405 Does antimalarial adherence decrease the risk of cardiovascular events and mortality among patients with incident systemic lupus erythematosus and rheumatoid arthritis? A population-based study

BackgroundAdherence to antimalarial regimens are suboptimal in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. Also, adherence is dynamic in nature, and varies over the time. Computing a single...

P001 Differential expression of key metabolic genes in antigen-specific B cell subsets in rheumatoid arthritis and systemic lupus erythematosus

Received October 16, 2004; revision received June 4, 2005; accepted June 7, 2005. Atherosclerosis is a multifactorial process that commences in childhood but manifests clinically later in life. Atherosclerosis is increasingly considered an immune system–mediated process of the vascular system. The presence of macrophages and activated lymphocytes within atherosclerotic plaques supports the concept of atherosclerosis as an immune system–mediated inflammatory disorder.1,2 Inflammation can aggravate atherosclerosis via different mechanisms secondary to autoimmunity, infectious diseases, and other proatherogenic changes that occur during the inflammatory state. Autoimmune rheumatic diseases (AIRDs) are associated with higher rates of cardiovascular morbidity and mortality, primarily secondary to accelerated atherosclerosis. This phenomenon can be attributed to traditional risk factors for atherosclerosis and use of specific drugs, such as corticosteroids, but also might be the result of other autoimmune and inflammatory mechanisms that are aggravated in AIRDs. Several AIRDs exhibit increased overt cardiovascular disease (CVD) prevalence as well as findings of advanced subclinical atherosclerosis, which may precede the appearance of a clinical disease and thus be a target of early identification and preventive therapy. Cells of the immune system can be found within atherosclerotic plaques, which suggests that they have a role in the atherogenic process. Their migration and activation within the plaques can be secondary to various stimuli, including infectious agents.3 These cells probably aggravate atherosclerosis, because CD4+ and CD8+ T-cell depletion reduced fatty streak formation in C57BL/6 mice. In addition, after crossing of apolipoprotein E (ApoE)-knockout mice with immunodeficient scid/scid mice, the offspring had a 73% reduction in aortic fatty streak lesions compared with the immunocompetent apoE mice. Moreover, when CD4+ T cells were transferred from the immunocompetent to the immunodeficient mice, they increased lesion area in the latter by 164%.4 It is therefore not surprising that as in autoimmune diseases, the cellular components …

Seroprevalence of SARS-CoV-2-specific antibodies and vaccination-related adverse events in systemic lupus erythematosus and rheumatoid arthritis

Objective To investigate the expression of miRNA-31 in peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients, and the relationship between miRNA-31 and disease activity of RA. Methods After obtaining the informed consent, peripheral blood samples of 56 RA patients, 12 systemic lupus erythematosus (SLE) patients, 6 Sjogren's syndrome (SS) patients and 30 healthy controls were collected from the Department of Rheumatology, Peking University Third Hospital. RNA was extracted from the PBMCs which were separated by Ficoll-Paque PLUS. The expression of miRNA-31 in the PBMCs of RA patients, SLE patients, SS patients and healthy controls was detected by real-time Polymerase Chain Reaction (PCR). Furthermore, according to the RA disease activity score (DAS28), RA patients were divided into high, moderate and low disease activity groups and remission group, and miRNA-31 expression was compared between different groups. Data were analyzed using t test or Mann-Whitney U test. Results The expression of miRNA-31 in PBMCs of RA patients was 7.25 times (P=0.003 8) higher when compared with that of the control group. To be specific, the expression of miRNA-31 was 10.63 times in PBMCs of high activity RA group (P=0.01) and 8.95 times in moderate activity RA group (P=0.000 3) when compared with that of the control group, and there was no significant difference between low activity, remission groups and control groups in terms of miRNA-31 expression. Furthermore, the expression of miRNA-31 in PBMCs of SLE patients was not significantly different from the control and miRNA-31 expression in PBMCs of SS patients was 1.64 times (P=0.02) higher than that of the RA patients, but the average level of miRNA-31 was much less than that of RA patients. The increased miRNA-31 may serve as a diagnostic marker for disease activity of RA. Key words: Arthritis, rheumatoid; Monocytes; MicoroRNAs

FRI0299 Mucosal-associated invariant t cell deficiency in systemic lupus erythematosus is realted to an intrinsic defect in the ca2+/calcineurin/nfat1 signallingpathway

To determine the role of antiphospholipid antibodies (aPL) and of Raynaud's phenomenon (RP) in the development of migraine in patients with systemic lupus erythematosus (SLE). 50 unselected SLE patients and 20 rheumatoid arthritis (RA) controls underwent an interview to define the presence of migraine according to the guidelines of the International Headache Society (1988). Serological tests for aPL were performed in all patients. SLE patients were divided according to positivity for RP and/or aPL into 4 subsets: R-/aPL-, R-/aPL+, R+/aPL- and R+/aPL+. Data were analysed using Fisher's exact test, Chi-square test and U Mann-Whitney test. SLE and RA patients were similar for demographic and clinical features; aPL positivity was found in a greater proportion of SLE patients versus RA controls (68% vs 25%, p=0.0036). 31 of the 50 lupic patients (62%) and 7 of the 20 RA controls (35%) suffered from migraine (OR=3, CI:1-8.9). Among SLE and RA patients, migraine was associated with aPL positivity (p=0.027 and p=0.019). Analysing the combined effect of aPL and RP on migraine, in R+/aPL+ patients we detected an higher frequency of migraine (85.7%) with respect to the patients negative for these two features (27%, p=0.0051, OR=16, CI:2.2-118) and to the patients positive only for aPL (65%, p=0.0031, OR=6.2, CI:1.2-32). Migraine in SLE and RA associates with aPL positivity. The simultaneous presence of RP increases by 2,5 times the probability of having migraine, suggesting that cerebral vasospasm might be more common in patients with peripheral vasospasm, given the presence of aPL.

Mixed connective tissue disease (MCTD) is a rare disorder characterized by symptoms that overlap two or more Autoimmune Connective Tissue Diseases (ACTDs). The aim of this study was to determine whether miRNAs participating in the TLRs signaling pathway could serve as biomarkers differentiating MCTD or other ACTD entities from a healthy control group and between groups of patients. Although the selected miRNA expression level was not significantly different between MCTD and control, we observed that miR-126 distinguishes MCTD patients from all other ACTD groups. The expression level of miRNAs was significantly higher in the serum of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients compared to controls. The miR-145 and -181a levels distinguished RA from other ACDT patients. miR-155 was specific for SLE patients. MiR-132, miR-143, and miR-29a distinguished RA and SLE patients from the systemic sclerosis (SSc) group. Additionally, some clinical parameters were significantly related to the miRNA expression profile in the SLE group. SLE and RA are characterized by a specific serum expression profile of the microRNAs associated with the Toll-like receptors (TLRs) signaling pathway. The analysis showed that their level distinguishes these groups from the control and from other ACTD patients. The present study did not reveal a good biomarker for MCTD patients.

Rhupus syndrome: Assessment of its prevalence and its clinical and instrumental characteristics in a prospective cohort of 103 SLE patients

Clinical significance of fibromyalgia syndrome in different rheumatic diseases: Relation to disease activity and quality of life

BackgroundVaccines are a crucial component of the global efforts to control the spread of COVID-19. Very little is known about COVID-19 vaccine responses in patients living with autoimmune rheumatic conditions in Africa. We examined the clinical reaction to COVID-19 vaccinations in Ghanaians diagnosed with autoimmune rheumatic disease.MethodsThis was a hospital-based interventional cohort study of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients recruited via regular face-to-face clinic visits. The systemic lupus erythematosus disease activity index Selena modification (SELENA-SLEDAI) and the disease activity score 28-joint count-erythrocyte sedimentation rate (DAS28-ESR) were used to measure changes in disease activity levels.ResultsThirty-eight (38) patients of which 21 (55.3%) were diagnosed with SLE and 17 (44.7%) with RA contributed data for analyses. Most (89.5%) of the patients were females, with a mean age of 37.4 years. The SLE patients experienced a notable increase in severe flares during weeks three and six, as well as the third and sixth months, followed by subsequent decreases in the twelfth month, while remission levels increased throughout the same period. Among RA patients, high disease activity decreased during weeks three and six, as well as the third, sixth, and twelfth months, with remission levels increasing during the same time. A low dose (≥ 50 < 75 mg) dose of azathioprine was at some point associated with having a severe flare among SLE patients. After both vaccine doses, SLE patients were the majority having experienced both local and systemic reactions, all resolving within 24 h. Approximately 73.7% of the patients were COVID-19 negative at baseline. During post-vaccination visits, this increased to 100% by week six, with no positives thereafter.ConclusionThis study explores COVID-19 vaccine responses in Ghanaian autoimmune rheumatic disease patients, revealing disease activity levels in RA patients improved after vaccination compared to SLE patients. Our findings identify a potential link between low-dose azathioprine and severe flares in SLE patients, particularly evident in the third-week post-vaccination. Further research is warranted to clarify these findings and guide tailored treatment approaches in this medically significant population during pandemics and vaccination efforts.

FOXO forkhead transcription factors play an important role in controlling lymphocyte activation and proliferation. To evaluate the possibility that FOXO transcriptional expression is dysregulated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients, we determined the quantities of FOXO1, FOXO3a, and FOXO4 transcripts in peripheral blood mononuclear cells (PBMCs) from normal controls as well as from SLE and RA patients. Results showed that FOXO1 and FOXO3a are dominant FOXO factors at the transcript level in PBMCs. Statistical analysis showed that the FOXO1 transcript levels in RA patients and in SLE patients with active disease activity were significantly lower than those in normal controls, and the FOXO1 transcript levels were inversely correlated with lupus disease activity. In contrast, the differences in FOXO3a and FOXO4 transcript levels between normal controls and patients were not significant. These data suggest that the transcriptional dysregulation in FOXO1 is possibly linked to the pathogenesis of SLE and RA.

Expressed in naturally occurring CD4+CD25+ regulatory T cells, FoxP3 plays an important role in maintaining immune tolerance. We therefore evaluated the possibility that the peripheral blood FOXP3+ T-cell deficiency is associated with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The FOXP3 expression in peripheral blood T cells were evaluated and correlated to the CD4 and CD25 expression by flow cytometric analysis. Cell frequencies of FOXP3+ T cells among CD4+ T cells and absolute FOXP3+ T cell counts in SLE and RA patients were determined for the statistical comparison with those in normal controls, and their correlation with disease activities in SLE patients was evaluated. The FOXP3 transcript levels in peripheral blood mononuclear cells (PBMCs) were also determined to correlate the FOXP3+ T-cell quantity and to evaluate the possible dysregulation in the expression of two FOXP3 mRNA variants in patients. SLE patients had the higher FOXP3+ T-cell frequency and absolute CD4+CD25-FOXP3+ cell count than normal individuals, and the frequencies of CD4+CD25+FOXP3+ and CD4+FOXP3+ cells were positively correlated with the disease activities in SLE patients. In contrast, the differences in frequencies and absolute counts of FOXP3+ T cells between normal controls and RA patients were found to be insignificant. Moreover, SLE and RA patients appear to express two FOXP3 transcript variants in peripheral blood mononuclear cells at the levels similar to normal individuals. The peripheral blood FOXP3+ T-cell frequency among CD4+ T cells is altered in SLE patients with the active disease activity. Therefore, the analysis on peripheral blood FOXP3+ T cells may be useful for the evaluation of lupus disease activity.

The aim of this study was to evaluate the association of polymorphism in IL-1 receptor antagonist (IL-1RA) gene intron 2 with susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and their clinical features. Polymerase chain reaction of a genomic DNA was used to determine genotypes of the IL-1RA in 138 RA, 93 SLE, and 127 healthy control subjects. The frequency of IL-1RA allele 2 (IL-1RN*2) was lower in RA patients (2.5%) than in control subjects (7.1%) (odds ratio 0.34, 95% confidence interval 0.13-0.88, P=0.02). There was a significant difference in genotype and allele distribution between RA patients and controls. However, it did not differ between SLE patients and controls. In SLE and RA patients, there was no significant difference in clinical and laboratory findings concerning IL-1RA polymorphisms. In conclusion, our data suggest that IL-1RA gene polymorphism is not responsible for specific clinical characteristics in RA and SLE but that IL-1RN*2 is relevant in the susceptibility to RA, suggesting a protective role of IL-1RN*2 in the pathogenesis of RA.

To assess the frequency and factors associated with metabolic syndrome in adult female patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). During January and June 2006, 192 consecutive adult female patients seen during their scheduled appointment at the out-patient rheumatology clinic and meeting the American College of Rheumatology classification criteria for RA and SLE were invited to participate in this study. Sociodemographic, menopausal status, personal history of coronary heart disease, and physical activity were evaluated. According to the National Cholesterol Education Program Adult Treatment III (NCEP/ATP III), metabolic syndrome was defined as >or=3 of the following criteria: increased waist circumference (>88 cm or 35 inches), hypertriglyceridemia (>or=150 mg/dL), low (<40 mg/dL) high-density lipoprotein, hypertension, and high fasting glucose (>or=110 mg/dL). : One hundred-seven RA and 85 SLE patients with a mean age of 43 +/- 13 years were included in this study. The frequency of obesity and abnormal waist circumference were similar in RA and SLE patients. Two percent were underweight, 35% had a normal weight, 37% were overweight, and 25% were obese. The frequency of metabolic syndrome in RA and SLE patients was 17%. Metabolic syndrome was significantly associated with greater age, less education, lower income, and smoking. In RA patients, metabolic syndrome was significantly associated with a shorter treatment period with methotrexate, with pain, and with health assessment questionnaire scores. By multivariate logistic regression, the only statistically significant predictor of metabolic syndrome was smoking. The frequency of metabolic syndrome in RA and SLE patients was similar and associated with smoking. In RA patients, metabolic syndrome was related with pain and functional status, suggesting disease activity. A better control of disease activity may reduce the presence of metabolic syndrome and the risk of cardiovascular disease.