Male Rheumatoid Arthritis Research Articles

Disease Activity, Inflammation Markers, and Quality of Life Are Associated with Muscle Strength in Croatian Rheumatoid Arthritis Patients-A National-Based Study.

Background and Objectives: Rheumatoid arthritis (RA) patients experience sarcopenia and decreased muscle mass and handgrip strength, leading to decreased quality of life and disability. The prevalence of RA varies across regions. This study aimed to evaluate the factors associated with RA in Croatian regional centres and explore correlations between clinical parameters and muscle strength. Materials and Methods: Included in this study were 267 stable RA patients from four Croatian clinical centres. The patients' mean age was 60.4 ± 12.0 years, with 12.7% of them being male. For each study participant, information was gathered on their anthropometric characteristics, clinical and laboratory indicators, quality of life, disease activity, and sociodemographics. Results: The main results showed that in the female RA participants, the significant positive predictors are weight, height, exercise, VAS, and haemoglobin level. The negative predictors are the use of conventional synthetic disease-modifying anti-rheumatic drugs, the use of biological disease-modifying anti-rheumatic drugs, the number of tender joints, the number of swollen joints, the estimated sedimentation rate, the C-reactive protein, the disease activity score, the parameters of the EQ5D, and being prescribed with three or more medications. In the male RA participants, significant predictors of muscle strength are only weight, height, and anxiety/depression difficulties, according to the EQ5D. Conclusions: This study showed correlations between muscle strength and the parameters of disease activity, inflammation parameters, health-related quality of life, therapy, and exercise in the female RA participants in Croatia.

High Quantitative CRP And Low Albumin as Marker of Disease Activity in Patients with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by synovial tissue inflammation, leading to joint damage, pain, and systemic effects. Objective: To evaluate the utility of high quantitative C-reactive protein (CRP) and low serum albumin levels as markers of disease activity in RA patients. Methods: This cross-sectional study was conducted at the Department of Rheumatology, Khyber Teaching Hospital, Peshawar, from September 1, 2023, to February 29, 2024. Male and female RA patients aged 18 to 70 years were enrolled. Disease activity was assessed using the Disease Activity Score 28 (DAS 28). Serum CRP and albumin levels were measured and compared with DAS28 scores. Results: A total of 105 patients were included, with a majority being female (n=60, 57.1%). The mean age was 52.4 ± 9.8 years, with most participants aged between 40 and 50 years (n = 35, 33.3%). Elevated CRP levels were associated with increased disease activity, with an odds ratio of 1.82 (95% CI: 1.53 - 2.17, p < 0.001). Conversely, lower albumin levels were linked to higher disease activity, with an odds ratio of 3.47 (95% CI: 4.35 - 2.63, p < 0.001). Conclusion: Serum CRP and albumin levels serve as valuable indicators for assessing disease activity in RA patients, highlighting their potential role in clinical management.

Incidence Rate of Cardiovascular Events in Rheumatoid Arthritis: An Observational Cohort Study in Saudi Arabia.

Rheumatoid arthritis (RA) doubles the morbidity of cardiovascular disease (CVD) and leads to a 50% increase in mortality compared to the general population. This study aims to estimate the CVD incidence among RA patients in Saudi Arabia (SA), vital for assessing CVD burdens within this group. This retrospective study took place at two centers in the Eastern Province of SA, including all adult RA patients who visited the rheumatology clinic from 2016 to 2021 and were prescribed disease-modifying antirheumatic drugs (DMARDs). CVD incidence was determined by the diagnosis of ischemic heart disease (IHD), stroke/transient ischemic attack (TIA), venous thromboembolism (VTE), heart failure (HF), and arrhythmia post-RA diagnosis. Additional data collected included demographics, CVD risk factors, comorbidities, RA-related factors, and medication usage. The study comprised 651 patients, 80.5% of whom were females with an average age of 51. The overall CVD incidence was 11.2 per 1000 person-years, with males experiencing five times more incidents than females. The prevalence of CVD risk factors included 18.7% with hypertension, 7.8% with hyperlipidemia, 18.9% with diabetes, and 42.9% with obesity. Significant predictors of CVD were male gender and RA duration, with adjusted odds ratios (aOR) of 3.17 (95% CI 1.10 to 9.14, P=0.033) and 64.81 (95% CI 3.68 to 1140.6, P=0.004), respectively. This unique study from SA examined the CVD incidence in RA patients, identifying long disease duration and male gender as significant predictors. Effective reduction of CVD risk in RA patients requires aggressive management of modifiable risk factors and regular risk assessments.

Whole-hand and regional bone mineral density involvement in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetric polyarthritis that can lead to joint deformity, disability, and osteoporosis. We aimed to evaluate whole hand and regional BMD in RA patients compared to controls. In addition, we evaluated the BMD of dominant versus non-dominant hands in healthy subjects. We included adult female and male RA patients and control subjects matched by age, sex, and BMI. BMD (g/cm2) was measured by DXA in lumbar spine (LS), whole hand, and three regions of interest: carpus, metacarpal bones, and phalanges. Results: 44 control subjects (49.5±11.8 y) and 60 with RA (52.7±12.7 y) were included. Significant lower BMD in RA patients was found in LS (−8.7%), dominant whole hand (−9.5%), carpus, metacarpal bones, and phalanges, and non-dominant whole hand (−8.7%), metacarpal bones, and phalanges compared to controls. A significant positive correlation was found between LS and whole-hand BMD (dominant r=.63, non-dominant r=.67). Finally, the whole hand, metacarpal bones, and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalangeal ROI. In conclusion, hand BMD was significantly lower in RA patients compared to control subjects and there was a significant correlation with LS BMD. We demonstrated that BMD measurements of the whole-hand, and different ROI (carpus, metacarpal bones, and phalanges) by DXA would be an easily reproducible technique to evaluate bone loss. In addition, the whole hand, metacarpal bones and carpus BMD measurements were significantly higher in the dominant hand compared to the non-dominant hand without differences in the phalanges.

Polybrominated biphenyls (PBBs) and prevalence of autoimmune disorders among members of the Michigan PBB registry

BackgroundPolybrominated biphenyls (PBBs), a class of endocrine disrupting chemicals, were the main chemicals present in one of the largest industrial accidents in the United States. We investigated the association between serum PBB-153 levels and autoimmune disorders among members of the Michigan PBB Registry. MethodsEight hundred and ninety-five members of the registry had both a serum PBB-153 measurement and had completed one or more questionnaires about autoimmune disorders. Autoimmune disorders were examined collectively and within specific organ systems. Sex-stratified unadjusted and adjusted log-binomial models were used to examine the association between tertiles of serum PBB-153 levels and autoimmune disorders. Models were adjusted by lifestage at exposure (in utero, childhood, adulthood), smoking history (never, past, current), and total serum lipid levels (continuous). We utilized cubic spline models to investigate non-linearity between serum PBB-153 levels and the prevalence of autoimmune disorders. ResultsApproximately 12.9% and 20.7% of male and female participants reported having one or more autoimmune disorders, respectively. After adjustment for potential confounders, we observed no association between PBB-153 tertiles and the composite classification of ‘any autoimmune disorder’ in either sex. We observed some evidence for an association between serum PBB-153 levels and rheumatoid arthritis in males and females; however, this was not statistically significant in females. We also observed some evidence for an association between serum PBB-153 levels and neurological- and thyroid-related autoimmune disorders in females, but again this was not statistically significant. Additionally, we identified dose-response curves for serum PBB-153 levels and the prevalence of autoimmune disorders that differed by lifestage of exposure and sex. ConclusionsWe observed some evidence that increasing serum PBB-153 levels were associated with three specified autoimmune disorders. Studies focusing on these three autoimmune disorders and the potential non-linear trend differences by lifestage of exposure warrant further investigation.

Toxic effects of Tripterygium glycoside tablets on the reproductive system of male rats by metabolomics, cytotoxicity, and molecular docking

BackgroundTripterygium glycoside tablets (TGT) is the most common preparation from Tripterygium wilfordii Hook F, which is widely used in clinical for treating rheumatoid arthritis (RA) and other autoimmune diseases. However, its serious reproductive toxicity limits its application. PurposeThis study aimed to elucidate the toxic effects of TGT on the reproductive system of male RA rats and its potential toxic components and mechanism. MethodsCollagen-induced arthritis (CIA) rat model was established, and TGT suspension was given at low, medium, and high doses. Gonadal index, pathological changes, and the number of spermatogenic cells were used to evaluate the toxic effects of TGT on the reproductive system. Non-targeted metabolomics of testicular tissue was conducted by UHPLC-QTOF/MS. Combined with network toxicology, the key targets of TGT-induced reproductive toxicity were screened and RT-qPCR was used to validation. In vitro toxicity of 19 components of TGT was evaluated using TM3 and TM4 cell lines. Molecular docking was used to predict the interaction between toxic components and key targets. ResultsTGT reduced testicular and epididymis weight. Pathology analysis showed a lot of deformed and atrophic spermatogenic tubules. The number of spermatogenic cells decreased significantly (P<0.0001). A total of 58 different metabolites including platelet-activating factor (PAF), lysophosphatidylcholine (Lyso PC), phosphatidylinositol (PI), glutathione (GSH), and adenosine monophosphate (AMP) were identified by testicular metabolomics. Glycerophospholipid metabolism, ether lipid metabolism, and glutathione metabolism were key pathways responsible for the reproductive toxicity of TGT. Ten key reproductive toxicity targets were screened by network toxicology. The cytotoxicity test showed that triptolide, triptonide, celastrol, and demethylzeylasteral could significantly reduce the viability of TM3 and TM4 cells. Alkaloids had no apparent toxic effects. Molecular docking showed that the four toxic components had a good affinity with 10 key targets. All binding energies were less than -7 kcal/mol. The RT-qPCR results showed the Cyp19a1 level was significantly up-regulated. Pik3ca and Pik3cg levels were significantly down-regulated. ConclusionThrough testicular metabolomics, we found that TGT may cause reproductive toxicity through CYP19A1, PIK3CA, and PIK3CG three target, which was preliminarily revealed. This study laid the foundation for elucidating the toxicity mechanism of TGT and evaluating its safety and quality.

Association between vitamin D level in rheumatoid arthritis in males and females

Rheumatoid Arthritis is an autoimmune disease of unknown aetiology. The worldwide prevalence of rheumatoid arthritis is estimated to vary between 0.5 to 1.5% with geographic variation. The rationale behind relating vitamin D and RA is based on two facts. The first one is that there is evidence indicating that patients with RA have low levels of vitamin D. The second one is that the presence of vitamin D and VDR in macrophages, chondrocytes and synovial cells in the joints of these patients has also been demonstrated. The present study was designed to study the vitamin D status/ level in rheumatoid arthritis in males and females. The study was carried on 100 subjects chosen randomly with 75 females and 25 males in age group of 16 – 65 years. Their demographic data was collected. Vitamin D level, rheumatoid factor assay and ESR were analyzed. Higher level of disease activity as measured by DAS 28 score was associated with vitamin D deficiency. Females reported higher values for ESR, DAS 28 score and lower levels of vitamin D level as compared to males.Vitamin D deficiency was positively associated with increase in DAS 28 score and rheumatoid arthritis (RA). Female sex had more preponderance for RA development. Rheumatoid factor had no gender preponderance.

Potential Cancer Risk in Patients with Rheumatoid Arthritis: A Longitudinal Korean Population-Based Analysis.

The potential link between rheumatoid arthritis (RA) and cancer incidence needs to be validated due to inconsistent results between Asian and Western countries. We explored the long-term association of RA with the overall and organ-specific cancer incidence using nationwide population data. This longitudinal follow-up study (2002–2015) included 3070 patients with RA and 12,280 controls (1:4 propensity score-matched for sex, age, residence, and income) from the Korean National Health Insurance Service-Health Screening Cohort database. A Cox proportional hazard model estimated the hazard ratio for malignancy following adjusting for covariates. Despite the similar overall cancer incidence between RA and control groups, differences in the incidence of organ-specific cancers were noted: the RA group had a 1.63-fold greater likelihood for lung cancer (95% confidence interval 1.11–2.40). In the sex-stratified subgroup analyses, the male RA patients exhibited higher odds of lung and thyroid cancer but a lower probability for colorectal cancer; no such associations were detected in either female patients with RA or age subgroups. In summary, the higher likelihood for lung cancer in Korean RA patients, especially thyroid and lung cancer in male RA patients, seems to be characteristic, which needs to be carefully monitored.

Tofacitinib monotherapy and erectile dysfunction in rheumatoid arthritis: a pilot observational study.

We aimed to explore the effect of tofacitinib on erectile dysfunction (ED), as well as disease activity and health related quality of life in male patients with rheumatoid arthritis (RA). Forty eight male RA patients with ED were included. Demographic and clinical data at baseline and 6 month of treatment were recorded from patients' medical records. Disease activity was evaluated with the disease activity score on 28 joints (DAS28), quality of life with Health Assessment Questionnaire-Disability Index (HAQ-DI) and ED with International Index of Erectile Function-5 (IIEF-5). The patients were aged 45.58 [Formula: see text] 2.14years with a disease duration of 79.33 [Formula: see text] 25.31months. According to the IIEF-5, 17 (35.4%) patients had severe ED, 10 (20.8%) patients moderate ED, 10 (20.8%) patients mild to moderate ED and 11 (22.9%) patients mild ED. For the entire patient group, baseline median IIEF-5 score was significantly increased from 9.35 (5.30-19.40) to 9.90 (5.20-24.90), baseline median DAS28 was significantly decreased from 5.65 (4.80-6.70) to 5.00 (2.40-6.40), HAQ-DI from 1.70 (1.10-2.40) to 1.15 (0.40-2.20) at 6th month of treatment (all p value < 0.001). Also, quantitative change in IIEF-5 was significantly correlated with changes in DAS28 (r:-0.735, p < 0.001) and HAQ-DI (r: -0.700, p < 0.001). Tofacitinib monotherapy may improve ED severity and as well as disease activity and health related quality of life in male patients with RA complaining of ED.

Composition of the body in male patients with rheumatoid arthritis with account of androgenic status

Aim. To evaluate alterations in body composition and bone mineral density (BMD) in male patients with rheumatoid arthritis (RA) taking into account their androgen status. Materials and methods. The single-stage study included 96 male RA patients. The mean age of patients was 59 [54; 64.75] years. The control group included 30 healthy men of comparable age. The androgen status assessment was based on sex hormone binding globulin (SHBG), total and free testosterone levels determination. Body composition and BMD measurements were performed using dual-energy X-ray absorptiometry (DXA) on the Stratos dR device (DMS, France) with the program “Whole Body”. Depending on the combination of BMD, lean- and fat-mass parameters, phenotypes of body composition were determined. The study was approved by Pirogov Russian National Research Medical University Local Ethics Committee. All patients signed informed consent.Results. Generally, lumbar spine, femoral neck and total hip BMD in RA patients was significantly less than in the control group (p&lt;0.05). In 69 (71.9%) patients with RA osteopenic syndrome was detected. It was represented by osteopenia and osteoporosis (OP) in 60.4% and 11.5% of cases respectively. The spine and femoral neck BMD correlated negatively with SHBG level, and positive correlation was detected between BMD and free testosterone level. The RA patients had significantly less lean mass than the control group. Low lean mass was found in 48.9% of patients in the main group and was not detected in the control group. Appendicular lean mass (ALM) correlated positively with total and free testosterone levels. According to DXA data, the adipose tissue content (%) corresponded to obesity in 63.3% of patients. Adipose tissue indicators correlated negatively with SHBG, total and free testosterone levels. The BMD of various skeleton parts correlated positively with trunk lean mass, and the femoral neck and total hip BMD had positive relationships with body mass index (BMI). Body composition alterations were revealed in 93.2% of RA patients. The most common phenotypes were osteosarcopenic obesity (25%), osteopenic obesity (21.6%) and osteopenic sarcopenia (14.8%). Conclusion. Our study shows that RA course in men is associated with the development of osteopenic syndrome in 71.9% of cases and ALM decrease to diagnostic values of sarcopenia in 48.9% of cases. This fact should be considered in the development of a gender approach to RA patients management and rehabilitation.

Guideline-based Treatment of Glucocorticoid-induced Osteoporosis in Patients with Rheumatoid Arthritis: A Retrospective Study with the AORA Registry.

Glucocorticoid-induced osteoporosis (GIOP) is one of the side effects associated with glucocorticoid (GC) therapy. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) provided new guidelines for the management and treatment of GIOP. The aim of the present study was to clarify the prevalence of patients with rheumatoid arthritis (RA) requiring treatment according to the new guidelines and to identify risk factors associated with lack of treatment in these patients. Patients in the 2018 Akita Orthopedic group on Rheumatoid Arthritis (AORA) database were enrolled. Of 2,234 patients with RA in the database, 683 (30.6%) met the 2014 JSBMR guideline treatment criteria, and 480 (70.3%) had been treated. The untreated group included a larger number of males, younger patients, and patients treated in clinics rather than hospital (p<0.001, p=0.015, and p<0.001, respectively). Multivariate analyses found that male sex, younger age, and clinic-based RA care were significant risk factors associated with lack of treatment (p<0.001, p=0.013, and p<0.001, respectively). Thus, male sex, younger age, and clinic-based care were identified as risk factors.

The impact of sex on susceptibility to systemic lupus erythematosus and rheumatoid arthritis; a bioinformatics point of view

The unknown etiology of systemic autoimmune diseases, such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA), with a remarkable predominance of female, have prompted many researchers for unveiling the precise molecular mechanisms involved in this gender bias. In fact, depending on hormones and transcribed genes from sex chromosomes, at least, the initial mechanisms involved in pathogenesis might differ largely. With the aim of elucidating the above mechanisms, we have tried to specify the differentially expressed genes (DEGs) extracted from microarray libraries from both female and male SLE and RA patients. Subsequently, the androgen and estrogen receptor elements (ARE and ERE) among differentially expressed transcription factors (TFs) and the DEGs located on X or Y chromosomes have been determined. Moreover, the pathways regarding the common DEGs in both sexes are enriched. Our data revealed several ARE and ERE-containing genes (LCN2, LTF, RPL31, RPL9, RPS17, RPS24, RPS27L, S100A8, ABCA1, HIST1H2BD, ISG15, MAFB, GNLY, EVL, and HDC) to be associated with the related autoimmune disease and sex. Also, two DEGs (KDM5D and RPS4Y1) in SLE patients were determined to be on Y chromosome with one had been proved to be associated with autoantigens in SLE. Altogether, our data showed a number of plausible pathways in both autoimmune conditions together with the relevance of several sex-related genes in the mentioned diseases pathogenesis.

Decrease in handgrip strength in rheumatoid arthritis (RA): is there a sex-related difference?

Rheumatoid arthritis occurs two to three times more often in women than in men and it has been less studied in men. The results of gender influence on clinical course of the disease are contradictory. The aim of this study is to determine the difference in handgrip strength between female and male RA patients in comparison to healthy individuals. The study included 100 RA patients and 100 healthy individuals (50% were male in both groups). Handgrip strength was measured in both hands using a dynamometer. A two-way ANCOVA was used to analyse the data and age was included in the study as covariate. The results show that both male and female RA patients have lower handgrip strength compared to healthy individuals. The analysis of gender and disease interaction has shown that male RA patients have lower handgrip strength than female RA patients in comparison with the healthy group, age adjusted. This interaction is evident and statistically significant in both right hand (F 1, 195) = 14.62; p < 0.01) and left hand (F 1, 195) = 20.54; p < 0.01). The common-language effect size has shown that there is 92% (right hand) and 93% (left hand) chance that male individual will have stronger handgrip than his female counterpart. In RA patients, there is 77% chance for both hands that male will have stronger handgrip. Men and women with RA have significantly lower handgrip strength compared to healthy individuals and the difference is more pronounced in men which was not previously observed in the literature.

Correlation of osteoarthritis or rheumatoid arthritis with bone mineral density in adults aged 20\u201359 years

BackgroundIt is reported that osteoporosis commonly occurs among patients with rheumatoid arthritis (RA), whereas the association between osteoporosis and osteoarthritis (OA) remains controversial. Our aim in this study was to investigate the association between BMD, as a marker of osteoporosis, and OA and RA among adults 20−59 years of age, using a population-based sample from the National Health and Nutrition Examination Survey (NHANES).MethodsOur analysis was based on the NHANES data collected between 2011 and 2018. Data regarding arthritis status and the type of arthritis (OA or RA) were obtained from questionnaires. Lumbar BMD was measured by dual-energy X-ray absorptiometry. The association between OA, RA, and lumbar BMD was evaluated using logistic regression models. Subgroup analyses, stratified by gender and race, were performed. The association between duration of arthritis and lumbar BMD was also investigated.ResultsA total of 11,094 adults were included in our study. Compared to the non-arthritis group, participants with OA had a higher lumbar BMD (β = 0.023, 95% CI 0.011–0.035), with no significant association between lumbar BMD and RA (β = 0.014, 95% CI − 0.003 to 0.031). On subgroup analyses stratified by gender, males with OA had a higher lumbar BMD compared to those without OA (β = 0.047, 95% CI 0.028–0.066). In females, OA was not associated with lumbar BMD (β = 0.007, 95% CI − 0.008 to 0.021). There was no association between lumbar BMD and RA in both males (β = 0.023, 95% CI − 0.003 to 0.048) and females (β = 0.008, 95% CI − 0.015 to 0.031). Duration of arthritis was not associated with lumbar BMD for both OA (β = − 0.0001, 95% CI − 0.0017 to 0.0015) and RA (β = 0.0006, 95% CI − 0.0012 to 0.0025).ConclusionsLumbar BMD was associated with OA but not with RA. While a higher lumbar BMD was associated with OA in males, but not in females. Our findings may improve our understanding between OA, RA, and bone health.

Association of P2X7 receptor genetic polymorphisms and expression with rheumatoid arthritis susceptibility in a sample of the Iranian population: a case-control study.

Rheumatoid arthritis (RA) is a complex inflammatory autoimmune disease with joint eruption, systemic manifestation, and numerous predisposing genetic factors. The P2X7 receptor is an essential ligand-gated channel that contributes to many physiological processes, especially inflammation. However, genetic variations can alter the P2X7 receptor function. Therefore, the present study aimed to explore the impact of P2X7 genetic polymorphisms and expression on susceptibility to RA in a sample of the Iranian population. We enrolled 160 (145 female, 15 male) RA patients and 160 (142 female, 18 male) healthy individuals in this study. Genotyping was performed using tetra amplification refractory mutation system-polymerase chain reaction (TARMS-PCR) for rs1718119, rs2230912, rs2393799, rs28360457, rs35933842, and allele-specific PCR for rs1653624 and rs3751143. Furthermore, 44 new cases of RA and 48 healthy controls were recruited to investigate whether P2X7 mRNA expression is associated with RA susceptibility. The results revealed that the rs2393799 significantly increased the risk of RA in all genetic models (p<0.05), while rs3751143 in codominant (CC vs. AA, OR=0.49, 95% CI=0.26-0.92), dominant (AC+CC, OR=0.59, 95% CI=0.37-0.94), C allele (OR=0.63, 95% CI=0.46-0.88), and rs2230912 in codominant (AG vs. AA, OR=0.56, 95% CI=0.34-0.94), dominant (AG+GG vs. AA, OR=0.59, 95% CI=0.35-0.99), and overdominant (AG vs. AA+GG, OR=0.57, 95% CI=0.33-0.98) significantly decreased the RA risk (p<0.05). Furthermore, the rs1718119 and rs1653624 were not associated with susceptibility of RA (p>0.05), and rs28360457 and rs35933842 were not polymorphic in our study. The mRNA expression level of P2X7 in both groups revealed that the P2X7 gene was significantly upregulated in RA (3.18±0.43) compared to healthy subjects (1.47±0.15, p<0.001). Our results suggest that rs2393799, rs3751143, and rs2230912 variants of the P2X7 gene are associated with RA's susceptibility in a sample of the Iranian population. Also, P2X7 mRNA expression was higher in our new RA patients. The P2X7 receptor has been considered as a potential pharmacologic target in RA. Key Points • P2X7 variants (rs2393799, rs2230912, rs3751143) were associated with RA susceptibility in a sample of the Iranian population. • rs2393799 increases the risk of RA, while rs2230912 and rs3751143 decrease the risk of RA. • P2X7 expression was significantly upregulated in new RA patients compared to controls.

Gender Differences in Rheumatoid Arthritis: Interleukin-4 Plays an Important Role.

Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical peripheral polyarthritis. A large number of studies have shown that RA is characterized by gender differences in clinical manifestations. The purpose of this study is to identify the key molecules of gender differences in patients with RA and to provide new molecular targets for personalized therapy. Material and Methods. The data from GSE55457 were downloaded from the comprehensive gene expression comprehensive database, and two groups (RA vs. No-RA groups, Male-RA vs. Female-RA groups) of differentially expressed genes (EDGs) were obtained by GEO2R. The GO function and KEGG pathway analyses of DEGs were carried out through the plug-in ClueGO in Cytoscape. Based on the STRING online, a protein-protein interaction (PPI) network was constructed. Hub genes were selected from CytoHubba. Through the intersection of the top 10 hub genes in two sets of EDGs, the key genes and related KEGG pathways were found. Quantitative Real-Time PCR and Western blotting analysis were performed for verification. Results 1230 DEGs were screened between RA and No-RA groups, and 306 DEGs were screened between male and female RA groups. The common key gene of the two groups is IL-4. Between RA group and No-RA group, interleukin-4 (IL-4) participates in cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, Th17 cell differentiation, T cell receptor signaling pathway, etc. Conclusion This study contributes to the molecular biological mechanism of gender differences in RA. IL-4 may have played an important role.

Impact of Sex on Clinical Response in Rheumatoid Arthritis Patients Treated With Biologics at Approved Dosing Regimens.

The prevalence of rheumatoid arthritis (RA) is higher in females than in males. With the development of new treatment options and strategies such as biologics, we found it worthwhile to identify whether males and females warrant different treatment regimens to ensure the best clinical response. Our meta-analysis included 11 clinical trials of RA patients in support of the Food and Drug Administration's approval of 6 biological products. We evaluated the data of American College of Rheumatology 20 (ACR20) 24 or 26 weeks after treatment. Logistic regression models were applied to compute the odds ratio (OR) of treatment responses between sexes. The ORs of ACR20 response rates in males and females were similar across all studies and not significantly different in overall studies (OR, 1.05; 95% confidence interval, 0.96-1.16) analyzed with a fixed-effects model. Further analyses on the 7 ACR20 subcomponents showed high heterogeneity among studies (Q statistic P < .00007, I2 > 95%), with no observed clinically meaningful sex-related difference. Thus, our meta-analysis did not find significant difference in ACR20 response rates between male and female RA patients treated with biologics at approved dosing regimens. This result supports the current clinical practice of not requiring sex-dependent treatment regimens for RA patients.

Association of NCF2, NCF4, and CYBA Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population.

Objective Recent studies have focused on the special roles of NADPH-oxidase in multiple autoimmune diseases. Nevertheless, the association of genetic variation in NADPH-oxidase genes with rheumatoid arthritis (RA) was not extensively studied in a Chinese population. We performed this study to examine the association of NCF2, NCF4, and CYBA gene polymorphisms with RA susceptibility in a Chinese population. Methods Six single nucleotide polymorphisms (SNPs) (NCF2 rs10911363, NCF4 rs1883112, rs4821544, rs729749, CYBA rs3794624, and rs4673) were genotyped in a cohort composed of 593 RA patients and 596 normal controls. Improved multiple ligase detection reaction (iMLDR) was used for genotyping. Results We observed that NCF4 rs4821544 CT genotype and C allele frequencies in RA patients were significantly decreased when compared to controls (CT vs. TT: P = 0.043; C vs. T: P = 0.031), and rs4821544 polymorphism was significantly associated with an increased RA risk under the dominant model (TT vs. CT+CC: P = 0.031). Our results also indicated that rs729749 CT genotype frequency was significantly lower in RA patients than that in controls (CT vs. CC: P = 0.033). Moreover, the rs729749 CT genotype frequency was also significantly decreased in RA patients in males (CT vs. CC: P = 0.024). No significant association between NCF2 and CYBA gene polymorphisms and RA susceptibility was observed. There were significant associations between rs4821544 TT genotype and T allele frequencies and anti-CCP in male RA patients. Conclusions In summary, NCF4 rs4821544 and rs729749 polymorphisms might contribute to RA susceptibility, while NCF2 and CYBA gene polymorphisms were not associated with RA susceptibility.

Assessment of interleukin 6 gene polymorphisms with rheumatoid arthritis.

Rheumatoid arthritis (RA) is complex autoimmune system disease and significant impact on the health of population in our world. Numerous studies confirmed that genetic factors play a crucial role in the pathogenesis of RA. In this current study, we aimed to investigate IL-6 polymorphisms and RA risk in Chinese Han population. 508 RA patients and 494 age- and gender- matched healthy controls were recruited, all subjects were genotyped with an Agena MassARRAY platform. Subsequently, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression after adjusting for age and gender. Our results suggested that IL-6 rs2243289 allele and genotype frequencies were associated with reduced RA risk under all genetic models (all p<0.05). Stratification analysis revealed that IL-6 rs2243289 polymorphism was significant associated with decreased the risk of RA in the old groups (age>54) (all p<0.05). However, IL-6 rs2069837 and rs1800796 polymorphisms were associated with increased risk of RA among the young groups (age≤54) (all p<0.05). In addition, subgroup analysis by gender suggested that IL-6 rs2069837 and rs1800796 polymorphism were interacted with increased the risk of RA in males (all p<0.05). Besides, IL-6 rs2243289 was associated with reduced RA risk in females. In conclusion, our results demonstrated the correlation between IL and 6 polymorphisms and RA susceptibility and confirmed for the first time that the relationship was restricted to age and gender in Chinese Han population.

Osteoporosis in patients with rheumatoid arthritis: trends in the German National Database 2007\u20132017

Osteoporosis is a frequent comorbidity in rheumatoid arthritis (RA). Due to the improved treatment options for RA, we expect a long-term decrease in osteoporosis as an accompanying disease. Data from the German National Database (NDB) were used to investigate whether the frequency of osteoporosis has changed in the last 10 years. From 2007 to 2017, approximately 4000 patients were documented annually with data on therapy and comorbidity. The cross-sectional data were summarised descriptively. Age, sex, disease duration, disease activity and glucocorticoids were considered as influencing factors. The Cochrane-Armitage test for trend was used to test whether the frequency of osteoporosis at the first visit changed from 2007 to 2017. Osteoporosis frequency in RA patients (mean age 63 years, 75% female) decreased from 20% in 2007 to 6% in 2017 (p < 0.001). The decrease affected women (22% to 17%) and men (14% to 8%) in all age groups and both short-term (≤ 2-year disease duration: 9% to 3%) and long-term RA patients (> 10-year disease duration: 28% to 20%). Patients with high disease activity and patients who took glucocorticoids (GC) were more often affected by osteoporosis than patients in remission or without GC. Drug prophylaxis in patients without osteoporosis increased (20% to 41% without GC, 48% to 55% with GC). Men with GC received less prophylactic treatment than women (48% vs. 57% in 2017). In this cohort, osteoporosis in patients with RA is less frequently observed compared to former years. RA-specific risk factors for osteoporosis such as disease activity and GC therapy have declined but long-term GC use is still present. Assessment of osteoporosis in RA patients should be investigated more consistently by bone density measurement. Male RA patients still need to be given greater consideration regarding osteoporosis drug prophylaxis, especially when GC therapy is needed.