Eloisa Bonfa

Association between Lupus Psychosis and Antiribosomal P Protein Antibodies

In 18 of 20 patients with psychosis secondary to systemic lupus erythematosus (SLE), autoantibodies to ribosomal P proteins were detected by immunoblotting and measured with a new radioimmunoassay using a synthetic peptide as antigen. The frequency of anti-P was not increased in patients with other central nervous system manifestations of SLE (3 of 20, by radioimmunoassay), in patients with transient behavioral abnormalities due to SLE (none of 8), in patients with psychosis who did not have SLE (none of 13), or in normal controls (none of 20). In four of five paired serum samples, anti-P-peptide antibody levels increased 5-fold to 30-fold during the active phase of lupus psychosis. Longitudinal studies of anti-P activity in two patients with psychosis revealed that anti-P levels increased before and during the active phases of psychosis but not during sepsis or other exacerbations of SLE, and that the elevations were selective for anti-P antibodies, as opposed to anti-DNA antibodies. Longitudinal studies of anti-P activity in two patients with anti-P but without psychosis showed less than threefold changes in anti-P levels despite exacerbations of disease. We conclude that anti-P is associated with lupus psychosis and that synthetic peptide antigens may be useful for the detection and measurement of autoantibodies to intracellular proteins.

Immunogenicity of Anti-TNF-α Agents in Autoimmune Diseases

Prognosis of several autoimmune diseases, especially rheumatoid arthritis (RA), ankylosing spondylitis, Crohn’s disease (CD), and psoriasis, usually refractory to conventional treatment improved considerably with the introduction of tumor necrosis factor alpha (TNF-α) antagonistic agents, which is now available (infliximab, etanercept, and adalimumab). However, a portion of patients persists with active disease, infusion reactions, and relapses even during current biological therapy. One of the reasons for this is the associated immunogenicity to these drugs. The incentive for induction of antibodies against anti-TNF-α agent depends mainly on its constitution. Chimerical drugs have a higher capacity of inducing immunogenicity compared to completely human drugs. Among the three anti-TNF-α agents, this phenomenon has been studied mainly in patients using infliximab, especially in RA and CD. The prevalence of anti-infliximab antibodies in RA varies from 12% to 44% and seems to be inversely proportional to the level of seric infliximab and therapeutic response. The use of etanercept was associated to the development of anti-etanercept antibodies in 0% to 18% of patients, without apparent effect on effectiveness or adverse events. Studies with RA and CD patients show prevalence of anti-adalimumab antibodies from 1% to 87%. Immunosuppressive drug addiction can reduce the induction of anti-TNF-α antibodies.

Chylomicron metabolism is markedly altered in systemic lupus erythematosus

OBJECTIVE To verify the in vivo status of chylomicron metabolism in systemic lupus erythematosus (SLE) since there is a high incidence of atherosclerosis in this disease and chylomicrons may have an important role in atherogenesis. METHODS A chylomicron-like emulsion labeled with 14C-cholesteryl esters and 3H-triglycerides was injected intravenously into 10 female patients with inactive SLE and 10 healthy age- and sex-matched control subjects to determine the plasma kinetics of the emulsion lipids from consecutive plasma samples taken at regular intervals for 1 hour. Lipolytic activity was determined in vitro after incubation of the labeled emulsion with postheparin plasma. RESULTS The decay curves for the emulsion were markedly slowed in SLE. Chylomicron lipolysis, indicated by the fractional clearance rate (FCR) of emulsion 3H-triglyceride, was 2-fold smaller in SLE patients than in controls (mean +/- SD 0.023 +/- 0.011 versus 0.047 +/-0.015 minute(-1); P = 0.010). Chylomicron removal, indicated by emulsion 14C-cholesteryl ester FCR, was 3-fold smaller in SLE patients than in controls (0.007 +/-0.007 versus 0.023 +/- 0.011 minute(-1); P = 0.009). In vitro lipolysis in SLE patients was nearly half that of the controls (mean +/- SD 10,199 +/- 2,959 versus 6,598 +/-2,215; P = 0.014). Higher levels of very-low-density lipoprotein cholesterol and triglycerides and lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I were also observed in the SLE patients. CONCLUSION SLE patients have disturbances in chylomicron metabolism that are characterized by decreased lipolysis and chylomicron remnant removal from the plasma. This finding, together with other alterations in lipid profiles that were confirmed in the present study, is largely accountable for the accelerated atherosclerotic process of the disease.

Antimalarial treatment may have a time‐dependent effect on lupus survival: Data from a multinational Latin American inception cohort

OBJECTIVE To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. METHODS Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). RESULTS Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6-98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6-11 months, 146 (12.8%) for 1-2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41-8.37), 2.7 (95% CI 1.41-4.76), and 0.54 (95% CI 0.37-0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18-4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39-0.99). CONCLUSION Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus.

Metabolic syndrome in rheumatological diseases.

Metabolic syndrome is characterized by a combination of various cardiovascular risk factors (age, gender, smoking, hypertension and dyslipidemia) that imply additional cardiovascular morbidity that is greater than the sum of the risks associated with each individual component. Herein, the authors review the rheumatological diseases in which metabolic syndrome has been studied: gout, osteoarthritis, systemic lupus erythematosus, rheumatoid arthritis, Sjögrens syndrome and ankylosing spondylitis. The prevalence of metabolic syndrome in these disorders varies from 14% to 62.8%. The great majority of these studies demonstrated that this frequency was higher in rheumatological diseases than in the control populations, suggesting that either the presence or the treatment of those diseases seems to influence the risk of developing metabolic syndrome.

Circulating follicular helper-like T cells in systemic lupus erythematosus: Association with disease activity

To assess circulating follicular helper T (Tfh)–like CD4+ T cells in patients with systemic lupus erythematosus (SLE) and determine their relationship to disease activity.

Safety and efficacy of hepatitis B vaccine in systemic lupus erythematosus

Hepatitis B virus (HBV) vaccination has been implicated as a potential trigger for autoimmune diseases but there are no prospective studies in lupus. We therefore assessed prospectively the safety and efficacy of immunization with recombinant DNA HBV vaccine (Euvax B®; LG Life Sciences) in systemic lupus erythematosus (SLE) patients. Twenty-eight consecutive inactive SLE patients [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) <4], age between 18 and 50 years and negative serology for HBV, were selected. Exclusion criteria were prednisone ≥20 mg/day and immunosuppressive drugs. Clinical and laboratorial assessments were obtained at study entry and one month after the three doses. In addition, a previous one year evaluation was performed using a standard electronic protocol. The mean age was 34 ± 7.7 years and disease duration was 10.4 ± 6.7 years. An adequate seroconversion was achieved at the end of the study (93%), although a lower frequency after the first (4%) and second dose (54%) was observed. No significant change in mean SLEDAI score was detected after each dose throughout the study (0.14 ± 0.52 versus 0 versus 0.61 ± 1.66 versus 0.36 ± 1.34, P = 0.11). Reinforcing these findings, the 11% flares during vaccination was similar to the 21% observed in the previous year (P = 0.46). Furthermore, the mean prednisone dose at study entry was comparable to the end of the study (2.86 ± 3.06 versus 4.64 ± 8.25 mg/day, P = 0.32). In addition, the frequency of immunosuppressive therapy during the vaccination period (11%) was alike to the 14% observed in the previous year before entry (P = 0.66). Hepatitis B vaccination was safe in inactive SLE patients with an adequate vaccine response rate. Lupus (2007) 16, 350—354.

Systemic lupus erythematosus and "lupus dyslipoproteinemia".

A growing body of evidences reinforces the close link between systemic lupus erythematosus (SLE) and atherosclerosis which is due to traditional and nontraditional risk factors for cardiovascular diseases. It is now recognized that SLE has a particular pattern of dyslipoproteinemia characterized by low HDL levels and increased triglycerides, which is aggravated by flares. Multiple mechanisms can induce an altered lipoprotein metabolism in SLE such as cytokines produced during systemic inflammation, autoantibodies and therapy.

Resistance Training with Vascular Occlusion in Inclusion Body Myositis: A Case Study

UNLABELLED Inclusion body myositis (IBM) is a rare idiopathic inflammatory myopathy that produces remarkable muscle weakness. Resistance training with vascular occlusion has been shown to improve muscle strength and cross-sectional area in other muscle wasting conditions. PURPOSE We evaluated the efficacy of a moderate-intensity resistance training program combined with vascular occlusion by examining functional capacity, muscle morphology, and changes in the expression of genes related to muscle protein synthesis and proteolysis in a patient with IBM. METHODS A 65-yr-old man with IBM resistant to all proposed treatments underwent resistance training with vascular occlusion for 12 wk. Leg press one-repetition maximum; thigh cross-sectional area; balance, mobility, and muscle function; quality of life; and blood markers of inflammation and muscle damage were assessed at baseline and after the 12-wk program. The messenger RNA (mRNA) expression levels of mechanogrowth factor, mammalian target of rapamycin, atrogin-1, and muscle RING finger-1 were also quantified. RESULTS After the 12-wk training program, the patients leg press one-repetition maximum, balance and mobility function, and thigh cross-sectional area increased 15.9%, 60%, and 4.7%, respectively. All Short Form-36 Health Survey Questionnaire subscales demonstrated improvements as well, varying from 18% to 600%. mRNA expression of mechanogrowth factor increased 3.97-fold, whereas that of atrogin-1 decreased 0.62-fold. Muscle RING finger-1 and mammalian target of rapamycin mRNA levels were only slightly altered, 1.18- and 1.28-fold, respectively. Importantly, the exercise did not induce disease flare. CONCLUSIONS We describe a novel, and likely the first, nonpharmacological therapeutic tool that might be able to counteract the muscle atrophy and the declining strength that usually occur in IBM.

Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases

Background Despite the WHO recommendation that the 2010–2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. Methods 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behçets disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjögrens syndrome, Takayasus arteritis, polymyositis and Granulomatosis with polyangiitis (Wegeners) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. Results After immunisation, seroprotection rates (68.5% vs 82.9% p<0.0001), seroconversion rates (63.4% vs 76.9%, p<0.001) and the factor increase in GMT (8.9 vs 13.2 p<0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p<0.0001), RA (p<0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p<0.0001), RA (p<0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p<0.0001), RA (p<0.0001) and PsA (p<0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644)