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Browsing MED - Artigos publicados em revistas indexadas by Author "Alves, JD"
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- Antibodies against HDL Components in Ischaemic Stroke and Coronary Artery DiseasePublication . Batuca, J; Amaral, M; Favas, C; Justino, G; Papoila, A; Ames, P; Alves, JDQuantitative and qualitative defects of high-density lipoprotein (HDL) are important in atherogenesis. In this study, we investigated whether antibodies against HDL components had additional value to conventional cardiovascular risk factors for the diagnosis of ischaemic stroke (IS) and coronary artery disease (CAD). Cross-sectional study was conducted on 53 patients with IS, 51 with CAD and 55 healthy controls, and in vitro studies to validate findings of the clinical study. We determined serum immunoglobulin G (IgG) antibodies against HDL (aHDL), apolipoproteins (aApoA-I, aApoA-II and aApoC-I) and paraoxonase-1 (aPON1) as well as PON1 activity (PON1a), total antioxidant capacity and biomarkers of endothelial activation (serum nitric oxide metabolites, 3-nitrotyrosine, VCAM-1 and ICAM-1); in vitro assays tested the capacity of IgG aHDL purified from high titer patients to inhibit PON1a and to reverse protective effect of HDL on endothelial cells. IgG aHDL, aApoA-I and aPON1 were higher in IS and CAD than controls (p < 0.001), predicted negatively PON1a and positively VCAM-1 and ICAM-1. By adding IgG aHDL and aApoA-I to a traditional cardiovascular risk factors model for IS and by adding IgG aHDL in a similar model for CAD, we obtained better discrimination of IS and CAD from healthy controls. IgG aHDL purified from IS and CAD inhibited PON1a by 38% (p < 0.01) and abrogated the protective effect of HDL on VCAM-1 expression by 126% compared with non-specific human IgG (p < 0.001). IgG against HDL components interfere with the antioxidant and anti-inflammatory properties of HDL and may represent novel biomarkers for vascular disease that need to be investigated in prospective studies.
- Antibodies towards high-density lipoprotein components in patients with psoriasisPublication . Paiva-Lopes, MJ; Batuca, J; Gouveia, S; Alves, M; Papoila, AL; Alves, JDPsoriasis is a chronic inflammatory immune disorder associated with an increased risk of atherosclerosis. This increased risk is not fully understood. High-density lipoproteins (HDL) play an important role in the prevention of atherosclerosis and any factors that may hamper HDL function such as anti-HDL antibodies (aHDL) might be associated with an increased cardiovascular risk. We aimed to determine whether anti-HDL antibodies (aHDL) are present in patients with psoriasis. Sixty-seven patients with psoriasis were compared with a healthy control group. Epidemiologic and clinical data were recorded. IgG and IgM aHDL, IgG anti-apolipoprotein A-I (aApoA-I), anti-apolipoprotein E (aApoE), and anti-paraoxonase 1 (aPON1) antibodies, as well as VCAM-1, IL-6, and TNF-α were assessed by ELISA. Apolipoprotein A-I (ApoA-I) and Apolipoprotein E (ApoE) were measured by immunoturbidimetric immunoassay. Patients with psoriasis had higher titers of IgG aHDL (p < 0.001), IgG aApoA-I (p = 0.001) and aApoE antibodies (p < 0.001). IgG aHDL and aApoE titers were higher in patients with severe psoriasis (p = 0.010 and p = 0.018, respectively). Multiple regression analysis, considering all clinical and biological variables, showed that aApoE, IL-6, and aPON1 are the biological variables that best explain aHDL variability. This is the first report showing the presence of aHDL, aApoA-I, and aApoE antibodies in patients with psoriasis. These antibodies were associated with increased disease severity and may contribute to the pathogenesis of atherosclerosis in psoriasis. They may fulfill the clinical need for biomarkers of cardiovascular risk associated with psoriasis that would help to stratify patients for prevention and therapeutic approaches.
- Changes in Iron Metabolism Induced by Anti-Interleukin-6 Receptor Monoclonal Antibody are Associated with an Increased Risk of InfectionPublication . Ribeiro, R; Batista, F; Paula, F; Alves, JD(1) Background: Treatment of patients with rheumatoid arthritis (RA) with an anti-IL-6 receptor (anti-IL-6R) monoclonal antibody (tocilizumab) has been found to influence iron metabolism. The objective of the present study was to ascertain whether changes in iron metabolism induced by anti-IL-6R biologic therapy were independently associated with an increased infection risk. (2) Methods: A prospective longitudinal study of patients with RA treated with tocilizumab was conducted. RA patients treated with an antitumor necrosis factor α monoclonal antibody were also included as a control group. The primary outcome was occurrence of infection during the first 24 months of biologic therapy. (3) Results: A total of 15 patients were included, with a mean age of 51.0 ± 4,1 and 73.3% (n = 11) female. A multivariate survival regression model, adjusted for confounding factors, was fitted for each of the iron metabolism variables. Hazard ratios for being above the median of each parameter was considered. Transferrin saturation above the median value (>32.1%) was associated with a higher infection risk (HR 4.3; 95%CI 1.0-19.69; p = 0.05). Similarly, although non-significantly, higher serum iron was strongly associated with infection occurrence. (4) Conclusions: This study identified a probable association between infection risk and higher serum iron and transferrin saturation in patients with RA on anti-IL-6R biologic therapy. We suggest that both these parameters should be considered relevant contributing factors for infection occurrence in patients on anti-IL-6R therapy.
- Connective tissue disease-associated interstitial lung diseasePublication . Oliveira, RP; Ribeiro, R; Melo, L; Grima, B; Oliveira, S; Alves, JDBACKGROUND: Connective tissue diseases (CTD) are frequently associated with interstitial lung disease (ILD), significantly impacting their morbidity and mortality. AIM: Analyze the experience of an autoimmune specialized unit on treating CTD-ILD and characterize the population based on most frequent diseases, imaging patterns, lung function tests results, serology and treatment. Assess mortality and mortality predictors in these patients. METHODS: Retrospective, descriptive and statistical analysis of the CTD-ILD patients followed up at an autoimmune diseases unit during a 6-year period. RESULTS: Over the study period, 75 patients with CTD-ILD were treated with a mean follow-up of 49 ± 31 months. The most frequent CTD were systemic sclerosis and rheumatoid arthritis. ILD was diagnosed prior to CTD in 8% of patients and concomitantly in 35%. Nonspecific interstitial pneumonia was the CT pattern in 60% and 35% had an isolated diminished DLCO on lung function tests. Pulmonary hypertension was present in 12% and it was the single most important mortality predictor (OR 14.41, p = 0.006). Corticosteroids are the mainstay of treatment but biologics were prescribed in 39% of the patients (mostly tocilizumab and rituximab). Two scleroderma patients were recently treated with nintedanib. CONCLUSIONS: ILD is a potential complication of every CTD and can impose a dramatic burden on these patients. The clinical relevance of ILD together with their early expression in the course of the disease underlines the importance of the presence of chest physicians in these units.
- Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study.Publication . Amengual, O; Forastiero R, R; Sugiura-Ogasawara, M; Otomo, K; Oku, K; Favas, C; Alves, JD; Žigon, P; Ambrožič, A; Tomšič, M; Ruiz-Arruza, I; Ruiz-Irastorza, G; Bertolaccini, ML; Norman, GL; Shums, Z; Arai, J; Murashima, A; Tebo, AE; Gerosa, M; Meroni, PL; Rodriguez-Pintó, I; Cervera, R; Swadzba, J; Musial, J; Atsumi, TOBJECTIVE: A task force of scientists at the International Congress on Antiphospholipid Antibodies recognized that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) might contribute to a better identification of antiphospholipid syndrome (APS). Accordingly, initial and replication retrospective, cross-sectional multicentre studies were conducted to ascertain the value of aPS/PT for APS diagnosis. METHODS: In the initial study (eight centres, seven countries), clinical/laboratory data were retrospectively collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics (Inova) using two ELISA kits. A replication study (five centres, five countries) was carried out afterwards. RESULTS: In the initial study (n = 247), a moderate agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed (k = 0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those without (9%), OR 10.8, 95% CI (4.0-29.3), p < 0.0001. Sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio of IgG aPS/PT for APS diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study (n = 214), a moderate/substantial agreement between the IgG aPS/PT results obtained with both ELISA kits was observed (k = 0.630). IgG aPS/PT were more prevalent in APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6-16), p < 0.0001. Sensitivity, specificity, LR + and LR- for APS diagnosis were 47%, 88%, 3.9 and 0.6, respectively. CONCLUSIONS: IgG aPS/PT detection is an easily performed laboratory parameter that might contribute to a better and more complete identification of patients with APS.
- Extended Release-Niacin increases anti-ApoA-I antibodies that block the anti-oxidant effect of HDL-C: the EXPLORE clinical trial.Publication . Batuca, JR; Amaral, M; Favas, C; Paula, F; AMES, PR; Papoila, AL; Alves, JDExtended Release-Niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I). METHODS: Twenty-one patients older than 18 years, with HDL-C ≤ 40 mg/dL (men) or ≤ 50 mg/dL (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42. RESULTS: The effect of ERN on PON1 activity was non-significant (coefficient estimate 20.83U/L, 95% CI -9.88 to 51.53; p = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg/dL, 95% CI 1.16 to 9.25; p = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg/dL, 95% CI 0.57 to 4.34; p = 0.011) and HDL3 (coefficient estimate 2.73 mg/dL, 95% CI 0.47 to 4.98; p = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 µg/mL, 95% CI 0.09-0.40; p = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity. CONCLUSIONS: The rise in HDL-C achieved with ERN was not matched by improved anti-oxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.
- Factors implicated in the generation and persistence of long-lived plasma cell-mediated autoimmunityPublication . Neves, M; Alves, JDAutoimmune diseases are frequently associated with the production of autoantibodies by cells that escaped the protective mechanisms that control self-tolerance. Some of these cells develop into long-lived plasma cells which are predominantly located in the bone marrow. The generation of this particular type of cell requires specific migration, differentiation, and survival signals. The identification of some of the factors involved in these pathways has permitted the development of specific therapeutic approaches and may even provide investigators with further new therapeutic targets, particularly in autoimmune diseases associated with persistent autoantibody production. We reviewed the existing evidence for the mechanisms implicated in the perpetuation of long-lived plasma cells and the most recent therapeutic proposals in this context.
- Persistency of low levels of anticardiolipin and anti-beta2 glycoprotein1 in thrombosisPublication . Amaral, M; Favas, C; Alves, JDBACKGROUND: Antiphospholipid antibodies, the hallmark of the antiphospholipid syndrome, are associated with both venous and arterial thrombosis. Despite some reports stating that this association may be present in patients with low titres of anticardiolipin antibodies, a clear association has only been established in the presence of a moderate to high concentrations (above 40 GPL or MPL). METHODS: In order to study whether low antibody titres could be associated with thrombosis, we reviewed the files of 196 patients, 94 with and 102 without thrombotic events, for a period of 4.4 and 5.1 years respectively. Files from patients with persistent low titres of antiphospholipid antibodies recorded in the unit database were selected, independently of the associated clinical history or diagnosis. Epidemiology, clinical and treatment information were collected and the serum variability of the antibody titres was analysed in relation to the presence of thrombotic events. RESULTS: Thrombotic events were classified as venous 81.9% and arterial 18.1%. 23/94 (24.5%) patients with thrombosis had miscarriages. There were no significant differences between serum concentrations of antiphospholipid antibodies in the thrombotic and non-thrombotic groups. However, there was a higher consistency of the antibody concentrations in patients with thrombosis, as seen by the significantly lower variability of IgG aCL and abeta2GP1 titres in patients with thrombosis when compared to non-thrombotic controls (p=0.0025 and p<0.0001, respectively). CONCLUSION: Consistency of low titres of antiphospholipid antibody levels may be associated with a higher risk of thrombotic events overall.
- Psoriasis-associated vascular disease: the role of HDL.Publication . Paiva-Lopes, MJ; Alves, JDPsoriasis is a chronic inflammatory systemic disease with a prevalence of 2-3%. Overwhelming evidence show an epidemiological association between psoriasis, cardiovascular disease and atherosclerosis. Cardiovascular disease is the most frequent cause of death in patients with severe psoriasis. Several cardiovascular disease classical risk factors are also increased in psoriasis but the psoriasis-associated risk persists after adjusting for other risk factors.Investigation has focused on finding explanations for these epidemiological data. Several studies have demonstrated significant lipid metabolism and HDL composition and function alterations in psoriatic patients. Altered HDL function is clearly one of the mechanisms involved, as these particles are of the utmost importance in atherosclerosis defense. Recent data indicate that biologic therapy can reverse both structural and functional HDL alterations in psoriasis, reinforcing their therapeutic potential.
- Stress-related mucosal disease: incidence of bleeding and the role of omeprazole in its prophylaxisPublication . Amaral, M; Favas, C; Alves, JD; Riso, N; Riscado, MBACKGROUND: Upper gastrointestinal bleeding is the severe complication of stress-related mucosal disease in hospitalized patients. In intensive care units (ICU), risk factors are well defined and only mechanical ventilation and coagulopathy proved to be relevant for significant bleeding. On the contrary, in non-ICU settings there is no consensus about this issue. Nevertheless, omeprazole is still widely used in prophylaxis of bleeding. The objective of our study was to evaluate the relevance of stress-related mucosal disease bleeding in patients admitted to an internal medicine ward, and the role of omeprazole in its prophylaxis. METHODS: We conducted a retrospective study in which we analysed consecutive patients who were admitted to our ward over a year. We recorded demographic characteristics of the patients, potential risk factors for stress-related mucosal disease (clinical data, laboratory, and medication), administration of prophylactic omeprazole, and total cost of this prophylaxis. Patients with active gastrointestinal bleeding on the admission were excluded. We recorded every upper gastrointestinal bleeding event with clinical relevance. RESULTS: Five hundred and thirty-five patients, mean age 70 years, mean length of stay 9.6+/-7.7 days; 140 (26.2%) patients were treated with 40 mg of omeprazole intravenously, 193 (36.1%) with 20mg of omeprazole orally, and 202 (37.8%) patients had no prophylaxis. There was only one episode (0.2%) of clinically relevant bleeding. CONCLUSION: In patients admitted to an internal medicine ward, incidence of upper gastrointestinal bleeding as a complication of stress-related mucosal disease is low. We found that there is no advantage in prophylaxis with omeprazole