Female Rheumatoid Arthritis Patients Research Articles

Correlation between sarcopenia and nailfold microcirculation, serum 25-hydroxycholecalciferol (vitamin D3) and IL-17 levels in female patients with rheumatoid arthritis.

To investigate the correlation between sarcopenia and nailfold microcirculation and serum 25-hydroxycholecalciferol [25 (OH) D3] (instead of 25-hydroxyvitamin D) and IL-17 levels in female rheumatoid arthritis (RA) patients. 130 female rheumatoid arthritis (RA) patients and 80 healthy controls were tested. Nailfold capillaroscopic scores (NFCS) were measured. Bioimpedance analysis (BIA) was used to measure skeletal muscle mass. Enzyme-linked immunosorbant assay (ELISA) was used to detect the levels of IL-17, IL-6 and TNF-α. Serum 25 (OH) D3 concentration was determined by photochemical immunoassay. The correlation was analyzed by Pearson's correlation, and the influencing factors were analyzed by binary logistic regression. (1) Compared with the control group, NFCS and serum IL-17 levels were higher in the RA group, while the serum 25 (OH) D3 and skeletal mass index (SMI) were lower. (2) Pearson correlation analysis found: SMI was positively correlated with 25 (OH) D3 (r=0.515, P<0.001), SMI was negatively correlated with IL-17 (r=-0.468, P<0.001), SMI was negatively correlated with NFS (r = -0.229, P=0.009); (3) Logistic regression analysis: serum 25 (OH) D3 was a protective factor for sarcopenia (OR=0.392, P=0.016); IL-17, C-reactive protein, and NFS were risk factors for sarcopenia (OR=1.516, P=0.049; OR=1.469, P=0.045; OR=3.497, P=0.002). Secondary sarcopenia in RA is common and is closely related to microcirculation abnormalities. Increased NFCS is a risk factor for sarcopenia. Decreased serum 25 (OH) D3 levels and increased IL-17 are also risk factors for sarcopenia, but the mechanisms involved in sarcopenia and microcirculation abnormalities need further investigation.

Prevalence of Sarcopenia and Whole-Body Composition in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint deformity and disability, as well as muscle involvement. Sarcopenia is characterized by a progressive age-related loss of muscle mass and strength. The aim of this study was to evaluate the prevalence of sarcopenia and possible contributing factors associated with sarcopenia in RA patients. Adult RA patients (n = 105) of both sexes and 100 subjects as control group (CG) matched by age, sex, and body mass index were included in this cross-sectional study. Whole-body composition was measured by dual-energy x-ray absorptiometry. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass [ASM] index by dual-energy x-ray absorptiometry). The association between sarcopenia and associated factors was evaluated using logistic regression analyses. Significantly lower percentage of lean mass and ASM were found in the whole RA group compared with controls. However, lower lean parameters (total lean mass, percentage of lean mass, and ASM) were observed only in female subjects. The ASM index was significantly lower in female subjects with RA (RA 31.0% vs CG 11.9%) without differences in male subjects. On the other hand, fat mass and most adipose indices were significantly higher in both female and male subjects with RA. Female RA patients had higher prevalence of sarcopenia and sarcopenic obesity. Through univariate logistic regression analysis, the time of corticosteroids use, cumulative corticosteroid dose, previous fragility fractures, total lean mass, and ASM were associated with sarcopenia. Higher prevalence of sarcopenia and sarcopenic obesity were found in female RA patients. Sarcopenia was found in younger female subjects with RA compared with healthy control subjects. Sarcopenia was associated with previous fragility fractures in female patients with RA.

Whole exome sequencing (WES) of methotrexate response/adverse event profile in rheumatoid arthritis patients

Aim of the workTo preliminary study polymorphisms in a set of genes of relevance to methotrexate (MTX) response based on the Drug Bank database in Egyptian rheumatoid arthritis (RA) patients. Patients and methodsThe study included 10 consecutive adult female RA patients categorized according their response and adverse events (AEs) to MTX; patients with good response, ACR50 after 4 weeks was considered. Variant Call Format files were annotated and filtered via Drug Bank (11/9/2017) database in MTX. Accordingly, the following set of genes most related for RA MTX response were considered: SLC16A1, SLC7A11, SLC22A7, TBXAS1, PTK2B, ABCC2, ABCC4, SNORD13G, SLCO3A1, ABCC1, SLC46A1, SARM1, ABCB1, SLC19A, ATIC and SLCO1C1. Human genome DNA was assessed using Ion Ampliseq Exome Panel. Single-nucleotide variants (SNVs) and short insertions/deletions were identified ResultsThe mean age of the patients was 39 ± 12.5 years and disease duration 9.8 ± 7.4 years. AEs were present in 4 (2 poor and 2 good responders). 6 patients showed a good response with no AEs. Of the 16 studied genes, 19 variants were revealed. 18 SNVs and one deletion were detected. The C allele of ABCB1 was dominant in 7 out of 8 good responders’ (87.5%). The G of ATIC was present in 20% with AEs and poor response. The T and G of SLCO1C1 were in 60% of good responders. ConclusionIn Egyptian RA patients, there is evidence of a possible influence of a set of gene variants on the disease pathogenesis while others were related to MTX AEs and response.

The ovarian reserve as measured by the anti-Müllerian hormone is not diminished in patients with rheumatoid arthritis compared to the healthy population

Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory arthritis, affecting 0.5-1% worldwide population and predominates in females. Altered fertility has been reported due to a decrease in ovarian reserve secondary to sustained inflammation. The anti-Müllerian Hormone (AMH) is currently the most reliable biomarker of ovarian reserve. However, few and contradictory studies have been reported to analyse the relationship between fertility in RA female patients and AMH. The aim of present study is to determine the AMH serum concentrations in a long-standing RA patient group and control group. We also sought to determine the correlation between AMH serum levels and disease activity measured by different parameters and the effect of biological DMARDs. Serum AMH levels were measured in 60 women with long-standing RA aged 20-50 y.o. and compared to 59 healthy women. AMH was assessed by an electrochemiluminescence immunoassay method (ECLIA, Roche Diagnostics) and a large data set of clinical and molecular data was annotated. Demographic parameters, RA disease activity measured by DAS28 score and inflammatory biomarkers such as ESR, CRP, lymphocyte CD4+, CD8+, NK cells, IL-10 and IL-6 were determined. A comprehensive gynaecological self-administered questionnaire was given. Serum AMH levels were age-correlated. Differences between groups were calculated using Student's t-test or Mann-Whitney U-test for continuous variables and Fisher's exact test for categorical variables. Multivariate analysis was conducted by the partial correlation coefficient. Linear regression analysis was performed to study the effect of different variables on proportional AMH change. p-values <0.005 were considered significant. The median age was similar in AR and control groups (37.4±6.23 vs. 37.3±6.27 p=0.937). Mean disease duration was 8.37±5.36 years. The number of previous treatments was <3 in 71.7% of patients and ≥3 in 28.3%. Disease activity measured by DAS28 was 2.89± 1.54. The age-adjusted mean serum concentration of AMH was 1.27 ng/ml [IQR 0.42; 2.24] in RA patients and 1.31 ng/ml [IQR 0.46; 3.09] in controls (p=0.608). Neither disease activity (p=0.862), nor current or previous bDMARDs treatments (p=0.871) were associated with AMH levels. However, a negative linear correlation was observed between AMH and IL-10 levels (p=0.033). Our study shows that ovarian reserve determined by AMH serum levels is not reduced in rheumatoid arthritis patients compared with healthy controls. In our series, AMH levels were not affected by disease activity, however, a significant correlation was observed between AMH and IL-10 levels. These results support the role of cytokines profile in the female reproductive system and will focus further investigations in this critical area, mainly once biological DMARDs have been recommended in RA pregnant patients.

Twelve Weeks of Strengthening Exercise for Patients with Rheumatoid Arthritis: A Prospective Intervention Study.

Rheumatoid arthritis (RA) patients may benefit from exercise for several reasons. However, whole-limb strengthening exercises for such patients remain poorly studied. We hypothesized that systemic strength training that includes the upper and lower extremities would improve strength per se and enhance the quality of life. Here, we investigated the effects of 12 weeks of upper- and lower-limb strengthening exercise on the strength and quality of life of RA patients using the International Classification of Functioning, Disability, and Health model. This was a prospective, interventional controlled trial. Forty female RA patients were recruited and assigned to two groups not based on willingness to exercise, with 20 patients in the exercise group and 20 in the control group. All patients in the exercise group received once-weekly training sessions of 60 min over 12 weeks. All participants were assessed before and after the 12-week intervention period. We measured the hand grip strength and isometric quadriceps contraction, the cross-sectional area of the rectus femoris (CSA-RF) (via ultrasonography), and performed the 30 s sit-to-stand test and the 6 min walk test (6MWT). We derived the Borg scale score after the 6MWT and assessed the extent of social participation and quality of life using a Korean version of the 36-Item Short Form Health Survey (SF-36). A total of 35 subjects completed the experiment (18 in the exercise group, 17 in the control group). After the 12-week intervention period, the lower-limb strength and the CSA-RF were significantly increased in the exercise group. The activity level did not change significantly in either group. The exercise group exhibited significant improvements in the SF-36 mental health domain scores. Thus, strengthening exercise is useful for patients with RA.

Comparison of Some Physiological Parameters in Female Rheumatoid Arthritis Patients in Pre- and Postmenopausal Stages

Rheumatoid arthritis is an autoimmune disorder that is highly prevalent, leading to gradual cartilage distraction, and therefore is important to diagnose in the early stage. This study aimed to estimate the level of rheumatoid factor (RF) and Anti-citrullinated protein (Anti-ccp) in the serum of female patients. We also investigated several female reproductive hormones in the patients and compared their levels in the premenopausal and postmenopausal phases. The study included 88 female subjects, 50 suffering from signs of rheumatoid arthritis who were attending AL-Yarmouk teaching hospital, Baghdad, Iraq, and 38 without clinical signs of RA as a control group. The ELISA technique was used to estimate all the studied parameters. The results showed a significant elevation in the levels of RF (103.6 ± 227.0 vs. 22.1 ± 111.0 U/ml) and Anti-ccp (158.0 ± 170.0 vs. 0.51 ± 1.69 U/ml) in patient’s serum as compared to the control. The percentage of overweight and obese patients was higher than that of those with normal weight. Also, the current results showed significant differences in the serum concentrations of the reproductive hormones between the premenopausal and postmenopausal phases in the patients group. The level of FSH in postmenopausal female patients was higher than that in premenopausal ones (33.5 ± 17.9 vs. 9.01 ± 9.31 U/ml). Also, the level of luteinizing hormone (LH) in the postmenopausal patients was higher than that in the premenopausal patients (26.4 ± 12.3 vs. 12.7 ± 10.2 U/ml). While the level of prolactin (PRL) in RA postmenopausal female patients was lower than that in the premenopausal patients (8.60 ± 7.07 vs. 14.8 ± 10.6 ng/ml). In addition, the level of Anti-mullerian hormone (AMH) in post-menopausal patients was lower than that in the pre-menopausal ones (0.034 ± 0.023 vs. 0.635 ± 0.683 ng/ml). Finally, the concentration of estradiol (E2) in the post-menopausal female patients was lower than that in the pre-menopausal ones (32.9 ± 18.6 vs. 76.5 ± 43.6 ng/ml).

Differentially expressed lncRNAs in peripheral blood mononuclear cells from middle-aged female patients with rheumatoid arthritis-associated interstitial lung disease.

Interstitial lung disease (ILD) is frequently associated with rheumatoid arthritis (RA) and has a large impact on the prognosis of RA, particularly among females, with an increased prevalence and severity compared with that of males. Here, we aimed to investigate the lncRNA profiles in peripheral blood mononuclear cells (PBMCs) from middle-aged female patients with RA-ILD to determine whether they could help diagnose RA-ILD. We collected PBMCs from middle-aged female healthy controls, and RA and RA-ILD patients, excluding those with known risk factors of RA-ILD, such as being elderly or male, smoking, and having a history of other diseases. Then, a microarray analysis was applied to profile the lncRNA and mRNA levels in 3 pairs of samples. qPCR was performed to evaluate the candidate lncRNAs from 20 participants of each group. The expression levels of NR_002819, NR_038935, and ENST00000603415 were significantly increased in the RA-ILD group, while the expression level of ENST00000560199 was significantly decreased. As risk factors for RA-ILD, the area under the curve (AUC) values of NR_002819, NR_038935, and ENST00000603415 were 0.858, 0.704 (medium diagnostic accuracy), and 0.976 (high diagnostic accuracy), respectively. As a protective factor for RA-ILD, the AUC of ENST00000560199 was 0.853(medium diagnostic accuracy). To the best of our knowledge, this is the first study of lncRNA profiles in RA-ILD. The expression levels of NR_002819 (MALAT1), NR_038935, ENST00000603415, and ENST00000560199 were significantly different in the RA-ILD group and could be potential biomarkers for the assessment and diagnosis of middle-aged female RA-ILD patients. Key Points • The expression profile of lncRNAs in PBMCs from RA-ILD patients was evaluated. • NR_002819, NR_038935, and ENST00000603415 increased in RA-ILD patients. •ENST00000560199 decreased in RA-ILD patients. • The 4 lncRNAs might be potential biomarkers for diagnosis of RA-ILD.

The association between serum levels of growth differentiation factor-15 and rheumatoid arthritis activity.

Macrophages play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Growth differentiation factor-15 (GDF-15) acts as an autocrine regulator of macrophage activation. The aim of this study was to assess serum level of GDF-15 as a potential biomarker for detecting RA activity. A total of 100 female RA patients and 55 age and weight matched healthy control females were enroled. The serum level of GDF-15 was measured using enzyme-linked immunosorbent assay. Serum levels of GDF-15 in RA patients with high, moderate, low and no disease activity were 989.0±161.9, 505.6±220.5, 349.2±155.9 and 349.0±144.0pg/mL, respectively. GDF-15 with a cut-off value higher than 705pg/mL was indicative of high RA activity with sensitivity of 96% and specificity of 92%. GDF-15 serum levels may be used as a biomarker to predict high RA disease activity.

Circadian Rhythms of Endothelial Nitric Oxide Synthase and Toll-like Receptors 2 Production in Females with Rheumatoid Arthritis Depending on NOS3 Gene Polymorphism.

Rheumatoid Arthritis (RA) is an autoimmune polygenic disease characterized by rapid disability progression and high prevalence. Progression of RA is closely associated with chronobiological changes in the production of some hormones and inflammatory mediators, influencing the disease course and therapy efficacy. The main pathogenetic mechanism of RA is angiogenesis, which is controlled by biological clock-genes. Further investigation of circadian rhythms of angiogenic mediators production in RA patients may be considered as important and relevant. The aim of this study was to establish daily variability of serum endothelial Nitric Oxide Synthase (NOS3) and toll-like receptors 2 (sTLR2) levels in female RA patients depending on the NOS3 gene polymorphism. We examined 173 RA patients (100% female) aged 43.7 ± 7.35 years and 34 age-matched healthy women without joint diseases and autoimmune diseases (control). RA was diagnosed by ACR/EULAR 2010 criteria. Blood serum NOS3 and sTLR2 levels were determined at 08:00 and 20:00 using Cloud-Clone Corp kits (USA). NOS3 T-786С (rs2070744) polymorphism was determined by Real-Time PCR (Bio-Rad iCycler IQ5) using SNP-express kits. The SPSS22 software package was used for statistical processing of the results. Females with RA demonstrated oppositely directed serum NOS3 and sTLR2 daily changes: NOS3 level in the morning (08:00) was lower than in the evening (+ 45.5 ± 30.7%), and sTLR2 level in the evening (at 20:00) was lower than in the morning (-21.6 ± 13.1%). RA patients had differences in NOS3 and sTLR2 production depending on NOS3 T786C genotype. CC subjects had NOS3 level at 08:00, 20:00 and day average levels lower (16-25%), and sTLR2 level higher (24-27%) than those of TT subjects. RA patients, carriers of CC genotype, had higher chances of NOS3 and sTLR2 aberrant production compared to TT and TC genotype carriers (OR = 2.99 and 4.79, respectively). RA patients demonstrated oppositely directed circadian changes of serum NOS3 and sTLR2. CC genotype carriers had lower NOS3 and higher sTLR2 production rates than TT and TC genotype carriers.

The improvement in aerobic capacity, disease activity, and function in patients with rheumatoid arthritis following cardiac rehabilitation program: A single-center, controlled study.

This study aims to evaluate the effect of cardiac rehabilitation (CR) on disease activity, functional status, fitness, and modified cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA) with a moderate disease activity. This single-center, controlled study included a total of 60 female RA patients (mean age 57.5 years; range, 50 to 64 years) with moderate disease activity according to the Disease Activity Score-28 (DAS28) between January 2014 and June 2015. The patients were divided into two equal groups as those receiving CR program (n=30) and those receiving home exercise program (HEP; n=30). The patients were evaluated at baseline, at Weeks 10 and 24 using exercise tolerance test (i.e., The Metabolic Equivalent of Task [MET] and maximal oxygen uptake [VO2 max]), Six-Minute Walk Test (6MWT), DAS28, Health Assessment Questionnaire (HAQ), modified Systematic Coronary Risk Evaluation (mSCORE), Short Form Health Survey-36 (SF-36), and Beck Depression Inventory (BDI). There was a significant improvement in the VO2 max (p<0.001), MET (p<0.001), DAS28 (p<0.001), HAQ (p<0.001), BDI (p=0.005), SF-36 physical function (p=0.039), pain (p<0.001) and vitality subscale scores (p=0.008), and 6MWT (p<0.001), after the initial and repetitive exercise programs in the CR group compared to the HEP group. At the end of Week 24, full compliance with HEP was higher in the patients with CR group, compared to the HEP group (p<0.001). There was no significant effect of supervised exercise program on the mSCORE, although systolic blood pressure (p=0.033) and resting heart rate (p=0.049) were significantly improved in the CR group versus HEP group. Based on our study results, supervised exercise program cannot reduce CVD risk as assessed by the mSCORE, although it improves physical fitness, disease activity, and functional outcomes which may reduce traditional CVD risk factors in patients with RA.

THU0144 DESCRIPTIVE ANALYSIS OF PREGNANCY, DELIVERY, AND LACTATION IN PATIENTS WITH RHEUMATOID ARTHRITIS FROM THE IORRA COHORT.

Background:Rheumatoid Arthritis (RA) is common in women with reproductive age. For this reason, RA treatment during pregnancy and lactation is very important. In recent years, the use of biologic disease-modifying antirheumatic drugs (bDMARDs) has become common in RA treatment (1), treatment during pregnancy and lactation has changed drastically (2,3).Objectives:To investigate the pregnancy, delivery and lactation status of RA patients and treatment during that period in daily practice.Methods:The IORRA cohort is a large, single institute-based, observational cohort of RA patients established at Institute of Rheumatology, Tokyo Women’s Medical University, in 2000. We identified female RA patients aged 20-49 years who answered ‘pregnant’ or ‘delivered’ in the IORRA survey in 2010-2016 and whose pregnancies were confirmed in the medical records. We examined the Disease Activity Score with 28 joint count (DAS28)-CRP, medication use situation, the outcome of pregnancy, and lactation in those patients.Results:A total of 101 patients and 143 pregnancies were confirmed, of which 136 outcomes of pregnancy could be confirmed in the medical records. Among 136 confirmed pregnancy cases, there were 106 births and 30 miscarriages. Among 106 births, 4 cases (3.8%) were birth defects that could be confirmed in the medical records. The average age at pregnancy was 34.2±3.7 years and 36.1±3.3 years in delivered and miscarried cases, respectively. Miscarried cases were significantly older pregnancies (p=0.01). Of the 106 births, 65 birth weeks were confirmed, with an average of 37.9±1.8 weeks. The number of preterm delivery was 11 cases (16.9%). The average birth weight of 59 babies whose birth weight could be confirmed was 2699±517 g. There were 21 cases (35.6%) of low birth weight infants. The proportion of patients in DAS28-CRP remission was 73.1% before pregnancy, 61.6% during pregnancy, and 68.0% 1 year after delivery. Drugs used before pregnancy were glucocorticoid (48.8%), non-steroidal anti-inflammatory drugs (14.2%), conventional synthetic DMARDs (24.8%), and bDMARDs (48.0%). Etanercept accounted for 90% of bDMARDs. Among taking bDMARDs patients, 73.8% were discontinued after the pregnancy, and 26.2% were continued during pregnancy. Among those patients who continued bDMARDs, lactating patients were 12/26 (46.2%) cases after delivery, 10/30 (33.3%) cases in six months after delivery, and 7/36 (19.4%) cases in 1 year after delivery, respectively.Conclusion:The actual situation of pregnancy, delivery, and lactation in RA patients was revealed. Especially, bDMARDs were used at relatively high rates in RA patients who wish to have a child.

Association of body composition with disease activity and disability in rheumatoid arthritis

Background/AimsTo explore the associations between body composition and pain, disease activity, and disability in rheumatoid arthritis (RA).MethodsThe study enrolled 335 patients with RA and underwent body composition measurement with an InBody analyzer. The associations of body mass index (BMI), body fat mass, and skeletal muscle mass with disease activity score in 28 joints (DAS28), an index derived to measure the subjective component of DAS28 (DAS28-P), a pain visual analogue scale (VAS), and disability measured with the health assessment questionnaire (HAQ) were explored. Obesity was defined as BMI ≥ 25 kg/m2.ResultsThe median (interquartile range) disease duration was 6 years (3.5 to 9) and the mean DAS28 score was 3.6 ± 1.1. The mean BMI was 23.6 ± 3.6 kg/m2 and 109 patients (32.5%) were obese. Compared with non-obese patients, obese patients had a higher C-reactive protein (1.68 mg/dL vs. < 0.1 mg/dL, p = 0.013), higher pain VAS score (40 vs. 35, p = 0.031), and higher DAS28-erythrocyte sedimentation rate score (3.75 ± 1.18 vs. 3.46 ± 1.11, p = 0.031). In multivariate regression analysis, the DAS28 score in females was positively associated with the current steroid dose, body fat mass, and HAQ score, while the HAQ score in females was associated with older age, DAS28, lower skeletal muscle mass, and higher body fat/skeletal muscle ratio. In the multivariate regression analysis, the DAS28-P score in females was positively associated with body fat/skeletal muscle ratio and HAQ.ConclusionsBody composition, such as the body fat mass and body fat/skeletal muscle ratio, is significantly associated with disease activity and disability in female RA patients.

Aggrecan Turnover in Women with Rheumatoid Arthritis Treated with TNF-α Inhibitors.

This study was performed to evaluate the effects of 15-month anti-tumor necrosis factor α (anti-TNF-α) therapy on the aggrecan turnover of female rheumatoid arthritis (RA) patients. Serum was obtained from healthy subjects and female RA patients treated with TNF-α inhibitors (TNFαI) in combination with methotrexate. We measured serum levels of aggrecan chondroitin sulfate 846 epitope (CS846), aggrecan fragments (AGC), disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and 5 (ADAMTS-5), as well as their natural inhibitor, known as tissue inhibitor of matrix metalloproteinase-3 (TIMP-3), using immunoassay methods. Serum levels of CS846, AGC, ADAMTS-4, ADAMTS-5 and TIMP-3 were higher in female patients with RA before the treatment in comparison to healthy subjects. Ratio of ADAMTS-5 to TIMP-3 was significantly higher in RA women than in controls, whereas ADAMTS-4/TIMP-3 ratio did not differ from that in controls. During the anti-TNF-α therapy, the serum levels of 846 epitope increased, whereas levels of AGC decreased in female RA patients. Furthermore, 15 months of treatment with TNFαI downregulated serum levels of both ADAMTS, without any effect on TIMP-3 levels. These changes were accompanied by significantly reduced ratios of ADAMTS to TIMP-3. According to our results, anti-TNF-α therapy has a beneficial impact on aggrecan remodeling during RA.

Circulating microRNAs expression as predictors of clinical response in rheumatoid arthritis patients treated with green tea

Rheumatoid arthritis (RA) greatly affects the quality of life, as it causes multiple joint lesions or even joint deformity that result in varying degrees of functional impairment and disability. This study evaluated the correlation between circulating serum miR-125ba and miR-146a expression and clinical response to green tea therapy in RA patients.In total, 100 female RA patients and 50 healthy female controls were enrolled in this study and patients with RA received green tea therapy (5 cups/day; 1230 mg total catechins) for 24 weeks. Real time-PCR analysis was performed to determine miR-146a and miR-125 b levels from isolated peripheral blood mononuclear cells (PBMCs) of controls, and RA patients at baseline, 12 weeks, and 24 weeks of green tea treatment. There was a significant increase in circulating miR-125 b and decrease in miR-146 expression, and these were positively correlated with disease activity measures and pain intensity after 24 weeks of green tea therapy.The potential role of miR-146a and miR-125b in the diagnosis of RA and clinical therapeutic response to green tea was predicted using the analysis of the respective area under the receiver operating characteristic curve (AUC-ROC). Thus the data showed AUC-cut off values (miR-146a; 0.94, miR-125 b; 0.75) were best evaluated for clinical diagnosis of patients with RA, and that AUC-cut off values of 0.72 for miR-146a; and 0.87 for miR-125 b; were the best cut off values respectively reported for the prediction of RA clinical response to green tea therapy. Compared to non-responders, the data showed that miR-146a and miR-125 provide a stronger tendency towards green tea therapy in RA responders at 24 weeks. Our results showed that, miR-146a and miR-125 b expression levels could significantly predict clinical response to green tea therapy for 24 weeks in 65 % of RA patients. Changes in miR-146a and miR-125b levels after green tea therapy may result from the joint protective, antioxidant, and anti-inflammatory action of green tea. Both miR-146a and miR-125b could be used as diagnostic, therapeutic, and predictive biomarkers in green treatment and may have potential application in related non-drug RA therapy.

Effects of Methotrexate Therapy on the Levels of Gonadotropic Hormones in Rheumatoid Arthritis Patients of Reproductive Age.

Background: Methotrexate (MTX), which is the anchor drug in rheumatoid arthritis (RA), targets actively proliferating cells including the oocytes and granulosa cells which may impair the ovarian reserve. The purpose of this study was to determine the effects of MTX therapy on gonadotropic hormones, i.e. follicular stimulating hormone (FSH) and luteinizing hormone (LH) in female RA patients of reproductive age.Materials and methods: This is a cross-sectional study conducted at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC), from January 2018 to July 2018. Women with RA aged between 15 and 49 years who were on MTX therapy for at least six months, were consecutively recruited. All subjects were interviewed to gather information on their menstrual history and menopausal symptoms. The medical records were reviewed to obtain further data on the disease characteristics and RA treatment. The RA disease activity was determined using the DAS 28 scoring system. All subjects were tested for their serum FSH and LH levels.Results: A total of 40 patients were included in this study. The median dose of MTX used by the subjects was 12.5 mg weekly. The mean cumulative MTX dose was 1664.92 ± 738.61 mg. More than half (53.1%) of the subjects reported menopausal symptoms especially hot flushes. We found that FSH levels had a significant positive correlation with cumulative MTX dose [(r = 0.86), p < 0.001] and the duration of MTX therapy [(r = 0.84), p < 0.001]. Besides, there was a significant relationship between disease activity based on DAS 28 and FSH levels (p < 0.01). Age, body mass index, disease duration, and weekly MTX dose showed no associations with the FSH levels. On multivariate analysis, DAS 28 was found to be the only parameter that remained significant [β = 1.74 (95% CI 1.17-2.31), p < 0.001]. The LH levels, on the other hand, were not associated with MTX therapy or disease activity.Conclusion: Higher levels of FSH, which is an indicator of diminished ovarian reserve, have a significant positive relationship with disease activity, cumulative dose, and duration of MTX therapy in RA.

Quantification of hand muscle volume and composition in patients with rheumatoid arthritis, psoriatic arthritis and psoriasis

BackgroundPsoriasis (Pso), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are inflammatory diseases. PsA and RA are characterized by bone and muscle loss. In RA, bone loss has been extensively characterized, but muscle loss has, to the best of our knowledge, not been quantified to date.MethodsA random forest based segmentation method was used to analyze hand muscle volume in T1 weighted MRI images of 330 patients suffering from Pso, PsA or RA. In addition, fat volume was quantified using MRI Dixon sequences in a small subset (n = 32).ResultsMales had a higher relative muscle volume than females (14% for Pso, 11% for PsA, n.s. for RA). Between 40 and 80 years male Pso patients lost 13%, male PsA patients 16%, male RA patients 23% and female PsA patients 30% of their relative muscle volume. After adjustment for age, relative muscle volume in males RA patients was 16% and in female RA patients 9% lower than in Pso patients. In male RA patients relative muscle volume was 13% lower in than in male PsA patients. There was no difference in females. A significant negative correlation (R2 = 0.18) between relative intramuscular fat content relative hand muscle volume was observed.ConclusionThese preliminary data showed that relative hand muscle volume significantly decreased with age in male and female patients with Pso, PsA and RA patients. Independent of age, relative hand muscle volume was significantly smaller in patients with RA compared to the patients with Pso and the difference was twice as large in males compared to females. Also in male but not in female RA patients relative hand muscle volume was significantly smaller than in PsA patients.

Assessment of cervical spine involvement in rheumatoid arthritis patients in the era of biologics: a real-life, cross-sectional MRI study

Cervical spine involvement may lead to severe complications in rheumatoid arthritis (RA). In the era of modern therapies, atlantoaxial subluxation (AAS) may be rare; however, it may still be detected in asymptomatic patients. The onset of myelopathy can occur at any time. Altogether 49 female RA patients were included. Among them, 15 were methotrexate treated, biologic free, while 34 patients received biologics. The patients had no cervical pain or any neurological symptoms. We assessed the first (C1) and second (C2) cervical vertebrae by 3 T magnetic resonance imaging (MRI). In addition to AAS, we also determined odontoid erosion or periodontal soft tissue thickening. We associated our MRI findings with clinical, laboratory parameters, and hand radiography. We detected anterior AAS and soft tissue thickening in one-quarter, while odontoid erosions in eight (16%) of RA patients. There were no significant differences among the therapeutic subgroups. No posterior or vertical AAS was seen. Anterior AAS was associated with higher degree of inflammation, soft tissue thickening was seen at younger age, while odontoid erosions were associated with van der Heijde–Sharp scores of the hand. None of the patients had any lesions requiring surgery. The presence of cervical involvement in RA patients with 10–11 years of disease duration is still an important and frequent phenomenon. Higher disease activity and erosive disease are associated with atlantoaxial involvement. 3 T MRI is a sensitive method to assess AAS, as well as soft tissue lesions and odontoid erosions.

Hand Grip Strength in Elderly Rheumatoid Arthritis Patients

Aim: Previous studies have shown that rheumatoid arthritis and aging are independent risk factors for decreased hand grip strength. However, little is known about how coexisting rheumatoid arthritis would affect the reduced hand grip strength in the elderly population. Therefore, the aims of this study were to compare the hand grip strength of elderly female rheumatoid arthritis patients with controls and to investigate the factors associated with hand grip strength in the patients with rheumatoid arthritis.Material and Methods: This cross-sectional study included 45 elderly women with rheumatoid arthritis and 43 age-matched controls. All subjects were provided with self-reported questionnaires measuring physical disability, anxiety and depression, sleep quality, cognitive impairment, and fatigue severity. Hand grip strength was measured with hand dynamometer. The disease activity was assessed by the Disease Activity Score.Results: There were no significant differences in values of age, body mass index, physical disability, anxiety and depression, sleep quality, cognitive impairment, fatigue severity, and grip strength between the groups. Disease period, physical disability, and disease activity were variables which showed statistically significant negative correlation with grip strength in rheumatoid arthritis patients. In further linear regression analysis, it is found that only long disease duration was associated with decreased grip strength.Conclusion: Rheumatoid arthritis does not seem to significantly affect aging-related muscle strength loss. Disease duration was found to be the only independent factor associated with hand grip strength in elderly rheumatoid arthritis patients.

Pregnancy outcome in a cohort of Egyptian women with rheumatoid arthritis

BackgroundFemale patients with rheumatoid arthritis (RA) can have successful pregnancies. However, those who experience a higher disease activity during pregnancy and require continued treatment have a potential risk of maternal and neonatal complications. Aim of the workTo assess pregnancy outcome (adverse maternal and neonatal outcomes) in an Egyptian cohort of female RA patients. Patients and methodsThiscross-sectional study involved 200 female RA patients and 100 healthy age-matched controls. All were subjected to detailed gynecological history including: number of pregnancies, miscarriage, mode of delivery, maternal complication (gestational diabetes and preeclampsia), fetal complication (prematurity, low birth weight ‘LBW’ and congenital anomalies) and medicationsused during pregnancy. The disease activity score (DAS28) was assessed pre-conception and in each trimester. ResultsPatients had significantly lower number of pregnancies (p = 0.002) and deliveries (p = 0.001) and higher incidence of miscarriages (p = 0.022) compared to controls. Delivery by Cesarean section (CS) was higher inpatients (p = 0.001) with an increased risk of preeclampsia (p = 0.042). Both the antenatal and natal DAS28 significantly correlatedwith abortions, deliveries by CS and LBW (p = 0.005, p = 0.004 and p < 0.001, respectively). Pre-conceptional methotrexate use significantly correlated with the number of abortions (p = 0.02). Corticosteroid use during pregnancy was related to LBW of newborns (p = 0.03). ConclusionPregnant RA patients have higher frequency of abortion, delivery by CS, preeclampsia and LBW of newborns; especially those having higher disease activity and/ortreated with potentially harmful medications. It is crucial to educate female RA patients about these risks and they should be considered as high-risk pregnancy and followed accordingly.

Correlation the Cytomegalovirus (CMV) IgM Antibodies and Viral DNA Presence with Rheumatoid Arthritis (RA) in Iraqi Patients

In the Iraqi population, a high incidence (82.7%) of rheumatoid arthritis (RA) has been reported among the suspected patient. Many investigators studied the microbial infectious present in Iraqi patients with RA; however, to the best of our knowledge, there is no previous study detected the CMV DNA and antibodies to RA disease. Hence, the current study aimed to investigate the presence of CMV DNA and antibodies in Iraqi RA patients. A total of 58 blood samples were collected from patients with clinical signs of rheumatoid arthritis, along with 32 samples of apparently healthy individuals as a control group. These samples were tested for rheumatoid factor (RF), CMV IgM antibodies and viral DNA during the acute and the chronic periods of the autoimmune disease. The results showed that 46.6% (27/58) and 13.8% (8/58) of rheumatoid arthritis patients had positive reactions for IgM-CMV and CMV DNA, respectively, as compared to healthy individual. The highest rate of the viral occurrence was recorded in the aged and female RA patients (24 and 21 cases, respectively). Moreover, the most significant increases in RA appearance and CMV reactivation cases were observed in patients with a mean age higher than 40 years old. This finding pointed out the prevalence of viral infections mostly in RA patients aged more than 40 years old, accompanied by increased RA cases. This study concludes that patients with positive CMV must be tested for rheumatoid factor, especially when the viral DNA is present. Moreover, we recommend measuring TNF-α and IFN-γ as the proinflammatory cytokines that play an important role to protect against viral infection and prevent their reactivation in all RA patients.