Metabolic syndrome in Sjögren's syndrome patients: a relevant concern for clinical monitoring.

Metabolic syndrome (MetS) has been described in autoimmune diseases. However, there are scarce data about MetS and adipocytokine profile in primary Sjögren's syndrome (pSS). Seventy-one female pSS patients (American-European Consensus Group Criteria, 2002) aged 18-65 years and 71 age-, race-matched control women were enrolled in this case-control study. Clinical data were collected by a standardized protocol. Blood levels of glucose, cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, interleukin-1beta (IL-1beta)/IL-6, B-cell activating factor (BAFF), insulin, and leptin/adiponectin/visfatin/resistin were determined. Patients and controls were comparable regarding body mass index (BMI), smoking, sedentariness, and menopause (p > 0.05). MetS (39.4 vs. 16.9 %, p = 0.005), hypertension (p = 0.004), and dyslipidemia (p = 0.002) were more frequent in patients than controls. IL-1beta, IL-6, BAFF, resistin, and adiponectin levels were higher in patients than controls (p < 0.05). pSS patients with MetS (n = 28) had higher BMI, waist circumference, cholesterol, LDL-C, triglycerides, insulin, leptin and HOMA-IR values, and greater hypertension and diabetes rates than pSS patients without MetS (n = 43) (p < 0.05). Current and/or previous prednisone use (75.0 vs. 62.8 %, p = 0.313), current (3.0 ± 4.5 vs. 1.6 ± 3.2 mg/day, p = 0.299), and cumulative prednisone doses (p = 0.495) were similar in both groups. Otherwise, IL-1beta level was higher in MetS patients than in non-MetS patients (p = 0.012), and this finding was confirmed (p = 0.048) by multivariate analysis with adjustments for age, ethnicity, prednisone use, current and cumulative prednisone doses, and duration of use. We identified high MetS frequency and abnormal adipocytokine profile in pSS. The association of MetS with elevated IL-1beta level suggests that inflammation plays an important role in its pathogenesis.

The clinical utility of anti-ribosomal P autoantibodies in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can affect multiple organs and thus has a large spectrum of clinical presentations. Assessment of the autoantibody profile is fundamental for the clinical management of SLE patients, providing important data for diagnosis, clinical characterization and disease activity evaluation. Anti-ribosomal P protein (anti-Rib-P, anti-P) antibody, described in the 1980s, is a serological marker for SLE that is present in 13-20% of cases. This reactivity was initially thought to be associated with neuropsychiatric involvement in SLE, with certain conflicting results. Subsequently, associations of anti-Rib-P with liver and renal involvement in lupus were reported. Recently, anti-Rib-P was detected in autoimmune hepatitis patients. Anti-Rib-P reactivity to Trypanosoma cruzi ribosomal target antigens in patients with Chagas heart disease has also been described. This review focuses on the usefulness of the determination of anti-Rib-P in SLE and in other autoimmune and non-autoimmune disorders in clinical practice.

Short and long-term effects of pandemic unadjuvanted influenza A(H1N1)pdm09 vaccine on clinical manifestations and autoantibody profile in primary Sjögren's syndrome.

Despite WHO recommendations about the A/California/7/2009/H1N1-like virus vaccination, studies evaluating its possible influence on clinical manifestations and autoantibody profile in primary Sjögren's syndrome (SS) are scarce. The aim of this study was to evaluate the possible influence of the unadjuvanted A/California/7/2009/H1N1-like virus vaccination on clinical manifestations and autoantibody profile in SS in the short/long-term. Thirty-six SS patients (The American-European Consensus Group Criteria, 2002) and 36 healthy controls with comparable mean age and gender were evaluated before and 21-days after this vaccination regarding seroprotection/seroconversion, factor increase in geometric mean titer (FI-GMT) and side effects. New onset of disease flares and autoantibody profile [antinuclear antibodies, anti-dsDNA, anti-Ro(SSA)/La(SSB), anti-RNP/anti-Sm, rheumatoid factor, anti-alpha-fodrin, anticardiolipin and anti-beta2-glycoprotein-I] were assessed before, 21-days and 1-year after vaccination. Patients and controls had similar rates of seroconversion (77.8 vs. 69.4%, p=0.42), seroprotection (83.3 vs. 72.2%, p=0.26) and FI-GMT (p=0.85). Disease duration, prednisone (2.1 ± 4.9 mg/day), methotrexate and azathioprine did not affect seroconversion (p>0.05). Regarding short-term, no change in the frequency or levels of autoantibodies was observed (p>0.05) and only mild side effects were reported in comparable rates to controls (p>0.05). During 1-year follow-up, the frequency of new disease flares was similar to the previous year (11 vs. 19%, p=0.51), and four patients developed positivity to one of the following specificities: anti-Ro(SSA)/anti-La/(SSB), anti-alpha-fodrin, or IgM anticardiolipin. None developed specific lupus autoantibodies. Of note, a significant increase in the mean levels of anti-Ro/SSA (p=0.0001) and anti-La/SSB (p=0.002) was detected after 1-year with no change in the other autoantibodies. This is the first study indicating that influenza A(H1N1)pdm09 vaccine induces long-term changes in autoantibody profile restricted to SS spectrum without a deleterious effect in disease course.

Testicular Sertoli cell function in ankylosing spondylitis.

To assess the testicular Sertoli cell function according to inhibin B levels in ankylosing spondylitis (AS) patients and the possible effect of anti-TNF therapy on this hormone production, 20 consecutive AS patients and 24 healthy controls were evaluated. At study entry, AS patients were not receiving sulfasalazine/methotrexate and never have used biological/cytotoxic agents. They were assessed by serum inhibin B levels, hormone profile, urological examination, testicular ultrasound, seminal parameters, and clinical features. Ten of these patients received anti-TNF treatment and they were reevaluated for Sertoli function and disease parameters at 6 months. Four of them agreed to repeat sperm analysis. At study entry, the median of inhibin B (68 vs. 112.9 pg/mL, p = 0.111), follicle-stimulating hormone levels (3.45 vs. 3.65 IU/L, p = 0.795), and the other hormones was comparable in AS patients and controls (p > 0.05). Sperm analysis was similar in AS patients and controls (p > 0.05) with one AS patient presenting borderline low inhibin B levels. Further analysis at 6 months of the 10 patients referred for anti-TNF therapy, including one with borderline inhibin B, revealed that median inhibin B levels remained stable (116.5 vs. 126.5 pg/mL, p = 0.431) with a significant improvement in C-reactive protein (27.8 vs. 2.27 mg/L, p = 0.039). Sperm motility and concentration were preserved in the four patients who repeated this analysis after TNF blockage. In conclusion, this was the first study to report, using a specific marker, a normal testicular Sertoli cell function in AS patients with mild to moderate disease activity.

Anti-lipoprotein lipase antibodies in patients with hypertriglyceridemia without associated autoimmune disease.

BACKGROUND: Anti-lipoprotein lipase antibodies have been described in rare cases of patients with hypertriglyceridemia. However, no systematic study evaluating these antibodies in patients with this lipid abnormality has been undertaken. OBJECTIVES: To analyze the correlation of anti-lipoprotein lipase (anti-LPL) antibodies with other laboratory findings in patients with hypertriglyceridemia but no autoimmune disease. METHODS: We evaluated 44 hypertriglyceridemic patients without autoimmune disease. Clinical and laboratory evaluations included analyses of comorbidities, fasting lipid profile and anti-LPL antibodies. RESULTS: Mean patient age was 55 +/- 10 years; 46% of the patients were female and 64% were Caucasian. The mean disease duration was 94.4 months and mean body mass index 28.7 +/- 3.6 kg/m2; 34.0% were diabetic, 25.0% were obese, 72.7% had systemic arterial hypertension, 75% were sedentary, 15.9% were smokers, 56.8% had a family history of dyslipidemia, 45.5% had a family history of coronary insufficiency, 20.5% had acute myocardial infarction, 9.0% had undergone revascularization and 11.0% angioplasty, 79.5% were being treated with statins and 43.2% were taking fibrates. Median triglyceride levels were 254 mg/dl (range 100-3781 mg/dl), and total cholesterol level was 233 t 111 mg/dl. High-density lipoprotein was 42.6 +/- 15.4 mg/dl, low-density lipoprotein 110.7 +/- 42.4 mg/dl and very low-density lipoprotein 48 +/- 15 mg/dl. Anti-LPL antibodies were identified in 2 patients (4.5%), both of whom had a family history of dyslipidemia, coronary insufficiency and acute myocardial infarction; one had undergone myocardial revascularization and percutaneous transluminal coronary angioplasty, and both were using fibrates and had normal triglyceride levels. CONCLUSIONS: Our findings demonstrate a correlation between the immune response and dyslipoproteinemia in hypertriglyceridemic patients, suggesting that autoimmune disease contributes to the dyslipidemia process.

Clues for previously undiagnosed connective tissue disease in patients with trigeminal neuralgia.

BACKGROUND: Connective tissue diseases (CTD) may be associated with idiopathic trigeminal neuralgia (TN). The prevalence and diagnostic implications of this association are, however, not well established. OBJECTIVES: The objective of this study was to evaluate, in TN patients, if rheumatologic clinical and laboratory findings could contribute to the early diagnosis of rheumatic diseases. METHODS: Forty-six consecutive TN patients, 67% female, mean disease duration 8.78 +/- 7.25 years, and 47 controls were initially interviewed using a standard questionnaire based on common signs/symptoms of systemic lupus erythematosus, Sjögren syndrome, mixed CTD, and systemic sclerosis. Autoantibodies were detected by standard techniques. Those with rheumatologic complaints or positive autoantibodies were referred to the Rheumatology Outpatient Clinic for a more detailed evaluation. Secondary causes of TN were excluded. RESULTS: The frequency of Raynaud phenomenon (P = 0.026) and ANA reactivity (P = 0.04) were significantly higher in TN patients compared with controls. Fourteen TN patients were ANA positive. Seven of them reported concomitant rheumatic complaints, and interestingly, diffuse CTD was diagnosed in 4 (57%) of these patients: 1 systemic lupus erythematosus; 2 Sjögren syndrome; and 1 undifferentiated disease with scleritis and positive parotid scintigraphy. In all cases, TN preceded by at least 10 months the rheumatologic signs/symptoms. Moreover, these 4 TN patients with CTD had a higher frequency of sicca symptoms (P = 0.001) and higher titers of ANA (>or=1:320) (P = 0.006) than the remaining 42 TN patients without CTD diagnoses. Sixteen patients had isolated laboratory or clinical abnormalities, and none of them had CTD diagnoses. CONCLUSIONS: The concomitant presence of sicca symptoms and high titer ANA are clues for the early investigation of rheumatic diseases in TN patients.

Ausência de anticorpos antilipoproteína lipase na doença de Behçet / Lack of anti-lipoprotein lipase in Behçet's disease

OBJETIVO: A recente descrição de anticorpos antilipoproteína lipase (anti-LPL) associados à dislipoproteinemia levounos a analisar sua presença e possível associação com achados clínicos e laboratoriais em pacientes com doença de Behçet. PACIENTES E MÉTODOS: Trinta e oito pacientes consecutivos com doença de Behçet [critérios do Grupo de Estudos Internacional em Doença de Behçet (International Study Group on Behçet's Disease - ISGBD)] foram testados para a presença de anticorpos anti-LPL através da técnica de ELISA. Foi realizada avaliação clínica e laboratorial, incluindo perfil lipídico de jejum, pesquisa de autoanticorpos e marcadores inflamatórios (PCR, VHS) na inclusão dos pacientes. Os critérios de exclusão foram quaisquer condição que afetassem o perfil lipídico. RESULTADOS: A média de idade foi de 42 ± 9 anos, sendo 68 por cento do sexo feminino e 68 por cento da cor branca. O tempo médio de duração da doença foi de 9,8 ± 7,5 anos. Vinte e nove por cento dos pacientes apresentaram história de trombose. Os níveis de PCR estavam elevados em 31 por cento dos pacientes e VHS aumentada foi detectada em 31 por cento, com níveis médios de 5,95 ± 10,3 mcg/mL e 14,5 ± 13,2 mm/1ªhora, respectivamente. Cerca de 47 por cento dos pacientes estavam tomando prednisona, com dose média de 7,6 ± 10,8 mg/dia. Quanto aos níveis de risco cardiovascular da NCEP/ATPIII, colesterol elevado foi verificado em 26 por cento, triglicerídeos em 18 por cento, HDL baixo em 15 por cento e elevado LDL em 25 por cento dos pacientes com Behçet. Os níveis médios de CT foram 198 ± 48 mg/dL, de triglicerídeos 121 ± 61 mg/dL, HDL 52.4 ± 14.7 mg/dL e LDL 119 ± 35 mg/dL. Anticorpos anti-LPL to subtipo IgG foram detectados em 0/30 pacientes com Behçet. CONCLUSÃO: Esses dados aqui apresentados corroboram uma ausência de ligação entre inflamação, resposta imunológica e dislipoproteinemia nos pacientes com doença de Behçet e sugerem que outros mecanismos estão associados ...

OBJECTIVE: The recent description of anti-lipoprotein lipase antibodies (anti-LPL) associated with dislipoproteinemia led us to analyze its presence and possible association with clinical and laboratorial findings in patients with Behçet's disease. PATIENTS AND METHODS: Thirty-eight consecutive patients with Behçet's disease [International Study Group for Behçet's Disease (ISGBD) criteria] were tested for the presence of anti-LPL antibodies by ELISA. Patients underwent clinical and laboratorial evaluation, including fasting lipid profile, determination of autoantibodies, and inflammatory markers (CRP, ESR) before inclusion in the study. Exclusion criteria were as follows: any conditions that affected the lipid profile. RESULTS: Patients had a mean age of 42 ± 9 years, 68 percent were females, and 68 percent were Caucasian. Mean disease duration was 9.8 ± 7.5 years. Twenty-nine percent of the patients had a history of thrombosis. C-reactive protein levels were elevated in 31 percent of the patients, and ESR was increased in 31 percent of the patients, with mean levels of 5.95 ± 10.3 mcg/mL and 14.5 ± 13.2 mm/1st hour, respectively. Approximately 47 percent of the patients were taking prednisone, with a mean dose of 7.6 ± 10.8 mg/day. As for NCEP/ATPIII cardiovascular risk levels, cholesterol levels were elevated in 26 percent of the patients, triglycerides in 18 percent, low HDL in 15 percent, and elevated LDL in 25 percent of the patients with Behçet's disease. Mean total cholesterol levels were 198 ± 48 mg/dL, triglycerides 121 ± 61 mg/dL, HDL 52.4 ± 14.7 mg/dL, and LDL 119 ± 35 mf/dL. IgG anti-LPL antibodies were detected in 0/30 patients with Behçet's disease. CONCLUSION: The data presented here indicates the lack of correlation among inflammation, immune response, and dislipoproteinemia in patients with Behçet's disease and suggests that other mechanisms are associated ...

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.

Estudo longitudinal do anticorpo antilipoproteína lipase e sua relação com atividade de doença nos indivíduos com lúpus eritematoso sistêmico sem anticorpos anti-dsDNA / 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 por cento 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...

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 percent 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...

Anti-lipoprotein lipase antibodies: a new player in the complex atherosclerotic process in systemic lupus erythematosus?

OBJECTIVE: The novel description of antibodies to lipoprotein lipase (anti-LPL) associated with dyslipoproteinemia prompted us to analyze the association of anti-LPL with clinical and serologic features in patients with systemic lupus erythematosus (SLE) and its link to markers of inflammation that are known to be involved in atherogenesis. METHODS: Enzyme-linked immunosorbent assay was used to test for the presence of anti-LPL antibodies in 66 consecutive patients with SLE. Clinical and laboratory evaluation, including a fasting lipid profile, autoantibody screening, an assessment for markers of inflammation (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]), and the SLE Disease Activity Index (SLEDAI) were performed at the time of inclusion in the study. Exclusion criteria were any conditions that affect the lipid profile. SLE patients were categorized into 2 groups according to detection of these anti-LPL antibodies, as follows: anti-LPL+ and anti-LPL-. RESULTS: Anti-LPL antibody IgG was detected in 25 SLE patients (37.8%). Triglyceride levels were significantly higher in the anti-LPL+ group (112.4 +/- 50.2 versus 89.9 +/- 54.5 mg/dl in the anti-LPL- group; P = 0.033), but no significant differences between the 2 groups were detected for total, high-density lipoprotein, and low-density lipoprotein cholesterol levels. A higher frequency of elevated CRP levels and ESRs was observed in the anti-LPL+ group compared with the anti-LPL- group (44% and 17.1%, respectively [P = 0.023] and 52% and 19.5%, respectively [P = 0.013]). Moreover, SLE patients with anti-LPL antibodies also had significantly higher levels of CRP (11.1 +/- 16.4 versus 2.4 +/- 2.6 mug/ml; P = 0.036) and higher ESRs (33.4 +/- 29.8 versus 16.5 +/- 11.8 mm/hour; P = 0.020). Anti-LPL titers had a significant positive correlation with the CRP level (r = 0.56, P < 0.001), the ESR (r = 0.55, P < 0.001), the SLEDAI score (r = 0.45, P < 0.001), anti-double-stranded DNA (anti-dsDNA; r = 0.52, P < 0.001), and anticardiolipin IgG antibodies (r = 0.25, P = 0.04), and a significant negative correlation was detected with total hemolytic complement activity (CH100) (r = -0.34, P = 0.005). Reinforcing these findings, multiple regression analysis also revealed a significant association of anti-LPL with the CRP level (P = 0.025) and anti-dsDNA (P < 0.001). Importantly, a comparison of positive and negative anti-dsDNA sera revealed similar mean CRP levels (P = 0.56) and ESRs (P = 0.102), contrasting with the SLEDAI score (P = 0.004) and CH100 (P = 0.008). CONCLUSION: These data support the link between inflammation, immune response, and dyslipoproteinemia in SLE, introducing anti-LPL as a possible new player that may ultimately help in understanding the complex events of atherogenesis in this disease.