Risk Of Rheumatoid Arthritis Research Articles

The association between dietary total antioxidant capacity with risk of rheumatoid arthritis in adults: A case-control study.

Rheumatoid arthritis (RA) is a chronic disease associated and oxidative stress. The critical role of a dietary antioxidant in increasing the antioxidant defense system is undeniable and makes the assessment of the potential link between dietary antioxidants and diseases informative. Given the limited available data on dietary antioxidants, this study aimed to evaluate the association between DTAC and the risk of RA. This case-control study was carried out on 100 patients with RA and 197 healthy individuals aged 19-69 years. Data on dietary intake were collected using a validated 168-items quantitative food frequency questionnaire. DTAC was calculated based on the ferric reducing ability of plasma (FRAP), the ability of dietary antioxidants to reduce ferric to ferrous ions, presented in mmol per 100g of foods (mmol/100g). To find the association between DTAC and risk of RA, binary logistic regression adjusted for potential confounders was used. The mean age of the study participants was 49.26 and 40.88 years in the case and control groups, respectively. Participants in the top tertile of DTAC were less likely to have RA in the crude model (OR, 0.34; 95% CI, 0.18-0.64; P-trend: 0.001). Such that, when multiple potential confounders were controlled, the association remained significant in the full adjustment model (OR, 0.28; 95% CI, 0.10-0.76; P-trend: 0.001). The finding indicates a significant inverse association between DTAC and the risk of RA, suggesting that promoting a naturally elevated antioxidant capacity might help prevent the development of RA. Further prospective studies are required to confirm these findings.

Lifetime female hormonal exposure and risk of rheumatoid arthritis in postmenopausal women: Results from the French E3N cohort.

To assess the relationships between lifetime female hormonal exposures and the risk of incident RA in postmenopausal women. E3N is an ongoing French prospective cohort of 98,995 women since 1990 aged 40-65 years at enrolment. Data on reproductive/hormonal factors and treatments were regularly recorded. Exposures were defined as follows:-reproductive span (in years)=duration from menarche to menopause;-total ovulatory years=reproductive span-(number of full-term pregnancies×0.75+number of miscarriages×0.25+total duration of breast feeding+total duration of oral contraception);-lifetime duration of hormonal exposure (in years)=reproductive span+total duration of menopausal hormonal therapy;-composite estrogen score (CES, range=0-6): 1 point for each item: early menarche, high parity, history of hysterectomy, use of oral contraception, use of menopausal hormonal therapy and late menopause. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident RA were estimated using Cox proportional hazards regression models with age as the time scale. Among the 78,391 postmenopausal cohort women, 637 validated incident RA cases occurred. Lifetime durations of hormonal exposures were not associated with incident RA in postmenopausal women. High (CES=4-6) versus low (CES=0-1) estrogen exposure was inversely associated with the risk of RA: HR 0.37; 95% CI 0.2-0.8. In the E3N cohort, high lifetime estrogen exposure, that summarizes cumulative endogenous and exogenous exposures, was associated with a decreased risk of RA in postmenopausal women.

Exploring preferences of at-risk individuals for preventive treatments for rheumatoid arthritis

Objective Some immunomodulatory drugs have been shown to delay the onset of, or lower the risk of developing, rheumatoid arthritis (RA), if given to individuals at risk. Several trials are ongoing in this area; however, little evidence is currently available about the views of those at risk of RA regarding preventive treatment. Method Three focus groups and three interviews explored factors that are relevant to first degree relatives (FDRs) of RA patients and members of the general public when considering taking preventive treatment for RA. The semi-structured qualitative interview prompts explored participant responses to hypothetical attributes of preventive RA medicines. Transcripts of focus group/interview proceedings were inductively coded and analysed using a framework approach. Results Twenty-one individuals (five FDRs, 16 members of the general public) took part in the study. Ten broad themes were identified describing factors that participants felt would influence their decisions about whether to take preventive treatment if they were at increased risk of RA. These related either directly to features of the specific treatment or to other factors, including personal characteristics, attitude towards taking medication, and an individual’s actual risk of developing RA. Conclusion This research highlights the importance of non-treatment factors in the decision-making process around preventive treatments, and will inform recruitment to clinical trials as well as information to support shared decision making by those considering preventive treatment. Studies of treatment preferences in individuals with a confirmed high risk of RA would further inform clinical trial design.

Association between beverage consumption and risk of rheumatoid arthritis: a prospective study from the French E3N Cohort.

To assess the relationship between consumption of largely consumed beverages (coffee, tea, alcohol and soft drinks) and the risk of RA. The E3N Study (Étude Épidémiologique auprès des femmes de la Mutuelle Générale de l'Éducation Nationale) is a French prospective cohort including 98 995 women since 1990. Food and beverage consumption was assessed using a validated food-frequency questionnaire. Hazard ratios (HR) and their 95% CI for incident RA were estimated by Cox proportional hazards model. Among 62 631 women, 481 incident RA cases were identified. Consumptions of tea, alcohol and sugar-sweetened soft drinks were not associated with RA risk. We observed a linear association between coffee consumption and RA risk [≥4 cups/day vs ≤1cup/day, HR = 1.24; 95% CI (0.94, 1.64), Ptrend = 0.04], and a higher risk of RA with artificially sweetened soft drinks consumption [consumers vs not, HR = 1.66; 95% CI (1.12, 2.45)], particularly in never-smokers. Among ever-smokers, moderate liquor intake was associated with a reduced risk of RA [1-3 glasses/week vs non-consumers, HR = 0.63; 95% CI (0.43, 0.91)] and moderate wine consumption with a reduced risk of seropositive RA. In a large cohort of women, tea, alcohol and sugar-sweetened soft drinks consumption was not associated with RA risk, whereas consumption of coffee (especially caffeinated coffee), and artificially sweetened soft drinks was associated with higher RA risk, particularly among never-smokers. If further confirmed, these results could lead to novel mechanistic hypotheses and to simple prevention measures.

Skin microcirculation dynamics are impaired in patients with rheumatoid arthritis and no cardiovascular comorbidities.

Rheumatoid arthritis (RA) is associated with increased cardiovascular disease (CVD) risk. Microvascular endothelial dysfunction contributes to the development of vascular injury and subsequent CVD. We hypothesised that RA patients exhibit blunted microvascular reactivity regardless of CVD risk factors and investigated potential associations with coronary microvascular perfusion and surrogate markers of CVD. This case-control study recruited RA patients and non-RA individuals in the absence of cardiovascular comorbidities. Skin microvascular reactivity was dynamically assessed using laser speckle contrast imaging coupled with post-occlusive reactive hyperaemia protocol. Applanation tonometry was applied to assess subendocardial viability ratio, an index of myocardial microvascular perfusion, and central arterial stiffness [carotid-femoral pulse wave velocity (PWV), augmentation index]. Peripheral arterial stiffness (carotid PWV, β-stiffness index) and carotid atherosclerosis (intima-media thickness) were assessed with carotid ultrasound software. Skin microvascular responses before and following reperfusion [baseline flux, occlusion flux, time-to-peak, peak magnitude, peak-to-baseline magnitude, baseline cutaneous vascular conductance (CVC), and percentage increase in CVC] were significantly impaired in RA patients (n=35) compared to controls (n=35). Presence of RA independently predicted altered microvascular reactivity in multivariate analysis. Skin microcirculation dynamics significantly correlated with coronary microvascular perfusion and peripheral arterial stiffness, yet not carotid atherosclerosis, even after adjustment for CVD risk factors. Patients with RA present impaired microvascular reactivity regardless of CVD risk factors at a preclinical stage preceding CVD. Assessment of skin microvascular dysfunction may reflect a state of generalised vasculopathy, including myocardial microvascular abnormalities, and serve as a non-invasive surrogate indicator of CVD risk in RA.

Exploratory analysis of the association between pyrethroid exposure and rheumatoid arthritis among US adults: 2007-2014 data analysis from the National Health and Nutrition Examination Survey (NHANES).

Previous studies indicate that pesticide use may play an important role in the occurrence and development of rheumatoid arthritis (RA); however, little is known about the effect of specific pesticides on RA. The objective of this study was to evaluate whether pyrethroid exposure was linked to RA in adults. Data were originated from the 2007-2014 National Health and Nutrition Examination Survey (NHANES). The levels of pyrethroid exposure were assessed by 3-phenoxybenzoic acid (3-PBA) concentrations in urine samples. We built multivariate logistic regression models to assess associations between pyrethroid exposure and RA among US adults. A restricted cubic spline plot (three knots) was applied to test whether there was a nonlinear relationship between exposure to pyrethroid pesticides and the prevalence of RA. Finally, 4384 subjects were included in our analysis with 278 RA patients. In crude model, higher level of 3-PBA (creatinine-adjusted) was positively associated with RA (OR: 1.51, 95% CI: 1.07, 2.15). After adjustment for sex, race/ethnicity, education, body mass index, family poverty income, level of education, marital status, smoking status, alcohol usage, physical activity, hypertension, and urinary creatinine, the highest (vs lowest) quartile of 3-PBA was associated with an increased prevalence of RA (OR: 1.23, 95% CI: 0.86, 1.79). Significantly positive associations between 3-PBA concentration and RA were observed in the population aged between 40 and 59years and with lower level of education. The restricted cubic spline plot presented an increase in trend and indicated that pyrethroid exposure was linearly associated with occurrence of RA (p for nonlinearity = 0.728). In conclusion, our study indicated that pyrethroid pesticide exposure was associated with an increased risk of RA. Higher levels of pyrethroid exposure were linearly associated with increased prevalence of RA in adults. Certainly, our findings are in great need of further corroboration by prospective studies with strict design.

Association between work physical activity, dietary factors, and risk of rheumatoid arthritis

ObjectiveWe aimed to determine the association of physical activity and dietary factors on RA risk. MethodsThis case-control study within the Mayo Clinic Biobank matched incident RA cases (two codes plus disease-modifying anti-rheumatic drug, PPV 95%) to controls 1:3 on age, sex, and recruitment year/location. A baseline questionnaire assessed activity and dietary exposures. Logistic regression models calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI) of RA for each of 45 activity/dietary exposures. ResultsWe identified 212 incident RA cases and 636 controls (mean age 64, 70% female). Active work physical activity was associated with elevated risk of RA (aOR 3.00, 95% CI 1.58–5.69 vs. sedentary); leisure activity was not (aOR 0.96, 95% CI 0.64–1.42 sedentary vs. active). Three or more servings high-fat food and 5+ servings fruits/vegetables daily showed non-significant associations with RA (aOR 1.22, 95% CI 0.74–2.00 vs. 0–1 time; aOR 0.75, 95% CI 0.51–1.11 vs. 0–3 times), especially in sensitivity analyses with at least five years between questionnaire and RA (aOR 1.80, 95% CI 0.69–4.71; aOR 0.54, 95% CI 0.27–1.08). Alcohol binging was not associated with RA risk (aOR 1.28, 95% CI 0.56–2.96). Finally, sensitivity (versus primary) analyses showed a nonsignificant increase in RA risk for most vitamins and supplements. ConclusionActive work physical activity and some nutritional profiles (increased high-fat, reduced fruit/vegetable consumption) may be associated with increased risk of RA. Confirmatory studies are needed.

Pregnancy loss and the risk of rheumatoid arthritis in Chinese women: findings from the China Kadoorie biobank

Considering the female preponderance of rheumatoid arthritis (RA), and disease onset typically after the reproductive years, pregnancy and childbirth may play a role in the aetiology of the disease. Adverse outcomes of pregnancy have been found to precede the diagnosis of autoimmune diseases, including RA, but the evidence is scant and inconsistent. Therefore, we investigate whether pregnancy loss is associated with the risk of RA in Chinese women. Data from the China Kadoorie Biobank, conducted by the University of Oxford and the Chinese Centre for Disease Control and Prevention, of 299,629 Chinese women who had been pregnant were used. Multivariable logistic regression and stratified analyses were employed to analyse the association between types of pregnancy loss with the risk of RA. Pregnancy loss was significantly associated with increased risk of RA (OR 1.12, 95% CI 1.06–1.18), specifically, spontaneous (OR 1.11, 95% CI 1.03–1.20) and induced abortions (OR 1.11, 95% CI 1.06–1.17). There was no significant association between stillbirth and the risk of RA (OR 1.07, 95% CI 0.97–1.18). The risk of developing RA increases with the number of pregnancy losses: one loss confers an OR of 1.09 (95% CI 1.03–1.16), two an OR of 1.13 (95% CI 1.05–1.20), three or more an OR of 1.19 (95% CI 1.10–1.28) and OR of 1.06 (95% CI 1.03–1.08) for each additional. Spontaneous and induced abortions are associated with an increased risk of RA in Chinese women.

Preferences and Insights for Participation in a Rheumatoid Arthritis Clinical Prevention Trial: A Mixed-Methods Study.

In rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPA) can be elevated prior to inflammatory arthritis (IA). The potential to intervene in people with ACPA positivity underpins the development of prevention trials in RA. The Research Participation Influences Study examined factors influencing the decisions of individuals who are ACPA(+) to participate in a prevention trial using qualitative and quantitative methods. Individuals with ACPA positivity without IA were provided information regarding their risk for future RA, were provided a description of a clinical prevention trial using hydroxychloroquine, and were asked if they would participate in the trial. After agreeing to or declining participation, they were surveyed on what influenced their decision using Likert scales and open-response questions. Thirty-nine individuals who agreed to trial participation (enrollees) and 31 individuals who declined (nonenrollees) completed surveys. Enrollees expressed greater perceived risk for RA and greater perception of benefit to themselves or others than nonenrollees. Nonenrollees expressed greater concern about medication effects and less personal or family experience with RA than enrollees. There was a higher proportion of first-degree relatives (FDRs) of people with RA in enrollees versus nonenrollees (54% vs. 23%, P = 0.01). Enrollees were more likely than nonenrollees to be FDRs, exhibit stronger concern for personal risk for RA, and have less concern about adverse effects. Further exploration is needed to determine why these differences were present, including exploration of symptoms and the role of family history. Understanding these issues will better inform researchers and individuals who are candidates for prevention.

Risk of Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in Patients With Celiac Disease: A Population-Based Cohort Study.

Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort. We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged <18 and of RA in individuals with CD aged ≥18. We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged <18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82-3.95) over a follow-up of 7.0 years. Among individuals aged ≥ 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36-2.12) over a follow-up of 8.8 years. Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA.

PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico.

Citrullination is catalyzed by the peptidyl arginine deiminase 4 (PAD4) enzyme, encoded by the PADI4 gene. Increased PAD4 activity promotes the onset and progression of rheumatoid arthritis (RA). This study aimed to evaluate the association of PADI4 haplotypes with RA risk, mRNA expression, and the PAD4 activity in patients with RA from Mexico. Methodology: 100 RA patients and 100 control subjects (CS) were included. Genotyping was performed by PCR-RFLP method, PADI4 mRNA expression was quantified by real-time PCR, the contribution of PADI4 alleles (PADI4_89 G>A, PADI4_90 T>C, and PADI4_92 G>C) to mRNA expression by the ASTQ method, and PAD4 activity by HPLC. Also, the anti-CCP and anti-PADI4 antibodies were quantified by ELISA. Results: The three PADI4 polymorphisms were associated with RA susceptibility (OR = 1.72, p = 0.005; OR = 1.62; p = 0.014; OR = 1.69; p = 0.009; respectively). The 89G, 90T, and 92G alleles have a higher relative contribution to PADI4 mRNA expression from RA patients than 89A, 90C, and 92C alleles in RA patients. Moreover, the GTG/GTG haplotype was associated with RA susceptibility (OR = 2.86; p = 0.024). The GTG haplotype was associated with higher PADI4 mRNA expression (p = 0.04) and higher PAD4 enzymatic activity (p = 0.007) in RA patients. Conclusions: The evaluated polymorphisms contribute to PADI4 mRNA expression and the enzymatic activity of PAD4 in leukocytes. Therefore, the GTG haplotype is a genetic risk factor for RA in western Mexico, and is associated with increased PADI4 mRNA expression and higher PAD4 activity in these patients.

Self-reported and genetically predicted effects of coffee intake on rheumatoid arthritis: Epidemiological studies and Mendelian randomization analysis.

Background and aimsCausal research concerning coffee intake and rheumatoid arthritis (RA) risk is controversial. The objective of this study was to further explore the causal relationship between coffee intake and RA risk.MethodsThe 4,310 participants from NHANES 2003–2006 were included in an epidemiological study to assess the association between coffee intake and RA by weighted multivariate logistic regression. The inverse variance weighted (IVW) method of two-sample Mendelian randomization (MR), employing genetic data from UK Biobank (428,860 cases) of coffee intake and MR-Base platform (14,361 cases and 43,923 controls) of RA, was performed to estimate the causal relationship between coffee intake and RA.ResultsWeighted multivariate logistic regression suggested no significant correlation between coffee intake and RA. Compared to the no-coffee group, the odds ratio for RA in the <1, 1–3, ≥4 cups/day group were 1.297, 1.378, and 1.125 (P = 0.204, 0.098, and 0.698, respectively). In the IVW of MR analysis, there was no causal relationship between coffee intake and RA (OR = 1.47, P = 0.218).ConclusionOur study did not support a causal association between coffee intake and RA risk. However, it is necessary to consider valid information on coffee intake, including brewing method, type of coffee, and quantity, in further analysis of coffee intake and RA.

Preferences for preventive treatments for rheumatoid arthritis: discrete choice survey in the UK, Germany and Romania.

To quantify preferences for preventive therapies for rheumatoid arthritis (RA) across three countries. A web-based survey including a discrete choice experiment was administered to adults recruited via survey panels in the UK, Germany and Romania. Participants were asked to assume they were experiencing arthralgia and had a 60% chance of developing RA in the next 2 years and completed 15 choices between no treatment and two hypothetical preventive treatments. Treatments were defined by six attributes (effectiveness, risks and frequency/route of administration) with varying levels. Participants also completed a choice task with fixed profiles reflecting subjective estimates of candidate preventive treatments. Latent class models (LCMs) were conducted and the relative importance of attributes, benefit-risk trade-offs and predicted treatment uptake was subsequently calculated. Completed surveys from 2959 participants were included in the analysis. Most participants preferred treatment over no treatment and valued treatment effectiveness to reduce risk more than other attributes. A five-class LCM best fitted the data. Country, perceived risk of RA, health literacy and numeracy predicted class membership probability. Overall, the maximum acceptable risk for a 40% reduction in the chance of getting RA (60% to 20%) was 21.7%, 19.1% and 2.2% for mild side effects, serious infection and serious side effects, respectively. Predicted uptake of profiles reflecting candidate prevention therapies differed across classes. Effective preventive pharmacological treatments for RA were acceptable to most participants. The relative importance of treatment attributes and likely uptake of fixed treatment profiles were predicted by participant characteristics.

Beef intake and risk of rheumatoid arthritis: Insights from a cross-sectional study and two-sample Mendelian randomization.

BackgroundBeef is common in daily diet, but its association with the risk of rheumatoid arthritis (RA) remains uncertain. The objective of this study is to explore the relationship between beef intake and the risk of RA.Materials and methodsWe investigated the association between beef intake and risk of RA by multivariate logistic regression, based on the National Health and Nutrition Examination Survey (NHANES) 1999–2016 involving 9,618 participants. The dose–response relationship between beef intake and RA was explored as well. Furthermore, we performed Mendelian randomization (MR) analysis to examine the causal effect of beef intake on RA. Genetic instruments for beef intake were selected from a genome-wide association study (GWAS) including 335,576 individuals from the UK Biobank study, and summary statistics relating to RA were obtained from a GWAS meta-analysis of 14,361 RA patients and 43,923 controls. The inverse-variance weighted (IVW) approach was used to estimate the causal association, and MR-Egger regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were applied to evaluate the pleiotropy and outliers.ResultsCompared with the lowest quintile (0 to ≤33.50 g/d), beef intake was found to be significantly associated with the risk of RA [odds ratio (OR): 1.94; 95% confidence interval (CI): 1.20–3.12] in the third quintile (50.26 to ≤76.50 g/d). Moreover, a reversed “U” dose–response relationship between beef and RA (Pnon–linearity = 0.023) was found. In the MR analysis, beef intake was associated with an increased risk of RA (OR: 3.05; 95% CI: 1.11–8.35; P = 0.030) by the IVW method. The results from MR-Egger regression and MR-PRESSO test showed that there were no pleiotropic variations and outliers.ConclusionThis study indicated that there is suggestive evidence to support the causal effect of beef intake on the risk of RA, while further studies are warranted to elucidate the exact association.

Serum cholesterol loading capacity on macrophages is linked to coronary atherosclerosis and cardiovascular event risk in rheumatoid arthritis

ObjectivesCholesterol loading capacity (CLC) describes the ability of serum to deliver cholesterol to cells. It is linked to foam cell formation, a pivotal step in atherosclerotic plaque development. We evaluate...

Novel insight into the aetiology of rheumatoid arthritis gained by a cross-tissue transcriptome-wide association study

BackgroundAlthough genome-wide association studies (GWASs) have identified more than 100 loci associated with rheumatoid arthritis (RA) susceptibility, the causal genes and biological mechanisms remain largely unknown.MethodsA cross-tissue transcriptome-wide association study...

Evaluation of some trace elements and antioxidants in sera of patients with rheumatoid arthritis: a case-control study.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that destroys joints. The concentrations of elements (Zn, Cu, Mg, Mn, Fe, Ni, Cr, K, Na, Ca, Pb, and Cd), as well as antioxidant glutathione GSH and lipid peroxidation marker malondialdehyde MDA, will be determined in this study. The study involves 120 female RA patients and 60 healthy females in the control group, all of whom are between the ages of 20 and 60. Patients having diabetes, hypertension, hyperthyroidism, or psoriasis, in addition to RA, were excluded. When RA patients were compared to healthy individuals, the levels of Cu, Ni, Na, Pb, and Cd were significantly higher (p < 0.01), whereas the levels of Zn, Mg, Mn, Cr, Ca, K, and Fe were significantly lower (p < 0.01). The Cu/Zn (2.21 and 1.16) and Na/k (38.67 and 34.87) ratios were also found to be significantly higher in RA patients compared to controls. Furthermore, the data indicated that GSH concentrations in RA patients were significantly lower (p < 0.01) than those in controls (655.90 and 1345.17mol/l, respectively). MDA levels in RA patients were significantly higher (p < 0.01) than those in controls (2.739 and 1.673mol/l, respectively). The data indicate that Cu/Zn and Na/k ratios can be of great value in the diagnosis and evaluation of RA patients. On this basis, we conclude that these elements can be relied upon to provide indications of RA risk and the measurement of oxidative stress can serve as a biomarker to monitor disease activity and severity in RA patients. Key Points • Trace elements may be of value and may have an expected significance in the early diagnosis, prognosis, and treatment evaluation of rheumatoid arthritis. • The distortion in the levels of trace elements may reflect their possible role in the pathogenesis of rheumatoid arthritis. • Oxidative stress can act as a biomarker to monitor disease activity and severity in patients with rheumatoid arthritis. • The trace elements can contribute to the manifestation of inflammatory diseases due to their role in the synthesis of some antioxidants or due to their effect on the immune system.

Human serum paraben levels and their associations with rheumatoid arthritis: a case-control study from Hangzhou, China.

Parabens are widely used in consumer products resulting in frequent exposure to humans. To date, little is known about the association between human paraben exposure and rheumatoid arthritis (RA). In this study, a case-control study (n = 290) was conducted in Hangzhou, China, aiming to quantify the concentrations of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), and butyl paraben (BuP) in serum samples and to determine their associations with RA risks. MeP (mean 4.7 ng/mL, range <0.05-20 ng/mL) was the predominant paraben in human serum, followed by PrP (1.9 ng/mL, <0.12-24 ng/mL), EtP (1.4 ng/mL, <0.09-10 ng/mL), and BuP (1.09 ng/mL, <0.10-10 ng/mL). With 1-unit increase of MeP concentrations in human serum, the levels of rheumatoid factors, anticyclic citrullinated peptide antibody, and immunoglobulin G will increase by 0.19 unit (95% confidence intervals [CI]: 0.12-0.46), 0.30 unit (95% CI: 0.26-0.58), and 0.24 unit (95% CI: 0.21-0.30) in the adjusted model, respectively. One-unit increase of MeP and PrP concentrations in human serum was associated with an increase of 0.15 (95% CI: 0.037-0.28) and 0.20 (95% CI: 0.10-0.32) in the C-reactive protein concentrations. In addition, an association between serum MeP levels and the incidence of RA (odds ratios (OR)crude = 1.33, CI: 1.11-1.62, p = 0.03; ORadjusted = 1.86, CI: 1.32-2.63, p = 0.02) was positive and significant. Based on the measurements of serum paraben concentrations, this work supports the evidence for the significant associations among paraben exposure, change of specific immune marker, and RA risks.

Autoimmune diseases and atherothrombotic risk

Clinical investigators have long observed that patients with rheumatoid arthritis, inflammatory bowel disease, lupus, and psoriasis have increased rates of incident cardiovascular disease, often a decade earlier than among healthy individuals in the general population. 1 Solomon DH Karlson EW Rimm EB et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003; 107: 1303-1307 Crossref PubMed Scopus (1033) Google Scholar , 2 England BR Thiele GM Anderson DR Mikuls TR Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications. BMJ. 2018; 361k1036 PubMed Google Scholar For example, psoriasis, a common T-helper cell type 1/17 immunological disorder, confers an increased risk of myocardial infarction over the life span with the greatest relative increase in risk among those with severe disease in their 30s and 40s. 3 Gelfand JM Neimann AL Shin DB Wang X Margolis DJ Troxel AB Risk of myocardial infarction in patients with psoriasis. JAMA. 2006; 296: 1735-1741 Crossref PubMed Scopus (1466) Google Scholar Yet, to date, most studies of chronic inflammatory disorders and cardiovascular risk have focused on one disease entity at a time and used sampling techniques of moderate sample size. Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UKThese findings warrant targeted cardiovascular prevention measures, in particular in younger patients with autoimmune diseases, and further research into pathophysiological mechanisms underlying these complications. Full-Text PDF

Peptidylarginine Deiminase 2 Gene Polymorphisms in Subjects with Periodontitis Predispose to Rheumatoid Arthritis.

Epidemiologic studies have shown associations between periodontitis and rheumatoid arthritis (RA), but a causal relationship has not been established. Citrullination of gingival proteins by human peptidylarginine deiminases (PADs) or PAD from Porphyromonas gingivalis has been proposed to generate autoantigens in anti-CCP-positive RA. This study investigated whether the association between periodontitis and RA is influenced by single nucleotide polymorphisms (SNPs) in the genes encoding PAD2 and PAD4 that catalyze aberrant citrullination in RA and often are overexpressed in inflamed gingival connective tissue in subjects with periodontitis. The study included 137 RA patients and 161 controls with self-reported periodontitis. Periodontitis onset preceded RA onset by 13 years on average and was not associated with any of the SNPs investigated. In subjects with periodontitis, carriage of the minor alleles of rs2057094 and rs2235912 in PADI2 significantly increased the risk of RA (odds ratios 1.42 [p = 0.03] and 1.48 [p = 0.02], respectively), and this effect was driven by the anti-CCP-negative RA patients. The minor alleles of these SNPs only increased risk of anti-CCP-positive RA in individuals with periodontitis and a history of smoking. These data suggest that individuals with periodontitis carrying the minor alleles of SNPs rs2057094, rs2076616 and rs2235912 in PADI2 may be at increased risk of RA.