Impairment In Rheumatoid Arthritis Patients Research Articles

Albumin from sera of rheumatoid arthritis patients share multiple biochemical, biophysical and immunological properties with in vitro generated glyco-nitro-oxidized-albumin

The purpose of the present study is to explore the effects of endogenous stressors on structure and function of rheumatoid arthritis (RA) patients’ albumin. In contrast to glycated-albumin or nitro-oxidized-albumin, high titre antibodies against glyco-nitro-oxidized-albumin were found in the sera of RA patients. Also, compared to the other two modified forms of albumin, glyco-nitro-oxidized-albumin showed highest percent inhibition. Albumin isolated from RA patients’ sera displayed hyperchromicity and quenching of tyrosine and tryptophan fluorescence. Fluorescence spectroscopy studies also revealed the presence of dityrosine and advanced glycation end products in RA patient’s albumin. RA patients’ albumin showed weaker binding with 1-anilinonaphthalene-8-sulfonic acid dye. Secondary structure alterations were demonstrated by circular dichroism and Fourier transform infrared spectroscopy. Biochemical investigations revealed substantial decline in the availability of free side chains of amino acid residues; increased carbonyls and decreased sulfhydryls in RA patients’ albumin. The functional impairment in RA patients’ albumin was revealed by their low binding with bilirubin and cobalt. Liquid chromatography mass spectrometry analysis revealed the presence of Nε-(carboxymethyl) lysine and 3-nitrotyrosine in RA patients’ albumin. The amyloidogenic aggregation of RA patients’ albumin was confirmed by Congo red absorption and thioflavin-T fluorescence assays. The morphology of the aggregates was visualized under scanning and transmission electron microscope. From the above findings, we inferred that endogenous stress in RA patients have modified albumin and produce structural/functional abnormalities. Also, the presence of anti-glyco-nitro-oxidized-albumin antibodies along with other clinical features may be used as biomarker for the diagnosis and assessment of treatment responses in RA patients. Communicated by Ramaswamy H. Sarma

Prevalence of Sexual Dysfunction in Mexican Women with Rheumatoid Arthritis.

We estimate the prevalence and identified the associated factors of sexual dysfunction in Mexican women with rheumatoid arthritis (RA). A cross-sectional survey was applied to 100 women with RA and compared with 100 healthy, sexually active, adult women. Assessments included an interview using the Female Sexual Function Index (FSFI). Assessment of factors related to sexual dysfunction included gynecologic characteristics, disease activity (DAS-28), and functioning questionnaire (HAQ-DI). Mann-Whitney U test and the Chi-square test were used to compare medians and proportions between the groups. A multivariate logistic regression was performed using sexual dysfunction according to impairments shown by the FSFI. A higher proportion of RA patients had sexual dysfunction compared with controls. Domains with higher impairment in RA patients were desire, arousal, lubrication, and orgasm. A decrease in sexual function correlated with age (r = −0.365 p < 0.001) and higher scores in HAQ-DI (r = −0.261 p = 0.009). Those patients with a higher disability had higher impairments in desire, arousal, lubrication, and satisfaction. In the multivariate analysis, menopause was associated with sexual dysfunction (OR: 10.02; 95% CI: 1.05–95.40, p = 0.04), whereas use of methotrexate was a protective factor (OR: 0.32; 95% CI: 0.11–0.92, p = 0.03). Sexual dysfunction is highly prevalent in Mexican women with RA. Clinicians should systematically evaluate the impairment in sexual function in women with RA.

The value of ultrasound and magnetic resonance imaging scoring systems in explaining handgrip strength and functional impairment in rheumatoid arthritis patients: a pilot study

PurposeThe goal of this study is to investigate the relationship between joint inflammation and damage of the wrists and hands, measured by semiquantitative ultrasound and magnetic resonance imaging scoring systems, with functional disability and handgrip strength (HGs).Materials and methodsConsecutive adult RA patients with active disease, as defined by a Disease Activity Score 28 joints C-reactive protein (DAS28-CRP) > 3.2, underwent a cross-sectional evaluation comprehensive of a clinimetric assessment, an HGs evaluation, an ultrasound assessment aimed at calculating the UltraSound-CLinical ARthritis Activity (US-CLARA), and a magnetic resonance imaging scored according to the modified Simplified Rheumatoid Arthritis Magnetic Resonance Imaging Score (mod SAMIS). The Spearman’s rho correlation coefficient was used to test the correlations.ResultsSixty-six patients with RA were investigated (age 55.6 ± 12.2 years). The mod SAMIS total score and the US-CLARA had a weak but significant correlation (rho = 0.377, p = 0.0018). Among the mod SAMIS sub-scores, there was a significant relationship between mod SAMIS bone edema (SAMIS-BME) and US-CLARA (rho = 0.799, p < 0.001) and mod SAMIS synovitis (SAMIS synovitis) and US-CLARA (rho = 0.539, p < 0.001). There were also significant negative relationships between the HGs score and the mod SAMIS total score and US-CLARA (rho = − 0.309, p = 0.011 and rho = − 0.775, p < 0.0001, respectively).ConclusionsBME and synovitis have an influence on the function of the upper extremities. The US-CLARA and the mod SAMIS total score are intriguing options for semiquantitative assessment of joint inflammation and damage in RA.

ASSOCIATION OF STAT4 RS7574865 POLYMORPHISM WITH THE RISK OF RHEUMATOID ARTHRITIS DEVELOPMENT AND ITS CLINICAL CHARACTESTICS

A cohort of 287 patients with rheumatoid arthritis (RA) showed that molecular variants (minor T allele and homozygous TT genotype) of the STAT4 rs7574865 polymorphic locus increase the risk of RA development and impact the clinical characteristics of pathological process. Specifically, these variants are associated with high disease activity (р = 0.0023) and III-IV roentgenologic stages of the disease, as well as with grade 2 functional impairment in RA patients in case of disease duration more than 5 years. The revealed association of molecular variants of the studied STAT4 rs7574865 locus with clinical RA characteristics indicates that STAT4 rs7574865 polymorphism is an effective marker of an increased risk of RA development in the population of the Republic of Belarus.

Preliminary study of the association of serum irisin levels with poor sleep quality in rheumatoid arthritis patients

Study objectivesSleep disorders are significant problems in patients with rheumatoid arthritis (RA) and are associated with poor quality of life. Irisin is myokine which may have anti-inflammatory and energy regulatory roles. This study assessed the association of serum irisin levels with the quality of sleep and disease activity in RA patients. MethodsIn sum, 58 RA patients and 30 matched healthy controls were included. Disease activity score in 28 joints (DAS28-ESR) and the patients’ global score were calculated. RA patients were grouped according to the Pittsburgh Sleep Quality Index score (PSQI) into good-sleepers (group 1) defined as a PQSI score≤5 and poor sleepers (group 2) with a PSQI > 5. Serum irisin levels were measured for both patients and controls by commercially available enzyme-linked immunosorbent assay kits. ResultsPoor sleep quality was found in 26 (45%) of the RA patients. Irisin levels were significantly lower in RA patients with poor sleep compared to those with good sleep and healthy controls (p < 0.001). Serum irisin levels correlated inversely with disease duration, morning stiffness duration, DAS28-ESR, global score, and total PSQI score (r = −0.722 to −0.263 & p values≤0.001–0.04) indicating a possible anti-inflammatory role of irisin in RA patients. The analysis employed Student's t-test, ANOVA, and Pearson correlation. ConclusionsIrisin levels were decreased in RA patients with poor sleep quality compared to RA patients with good sleep quality and healthy controls, indicating a possible association of decreased serum irisin with sleep impairment in RA patients.

Antibodies to paraoxonase 1 are associated with oxidant status and endothelial activation in rheumatoid arthritis.

Traditional and non-traditional cardiovascular (CV) risk factors underlie CV disease occurrence in rheumatoid arthritis (RA). Recently, a functional impairment of high-density lipoprotein (HDL) has been observed. Although the actual players are unknown, anti-HDLs were associated with altered lipid profile, decreased paraoxonase 1 (PON1) activity and CV disease in RA. Therefore, we aimed to evaluate whether the presence of antibodies against PON1 may be involved in this scenario. IgG anti-PON1 antibodies were quantified by ELISA in serum samples from 212 RA patients, 175 healthy controls (HC) and 54 subjects with traditional CV risk factors (CVR). A subgroup of 13 RA patients was prospectively followed upon tumour necrosis factor-α (TNFα) blockade. Serum PON1 activity, nitric oxide (NO) and total antioxidant capacity (TAC) were measured. Interferon-γ (IFNγ), interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1), vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule (sICAM) and TNFα serum levels were assessed by immunoassays. PON1 rs662 (Q > R) status was studied by reverse transcription (RT)-PCR. IgG anti-PON1 antibodies are increased in RA patients compared with HC (P<0.0001) and CVR subjects (P<0.001), even after correcting for total IgG levels. Although no associations with lipid profile were found, a positive correlation with Health Assessment Questionnaire (HAQ) was observed (r=0.215, P=0.004). Anti-PON1 antibodies were associated with PON1 activity, NO and TAC, a rs662-mediated gene-dosage effect being found. Similarly, anti-PON1 antibodies were associated with sICAM serum levels in univariate and multivariate models. Finally, these antibodies were not affected by TNFα blockade. Anti-PON1 antibodies can be responsible for PON1 impairment in RA patients, with a potential impact on biomarkers of oxidative status and endothelial activation. A gene-environment interaction of rs662 variants is supported.

Cardiac Impairment in Rheumatoid Arthritis and Influence of Anti-TNFα Treatment.

There is evidence that rheumatoid arthritis (RA) is associated with higher overall and cardiovascular (CV) morbidity and mortality as compared with general population. Increased prevalence of traditional risk factors and chronic inflammation, that has been recognized as independent CV risk factor, may play an important role in atherosclerosis and subsequently ischemic heart disease development. However, myocardial dysfunction as a result of chronic inflammation and secondarily myocardial fibrosis markedly participates on heart failure development. Proinflammatory cytokines, such as C-reactive protein, tumor necrosis factor alpha (TNFα), interleukins 1 and 6, that are markedly increased in RA, play a role in the acceleration of atherosclerosis as well as myocardial fibrosis development. Several studies documented that increased CV risk was associated with seropositivity, disease activity score, citrullination, and duration of RA. Early detection of heart dysfunction is based on echocardiographic detection of diastolic dysfunction resulting from myocardial inflammation and fibrosis. Some studies showed also higher prevalence of left ventricular systolic dysfunction and increased prevalence of cardiac arrhythmias as compared to non-RA population. There are still controversies on the impact of NT-proBNP in predicting cardiac impairment in RA patients. Some authors consider it to be a sensitive noninvasive predictor of subclinical CV disease in these patients and also a predictor of all-cause mortality independently on traditional CV risk factors. However, the correlation with parameters of cardiac function was confirmed only in a few studies. The impact of biological treatment on progression of atherosclerosis and heart failure is still controversial and seems to be not harmful in young patients with normal left ventricular function. The effect of biologics, especially anti-TNFα drugs, is probably related to the cardiac function before treatment. Larger prospective clinical, echocardiographic, and magnetic resonance studies are needed.

THU0181 Short-Lasting Flares and HAQ Impairment in Rheumatoid Arthritis Patients in Remission According to the New Acr/Eular Criteria

BackgroundThe new remission criteria suggested by the ACR/EULAR study group for trials [1] are applied in the clinical practice, although they are considered rather strict [2]. Notwithstanding this criteria, patients...

FRI0065 Clinical factors associated with the progression of functional impairment in rheumatoid arthritis patients who maintained the remission criteria defined by the new acr/eular criteria

BackgroundRemission is considered a therapeutic target in the management of patients with rheumatoid arthritis (RA). In 2010, new remission criteria were proposed by ACR/EULAR to achieve better patient outcomes. We...

SAT0050 Voice Impairment in Rheumatoid Arthritis Patients: A Disease Activity Marker Often Overlooked

BackgroundRheumatoid arthritis (RA) may lead to voice impairment through several anatomical and functional alterations.ObjectivesTo evaluate the prevalence of voice impairment in RA patients and to determine the correlation with disease...

Chronic Inflammation and Low-Dose Glucocorticoid Effects on Glucose Metabolism in Premenopausal Females With Rheumatoid Arthritis Free of Conventional Metabolic Risk Factors

Chronic systemic inflammation is associated with increased cardiovascular mortality in patients with rheumatoid arthritis (RA). The aim of our study was to investigate association of glucose metabolism and inflammatory markers in a group of patients with rheumatoid arthritis free of other metabolic risk factors. Twenty-two premenopausal RA females (11 patients on low-dose GC (<8.5 mg/day of prednisone or equivalent), 11 patients without glucocorticoid therapy) and 15 age- and BMI-matched healthy females underwent the oral glucose tolerance test. The insulin sensitivity indices according Matsuda (ISI(MAT)) and Cederholm (ISI(CED)) as well as HOMA2 %S were calculated. Cytokines, lipid profile, non-esterified fatty acids (NEFA) and plasminogen activator inhibitor-1 (PAI-1) were measured in baseline blood samples. Despite elevated interleukin IL-6 and TNF alpha, glucose, insulin and C-peptide responses to oral glucose load as well as ISI(MAT), ISI(CED), PAI-1 and NEFA were comparable in both RA groups and healthy controls. HOMA2 %S correlated with disease activity. In conclusions, low-dose glucocorticoid treatment does not lead to glucose metabolism impairment in RA patients without other metabolic risk factors. Increased cardiovascular mortality and morbidity is probably due to a direct effect of systemic inflammation on myocardium and/or blood vessels.

Assessment of hand trabecular bone texture with high resolution direct digital radiograph in rheumatoid arthritis: A case control study

ObjectivesRheumatoid arthritis is characterized by an early inflammatory related periarticular osteopenia. A new high resolution direct digital X-ray device has been recently developed to provide bone texture analysis which is designed to assess changes in trabecular bone architecture. For the first time, we have evaluated trabecular bone texture impairment in rheumatoid arthritis patients compared to healthy controls. MethodsIn this cross-sectional study, the reproducibility was assessed by three separate digital X-rays of the right hand, with repositioning in 14 late rheumatoid arthritis patients and 14 healthy subjects. Then, trabecular bone texture of the MCP2 and MCP3 from patients enrolled in a prospective cohort of 78 rheumatoid arthritis patients was compared with that of 50 healthy subjects, using three texture parameters: Hmean, co-occurrence and run-length. ResultsThe coefficients of variation of the high resolution direct digital X-ray measurements ranged from 0.5 to 1.8%. Only the Hmean parameter was significantly decreased in rheumatoid arthritis patients compared to healthy subjects at MCP2 (0.637±0.040 vs 0.654±0.032, P<0.05) and at MCP3 (0.646±0.044 vs 0.665±0.037, P<0.05). This reduction was significantly correlated to disease activity. ConclusionsThis study demonstrated both the good reproducibility of the high resolution digital X-ray measurements and the trabecular bone texture impairment at MCP joints in rheumatoid arthritis patients. In addition to provide a high resolution hand radiograph, this technique may represent an interesting tool to easily quantify periarticular osteopenia with a low radiation dose.

Therapeutic Strategies to Reverse Local Bone Loss in Erosive Arthritis

In rheumatoid arthritis (RA), the chronically inflamed joint undergoes profound phenotypical changes. Aside synovial inflammation and cartilage degeneration, subchondral bone erosions emerge early in the course of disease and are associated with functional impairment in RA patients. Chronic joint inflammation injures the bone as consequence of two key pathophysiological mechanisms: On the one hand, the proliferative synovial tissue (“pannus”) attracts monocytes/macrophages to migrate into the joint and provides specific signals for these cells to differentiate into bone-resorbing osteoclasts. These cells are activated by pro-inflammatory cytokines and resorb mineralized tissue. Second, the injured bone attempts to counteract bone resorption by attracting osteoblasts at the site of erosion. However, the inflammatory local environment prevents significant repair by overproduction of osteoblast-inhibitory mediators and facilitation of osteoblast apoptosis. Until now, osteoimmunology research in arthritis primarily focused on the mechanism of joint destruction and the effects of inhibiting osteoclasts. However, recent experimental studies imply that fostering bone formation in chronic erosive arthritis could potentially reverse joint destruction with induction of repair phenomena. This review discusses the pathomechanisms leading to impaired bone turnover and potential mediators that could be targeted to reverse bone loss in RA.

Assessment of foot impairment in rheumatoid arthritis patients by dynamic pedobarography

Objectives Impaired foot function may jeopardize the mobility of patients with rheumatoid arthritis (RA). However, there are still no guidelines concerning the adequate early treatment of painful rheumatoid feet which do not yet require surgery. An assessment method for RA feet appears necessary in order to detect foot problems before functional limitations develop. Therefore, the aim of the present study was to evaluate the use of pedobarographic measurements for detecting changes in plantar loading characteristics and their relationship to foot pain in patients with RA. Methods One hundred and twelve patients with RA (55.0 ± 11.0 years of age) were divided into three groups according to their Health Assessment Questionnaire (HAQ) Score and compared to a control group of 20 healthy adults (CG). Thirty-six patients with good physical capacity belonged to group 1 (RA1; HAQ-score: 0–1.0), 38 patients with moderate capacity to group 2 (RA2; score: 1.1–2.0) and 38 patients with low capacity to group 3 (RA3; score: 2.1–3.0). Each patient's foot pain was clinically assessed. Pedobarography was used to analyze foot loading parameters while walking barefoot. Results In the forefoot, average pressures under the lateral forefoot were higher in RA1 patients than in RA2 patients and controls ( p < 0.05) despite an inconspicuous clinical examination of the foot in RA1 patients. RA1 patients also demonstrated higher plantar pressures than RA2 under the second metatarsal head ( p < 0.05). In contrast, no significant differences in maximum force could be demonstrated between patient groups. Furthermore, in RA3 patients with lower physical capacity, foot pain was increased as compared to RA1 and RA2 patients. Conclusion In RA patients, pedobarographic patterns show specific changes which characterize the level of functional capacity. In patients with foot involvement, pedobarographic measurements can be useful during the earlier stages of the disease, when clinical examination does not yet indicate the need for more aggressive treatment or orthopedic interventions.

Cognitive impairment in rheumatoid arthritis.

The objective of this study was to determine the frequency of cognitive impairment in patients with rheumatoid arthritis (RA). A cross-sectional study of 40 patients with RA and 40 healthy controls was performed. To assess cognitive impairment, anxiety and depression, the following standardized psychiatric and clinical research methods were used: the Mini-Mental State Examination (MMSE), logic memory tests, short and long memory tests, verbal fluency tests, attention tests, the Brief Psychiatric Rating Scale (BPRS), the Hospital Anxiety and Depression (HAD)/CAGE scale and the Beck Depression Inventory (BDI). Patients and controls with incomplete primary education were excluded from the study. Statistics were performed by chi-square test and by Fisher's exact test. Cognitive impairment was observed in 30% of patients with RA and in 7.5% (p < 0.05) of healthy controls. Patients with RA had a significantly worse outcome in verbal fluency (p < 0.05), logic memory (p < 0.05) and short memory (p < 0.05). No statistical difference was observed among the results obtained in the MMSE, BPRS, HAD/CAGE and BDI. There was no significant relation to the duration of the illness, use of corticotherapy or disability. We observed a high prevalence of cognitive impairment in RA patients. Cognitive impairment was not related to clinical and treatment features or disability. More studies are necessary to determine clinical impact of cognitive impairment in RA.

Functioning in Rheumatoid Arthritis

Objective: There is increasing evidence and awareness that rheumatoid arthritis symptoms, such as joint pain and activity limitations, are strongly influenced by psychosocial variables. We hypothesized that depression is significantly associated with functional capabilities in rheumatoid arthritis (RA) patients. Method: We examined in a cross-sectional, retrospective data-based study the role of depression, pain severity, and self-efficacy in daily functioning in forty-five adult male veterans aged 55 and older who were patients with RA. Results: The overall RA disablement model of depression, pain severity, and self-efficacy accounted for 67% of predicted variance in disability. All independent variables were significantly associated with functional impairment in RA patients. Conclusions: Psychosocial factors, such as depression and self-efficacy, contribute greatly to disability in RA patients. Clinicians should carefully assess psychiatric and non-disease factors during medical evaluation in patients with RA.

Neuropsychological Rehabilitation

<h3>Background</h3> For long, rheumatoid arthritis (RA) was thought not to associate with central nervous system (CNS) involvement. In recent years some studies suggest that cognitive function is impaired in RA patients. Accelerated atherosclerosis and reduced function of intracranial vessels in RA can be associated with vascular dementia. <h3>Objectives</h3> We assessed RA patients and healthy controls by neuropsychological tests, cognitive function such as attention, intelligence, memory tests and also by anxiety and depression tests. We wished to explore the prevalence of neuropsychiatric manifestations and cognitive impairment in patients with RA. Intracerebral vascular lesions were investigated by brain MRI. <h3>Methods</h3> Sixty RA female patients were included. Among them, 20 were MTX-treated, biologic-free, 40 patients received biologics. The controls included 39 non-RA healthy women. The following standardised tests were used: the Montreal Cognitive Assesment (MoCa) Test, the Victoria Stroop Test (VST), the Spielberger State-Trait Anxiety Inventory (STAI), the Benton Visual Retention Test (BVRT), the Beck Depression Inventory (BDI), the Brigg’s and Nebe’s Test, the Trail Making Test (TMT) A and B, the Word fluency with the letter (WF-L) and with category naming tests (WF-C), the Rey-Osterreich Auditory Verbal Learning Test (RAVLT), the Weschler Adult Intelligence Scale (WAIS). We also performed brain MRI in all patients in order to associate cognitive function with MRI changes. <h3>Results</h3> The MoCa total score was significantly lower in RA patients (23.3±3.8) especially in biologic-treated group (22.6±4.3) compared to controls (25.6±2.4) (p=0,002; 0,001). The attention MoCa test score was significantly lower in biologic- (4.5±1.6) compared to MTX-treated patients (5.7±0.6)(p=0.001). The STAI scores were significantly higher in RA (STAIS: 45.5±8.5; STAIT: 48.0±11.0) compared to controls (STAIS: 36.9±9.1; STAIT: 41.1±9.0)(p&lt;0.001; 0.002). The BDI score was significantly higher in RA (13.2±8.8) and in biologic-treated patients (13.7±8.7) than in controls (8.9±6.5)(p&lt;0.05). The TMT scores were significantly higher in RA (TMT-A: 69.0±26.3; TMT-B:100.2±48.5) compared to controls (TMT-A: 53.1±14.3; TMT-B: 53.1±22.7)(p&lt;0,05). The VST scores were also significantly higher in RA vs controls. The WAIS and Benton scores were significantly lower in RA and in biologic-treated patients than in controls (p=0.005). On brain MRI scans, there were significantly more vascular lesions both in the left and the right side in RA patients (55,1%&gt;53,1%) than in controls (23,5%&gt;20,1%) (p&lt;0,05), the cerebral atrophy is much more common in RA (0,26 vs. 0,03;p=0,005). <h3>Conclusions</h3> These findings suggest that the presence of neuropsychiatric manifestations and cognitive impairment in RA patients is significant. Biologic-treated patients may represent a more severe RA subset thus having cognitive dysfunction more commonly. Brain atrophy, emollition and vascular lesions are more often in RA patients than controls. <h3>Disclosure of Interest</h3> None declared