more common in older patients (p = 0.03) and in those with higher viral load (p = 0.006). No association was found with the presence of RF. CONCLUSIONS: The most common manifestation in this context was arthralgia. ANA presence was associated with age of the patients and viral load.

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.

Circulating levels of mannan-binding lectin (MBL) and MBL-associated serine protease 2 in endemic pemphigus foliaceus.

Endemic pemphigus foliaceus (EPF) is an autoimmune disease, which occurs in Brazil and other regions of South America. Mannose-binding lectin (MBL) and MBL-associated serine protease (MASP-2) play a key role in innate immunity, and its deficiency has been related to increased susceptibility to infection and autoimmune diseases. MBL and MASP-2 serum levels were measured in 114 patients with EPF and in 100 healthy individuals in Brazil. MBL and MASP-2 levels were measured by sandwich assays (time-resolved immunofluorimetic assay) using monoclonal antibodies. No difference was observed in the MBL level in patients with EPF compared with controls [mean +/- SEM 1230.07 +/- 132.18 ng/mL (median 789.0 ng/mL) vs. 1036.98 +/- 117.99 ng/mL (median 559.5 ng/mL), P = 0.32]. Non-significant lower MASP-2 levels were observed in EPF [274.34 +/- 15.66 ng/mL (median 239.5 ng/mL ) vs. 304.72 +/- 15.28 ng/mL [median 261.0 ng/mL ), P = 0.06]. MBL deficiency (< 10 ng/mL) or MASP-2 deficiency (< 100 ng/mL) did not differ significantly between patients and controls. These data indicate that MBL and MASP-2 deficiency are not associated with susceptibility to EPF.

Complement activation in infective endocarditis: correlation with extracardiac manifestations and prognosis.

In an infectious process complement activation is necessary for a proper immune and inflammatory response, but when exacerbated may cause tissue injuries. In infective endocarditis (IE) patients tend to develop high titres of circulating immune complexes (CIC) that activate complement. The aim of this study was to evaluate for the first time complement activation in IE for possible correlation with extracardiac manifestations and clinical prognosis. Twenty patients with IE, 14 healthy controls and 15 patients presenting mitral and aortic valve lesions (with no signs of either infection or other associated diseases), were studied. Plasma levels of C3adesArg, SC5b-9, C1rs-C1Inh and C3b(Bb)P were determined by ELISA and C3d by double decker immunoelectrophoresis. C3 and C4 levels were assayed by turbidimetry and CIC by ELISA. Elevation of plasma levels of all complement activation products, with the exception of C3b(Bb)P, indicated a significant classical pathway activation in IE patients when compared to controls (C3d: P < 0.00004; C3adesArg: P < 0.03, SC5b-9: P < 0.01, C1rs-C1Inh: P < 0.00007). CIC levels were significantly increased (P < 0.005) and C3 reduced in IE patients (P < 0.05). Elevated C3d (P < 0.02) and C3adesArg (P < 0.03) levels were associated with pulmonary manifestations. In addition, C3d was significantly elevated in the patients who died when compared to those who had a good recovery (P < 0.02). Our data demonstrate the activation of the complement classical pathway, most probably mediated by CIC, in IE and suggests C3d and C3adesArg as possible markers for extracardiac lesion and severity of the disease.

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.

Complement activation in Brazilian patients with preeclampsia.

The aim of this study was to evaluate the complement activation in Brazilian patients with preeclampsia and to correlate it with the severity and clinical outcome of the disease. Plasma levels of C3d, SC5b-9, C3 and C4 were measured in 16 patients with preeclampsia and in 17 normotensive pregnant women. Ten patients developed severe and six mild disease. C3 and C4 levels were determined by turbidimetry using polyclonal specific antisera. C3d concentrations were evaluated through double-decker rocket immunoelectrophoresis and SC5b-9 was assayed by a double-antibody enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody against a neoantigen expressed in the formed complex. The mean levels of all variables were significantly higher in the preeclamptic group (before the delivery) when compared to the normal pregnancies. The complex SC5b-9 followed by C3d showed the most significant results for those comparisons (p < or = 0.00001). The levels of all parameters in the preeclampsia patients decreased significantly after the delivery. Again, the complex SC5b-9 and C3d showed the most significant results (p < or = 0.0004). None of the studied variables showed statistically significant differences regarding the severity of preeclampsia. These results confirm the activation of complement in preeclampsia, suggesting that this activation is related to the disease manifestation. Our findings further emphasize the involvement of complement activation in the pathological manifestations of preeclampsia.

[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.

SC5b-9 is the most sensitive marker in assessing disease activity in Brazilian SLE patients.

This study investigated whether increased plasma levels of terminal complement complex (SC5b-9) or split products correlate with disease activity and clinical manifestations in Brazilian systemic lupus erythematosus (SLE) patients. Comparisons with conventional measurements of complement and other inflammatory markers were also performed. Plasma levels of SC5b-9, C3a desArg, C1rs-C1Inhibitor, C3b(Bb)P, C3, C4, erythrocyte sedimentation rate (ESR) and mucoproteins (MP) were measured in 41 patients with SLE of different disease activity: 10 patients with none, 15 patients with mild, and 16 patients with moderate or severe activity. All parameters, with the exception of C3 and C3b(Bb)P, showed a statistically significant correlation with disease activity. Plasma levels of SC5b-9, C3a desArg, C4, CH50, ESR and MP revealed significant differences between the groups of patients without activity and those with moderate or severe disease. Although none of the variables were able to discriminate between patients without and those with mild activity, SC5b-9, C3a desArg, C4, ESR and mucoproteins showed significant differences between the patients with mild and those with moderate or severe disease. Among all the variables, SC5b-9 levels showed the most significant results and correlated well with the severity of the disease (p < 0.0005). Our data suggest that elevated levels of complement activation products, particularly of SC5b-9 are more sensitive markers in assessing disease activity than conventional laboratory diagnosis. Modern complement diagnosis is therefore recommended for monitoring disease progress in SLE patients.

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.