Lack of Antilipoprotein Lipase Antibodies in Takayasu's Arteritis

Background. Antilipoprotein lipase (anti-LPL) antibodies were described in rheumatic diseases. In systemic lupus erythematosus they were highly associated with inflammatory markers and dyslipidemia, and may ultimately contribute to vascular damage. The relevance of this association in Takayasu's arteritis, which is characterized by major inflammatory process affecting vessels, has not been determined. Objectives. To analyze the presence of anti-LPL antibodies in patients with Takayasu's arteritis and its association with inflammatory markers and lipoprotein risk levels. Methods. Thirty sera from patients with Takayasu's arteritis, according to ACR criteria, were consecutively included. IgG anti-LPL was detected by a standard ELISA. Lipoprotein risk levels were evaluated according to NCEP/ATPIII. Inflammatory markers included ESR and CRP values. Results. Takayasu's arteritis patients had a mean age of 34 years old and all were females. Half of the patients presented high ESR and 60% elevated CRP. Lipoprotein NCEP risk levels were observed in approximately half of the patients: 53% for total cholesterol, 43% for triglycerides, 16% for HDL-c and 47% for LDL-c. In spite of the high frequency of dyslipidemia and inflammatory markers in these patients no anti-LPL were detected. Conclusions. The lack of anti-LPL antibodies in Takayasu's disease implies distinct mechanisms underlying dyslipidemia compared to systemic lupus erythematosus

Longitudinal fluctuation of anti-lipoprotein lipase antibody is related with disease activity in systemic lupus erythematosus patients without anti-dsDNA antibodies

INTRODUÇÃO: O Lúpus Eritematoso Sistêmico (LES) se caracteriza por períodos de exacerbação e remissão clínica que frequentemente são acompanhados por alterações nos níveis séricos de anticorpos específicos, como o anti-dsDNA, que está presente em 40% dos casos, associado principalmente à atividade renal. Recentemente houve a descrição de duas subpopulações de anticorpos antilipoproteína lipase (anti-LPL) no LES: uma com e a outra sem atividade anti-dsDNA. A possível relação desse último grupo de anticorpos com a atividade inflamatória de doença ainda não foi analisada no LES. OBJETIVOS: Avaliar longitudinalmente a associação dos níveis séricos dos anticorpos anti-LPL com atividade do LES em pacientes com anti-dsDNA persistentemente negativo. PACIENTES E MÉTODOS: Cinco pacientes com LES com anti-dsDNA persistentemente negativo mensurado por ELISA e por imunofluorescência indireta em crithidia luciliae e altos títulos de anti-LPL por ELISA (> 5 desvios-padrão (DP) da média de 20 controles normais) foram selecionados e acompanhados longitudinalmente durante um período mínimo de dois anos. RESULTADOS: Caso 1: Homem, 24 anos com LES desde 2001 apresentou hemorragia alveolar, proteinúria, hipertensão arterial sistêmica, eritema malar, aftas, artrite, FAN+, com SLEDAI (systemic lupus erythematosus disease activity index) = 16 e anti-LPL = 144UA. Tratado com pulso de metilprednisolona e prednisona com melhora clínica e SLEDAI = 0 e redução do anti-LPL (109UA). Nova atividade com acometimento renal em abril de 2002, SLEDAI = 10 e aumento de anti-LPL (150UA). Iniciada pulsoterapia de ciclofosfamida e metilprednisolona com boa resposta, SLEDAI = 0 e diminuição de anti-LPL (77UA) até a sua total negativação acompanhando a remissão do quadro no ano de 2003. Caso 2: Mulher, 32 anos, com LES desde 1997. Em setembro de 2001 iniciou vasculite cutânea, febre e rash, SLEDAI = 10, anti-LPL = 80UA. Em janeiro de 2002, teve atividade renal e HAS, SLEDAI = 8 e anti-LPL = 25UA, mas com a introdução de CE e ciclofosfamida evoluiu com melhora importante. Em 2003, assintomática, apresentava SLEDAI = 2 e anti-LPL = 12UA. Caso 3: Homem, 39 anos, com LES desde 1997. Estável em uso de cloroquina, sem atividade durante 3 anos, SLEDAI = 0 em todas as ocasiões e sem variação dos títulos de anti-LPL no período do estudo: 85UA (2001),100UA (2002) e 86UA (2003). Caso 4: Mulher, 58 anos com LES desde 1996. Remissão do LES desde agosto de 2001 e com SLEDAI = 0 no período do estudo. Títulos de anti-LPL sem flutuações significativas: 71UA (2001), 42UA (2002) e 61UA (2003). Caso 5: Mulher, 55 anos com LES desde 1989. Estável desde 2000 em uso de cloroquina, SLEDAI = 0, e títulos de anti-LPL também sem variações: 71UA (1999), 92UA (2001), 71UA (2002) e 90UA (2003). CONCLUSÃO: A avaliação longitudinal dos pacientes selecionados mostrou-se estar associada à flutuação dos títulos de anti-LPL com o SLEDAI, sugerindo ser essa variação um novo marcador de atividade do LES, na ausência de anticorpos anti-dsDNA.INTRODUCTION: Systemic lupus erythematosus (SLE) is characterized by periods of clinical flares and remission that are followed by alterations of sera specific autoantibodies such as anti-dsDNA, present in 40% of the cases and strongly associated with renal involvement. Recently, there was a description of two subpopulations of anti-lipoprotein lipase antibodies (anti-LPL) in SLE: with and without anti-dsDNA activity. A possible relationship between these antibodies with inflammatory activity of SLE was not analyzed. OBJECTIVES: To evaluate longitudinally the association between anti-LPL with lupus activity in patients persistently negatives for anti-dsDNA antibodies. PATIENTS AND METHODS: Five SLE patients with persistently negative anti-dsDNA measured by ELISA and indirect immunofluorescence using crithidia luciliae and high titers of anti-LPL by ELISA (> 5 SD) were selected and followed for at least 2 years. RESULTS: Case 1: A 24-year-old male with SLE since 2001, presented with alveolar hemorrhage, proteinuria, systemic hypertension, malar rash, oral ulcers, polyarthritis, positive ANA, SLEDAI=16 and anti-LPL=144U. He was treated with intravenous (IV) methylprednisolone followed by prednisone and had an excellent response. SLEDAI=0, anti-LPL decreased to 109U. New renal flare in April 2002, SLEDAI=10 and a new increment of anti-LPL (150U). IV Cyclophosphamide and methylprednisolone were started and he achieved remission, SLEDAI=0 and a decrease of anti-LPL (77U) until become negative in 2003. Case 2: A 32-year-old female had SLE since 1997. In September 2001 began cutaneous vasculitis, fever and rash, SLEDAI=10, anti-LPL=80U. In January 2002, she had renal involvement and systemic hypertension, SLEDAI=8 and anti-LPL= 25U. She received corticosteroid and cyclophosphamide and improved. In 2003, she was asymptomatic, SLEDAI=2 and anti-LPL=12U. Case 3: A 39-year-old male has SLE since 1997. He was stable, under chloroquine use, without disease activity for 3 years, SLEDAI=0 in all period studied and no fluctuation of anti-LPL titers: 85U (2001),100U (2002) e 86U (2003). Case 4: A 58-year-old female had SLE since 1996. She was in remission since August 2001 with a SLEDAI=0 during all this study. Anti-LPL titers did not significantly change: 71U (2001), 42U (2002) e 61U (2003). Case 5: A 55-year-old female had SLE since 1989. She was stable since 2000 using chloroquine, SLEDAI=0, and anti-LPL titers without variations: 71U (1999), 92U (2001), 71U (2002) e 90U (2003). CONCLUSION: The longitudinal evaluation of the selected patients showed a positive correlation between the fluctuations of the titers of anti-LPL with the SLEDAI score. These findings suggest that this variation may be a new marker for lupus activity in patients without anti-dsDNA antibodies

Heparin Increases HLA-G Levels in Primary Antiphospholipid Syndrome

Objectives. The aim of this study was to investigate the HLA-G serum levels in Primary Antiphospholipid Syndrome (PAPS) patients, its impact on clinical and laboratory findings, and heparin treatment. Methods. Forty-four PAPS patients were age and gender matched with 43 controls. HLA-G serum levels were measured using an enzyme-linked immunosorbent assay (ELISA). Results. An increase in soluble HLA-G levels was found in patients compared to controls (3.35 (0–22.9) versus 1.1 (0–14), P = 0.017). There were no significant differences in HLA-G levels between patients with and without obstetric events, arterial thrombosis, venous thrombosis, or stroke. Sixty-six percent of patients were being treated with heparin. Interestingly, patients treated with heparin had higher HLA-G levels than ones who were not treated with this medication (5 (0–22.9) versus 1.8 (0–16) ng/mL, P = 0.038). Furthermore, patients on heparin who experienced obstetric events had a trend to increased HLA-G levels compared to patients who were not on heparin and did not have obstetric events (5.8 (0–22.9) versus 2 (0–15.2) ng/mL, P = 0.05). Conclusion. This is the first study to demonstrate that serum HLA-G levels are increased in APS patients. We also demonstrated that heparin increases HLA-G levels and may increase tolerance towards autoantigens

Heparin Increases HLA-G Levels in Primary Antiphospholipid Syndrome

Objectives. The aim of this study was to investigate the HLA-G serum levels in Primary Antiphospholipid Syndrome (PAPS) patients, its impact on clinical and laboratory findings, and heparin treatment. Methods. Forty-four PAPS patients were age and gender matched with 43 controls. HLA-G serum levels were measured using an enzyme-linked immunosorbent assay (ELISA). Results. An increase in soluble HLA-G levels was found in patients compared to controls (3.35 (0–22.9) versus 1.1 (0–14), P = 0.017). There were no significant differences in HLA-G levels between patients with and without obstetric events, arterial thrombosis, venous thrombosis, or stroke. Sixty-six percent of patients were being treated with heparin. Interestingly, patients treated with heparin had higher HLA-G levels than ones who were not treated with this medication (5 (0–22.9) versus 1.8 (0–16) ng/mL, P = 0.038). Furthermore, patients on heparin who experienced obstetric events had a trend to increased HLA-G levels compared to patients who were not on heparin and did not have obstetric events (5.8 (0–22.9) versus 2 (0–15.2) ng/mL, P = 0.05). Conclusion. This is the first study to demonstrate that serum HLA-G levels are increased in APS patients. We also demonstrated that heparin increases HLA-G levels and may increase tolerance towards autoantigens

Infliximab Induces Increase in Triglyceride Levels in Psoriatic Arthritis Patients

Objectives. To evaluate lipid profile changes after anti-TNF therapy in patients with psoriatic arthritis (PsA). Methods. Fifteen PsA patients (eight polyarticular, four oligoarticular, two axial, and one mutilating) under infliximab were included. None had dyslipoproteinemia or previous statin use. Total cholesterol (TC) and its fractions, inflammatory markers, and prednisone use were evaluated. Results. The comparisons of lipid levels between baseline and after three months (3M) of anti-TNF therapy showed that there was a significant increase in mean triglycerides (117.8 ± 49.7 versus 140.1 ± 64.1 mg/dL, P = 0.028) and VLDL-c (23.6 ± 10.5 versus 28.4 ± 13.7 mg/dL, P = 0.019) levels. In contrast, there were no differences in the mean TC (P = 0.28), LDL-c (P = 0.42), and HDL-c (P = 0.26) levels. Analysis of the frequencies of each lipid alteration at baseline and at 3M were alike (P > 0.05). Positive correlations were found between VLDL-c and CRP (r = 0.647, P = 0.009) and between triglycerides and CRP (r = 0.604, P = 0.017) levels at 3M. ESR reduction was observed after 3M (P = 0.04). Mean prednisone dose remained stable at beginning and at 3M (P = 0.37). Conclusion. This study demonstrated that anti-TNF may increase TG and VLDL-c levels in PsA patients after three months

Cardiac autonomic impairment and chronotropic incompetence in fibromyalgia

Abstract\ud \ud \ud \ud Introduction\ud \ud We aimed to gather knowledge on the cardiac autonomic modulation in patients with fibromyalgia (FM) in response to exercise and to investigate whether this population suffers from chronotropic incompetence (CI).\ud \ud \ud \ud Methods\ud \ud Fourteen women with FM (age: 46 ± 3 years; body mass index (BMI): 26.6 ± 1.4 kg/m2) and 14 gender-, BMI- (25.4 ± 1.3 kg/m2), and age-matched (age: 41 ± 4 years) healthy individuals (CTRL) took part in this cross-sectional study. A treadmill cardiorespiratory test was performed and heart-rate (HR) response during exercise was evaluated by the chronotropic reserve. HR recovery (deltaHRR) was defined as the difference between HR at peak exercise and at both first (deltaHRR1) and second (deltaHRR2) minutes after the exercise test.\ud \ud \ud \ud Results\ud \ud FM patients presented lower maximal oxygen consumption (VO2 max) when compared with healthy subjects (22 ± 1 versus CTRL: 32 ± 2 mL/kg/minute, respectively; P < 0.001). Additionally, FM patients presented lower chronotropic reserve (72.5 ± 5 versus CTRL: 106.1 ± 6, P < 0.001), deltaHRR1 (24.5 ± 3 versus CTRL: 32.6 ± 2, P = 0.059) and deltaHRR2 (34.3 ± 4 versus CTRL: 50.8 ± 3, P = 0.002) than their healthy peers. The prevalence of CI was 57.1% among patients with FM.\ud \ud \ud \ud Conclusions\ud \ud Patients with FM who undertook a graded exercise test may present CI and delayed HR recovery, both being indicative of cardiac autonomic impairment and higher risk of cardiovascular events and mortality.This work was supported by the Fundação de Amparo a Pesquisa do Estado de São Paulo (Grant 2009/51897-5)

Consensus of systemic lupus erythematosus

Universidade de São Paulo Faculdade de MedicinaHospital Heliópolis de São Paulo Serviços de Clínicas MédicasUniversidade Federal do Rio Grande do Sul Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de Goiás Faculdade de MedicinaUniversidade Federal de Santa Catarina Hospital UniversitárioUniversidade Federal de Minas Gerais Faculdade de MedicinaSanta Casa de Belo Horizonte Clínica ReumatológicaUniversidade Estadual de Campinas Faculdade de Ciências MédicasUSP da Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP)UNIFESP, EPMUNIFESPSciEL

Intestinal microsporidiosis: a hidden risk in rheumatic disease patients undergoing anti-tumor necrosis factor therapy combined with disease-modifying anti-rheumatic drugs?

OBJECTIVE: Immunosuppressed patients are at risk of microsporidiosis, and this parasitosis has an increased rate of dissemination in this population. Our objective was to evaluate the presence of microsporidiosis and other intestinal parasites in rheumatic disease patients undergoing anti-tumor necrosis factor/disease-modifying anti-rheumatic drug treatment. METHODS: Ninety-eight patients (47 with rheumatoid arthritis, 31 with ankylosing spondylitis and 11 with psoriatic arthritis) and 92 healthy control patients were enrolled in the study. Three stool samples and cultures were collected from each subject. RESULTS: The frequency of microsporidia was significantly higher in rheumatic disease patients than in control subjects (36 vs. 4%, respectively; p<0.0001), as well as in those with rheumatic diseases (32 vs. 4%, respectively; p<0.0001), ankylosing spondylitis (45 vs. 4%, respectively; p<0.0001) and psoriatic arthritis (40 vs. 4%, respectively; p<0.0001), despite a similar social-economic class distribution in both the patient and control groups (p = 0.1153). Of note, concomitant fecal leukocytes were observed in the majority of the microsporidia-positive patients (79.5%). Approximately 80% of the patients had gastrointestinal symptoms, such as diarrhea (26%), abdominal pain (31%) and weight loss (5%), although the frequencies of these symptoms were comparable in patients with and without this infection (p&gt;0.05). Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis disease activity parameters were comparable in both groups (p&gt;0.05). The duration of anti-tumor necrosis factor/disease-modifying anti-rheumatic drugs and glucocorticoid use were also similar in both groups. CONCLUSION: We have documented that microsporidiosis with intestinal mucosa disruption is frequent in patients undergoing concomitant anti-tumor necrosis factor/disease-modifying anti-rheumatic drug therapy. Impaired host defenses due to the combination of the underlying disease and the immunosuppressive therapy is the most likely explanation for this finding, and this increased susceptibility reinforces the need for the investigation of microsporidia and implementation of treatment strategies in this population.FAPESPCNPQFederico FoundationWyet