Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
35568442 Drugs Recommended in Adult Rheumatic Diseases, But Considered for Off-Label Use in Argenti 2022 May BACKGROUND: Off-label (OL) drug use is the prescription of a drug for indications other than those authorised in its technical datasheet. The objective of this study was to identify drugs recommended in rheumatology but considered for off-label use in Argentina. METHODS: A list of medications for certain selected rheumatic conditions was compiled. A drug was considered recommended if it was endorsed by a) at least one Argentine or Pan-American treatment guideline or consensus, or b) two international treatment guidelines, or c) one international treatment guideline and one selected textbook. Approval of these drugs for any condition in Argentina until December 31st, 2018 was explored, and medicines were divided into those with on-label indications and those considered for OL use. RESULTS: One hundred and thirty-six medications were analysed in 13 clinical conditions. Sixty-seven OL recommendations (49%) were found, and several drugs had more than one. All the conditions included the recommendation of at least 1 OL drug except osteoporosis and rheumatoid arthritis. The frequency of OL recommendations for the following conditions was 100%: calcium pyrophosphate dihydrate crystal deposition disease, polymyalgia rheumatica, Sjögren syndrome, and systemic sclerosis. The drugs with the highest number of OL recommendations were methotrexate (in 7 conditions), and glucocorticoids and mycophenolate (in 4). There were 2 OL recommendations for rituximab and 1 for abatacept. CONCLUSIONS: Almost all the rheumatic disorders analysed involved the recommendation of at least 1 OL medication, and in 4 conditions all the recommendations were OL. Most OL drugs recommended in rheumatology are neither biological nor small-molecule therapies.
35193709 Transcriptome sequencing reveals core regulation modules and gene signatures of Zusanli ac 2022 Feb 22 BACKGROUND: The efficacy of moxibustion in treating rheumatoid arthritis is recognized, but its molecular mechanism is still unclear. This study aimed to characterize the molecular map and potential key genes in the process of different moxibustion warm at Zusanli acupoint treatment of adjuvant arthritis (AA) model. METHODS: AA rat model was induced by complete Freund's adjuvant (CFA) and then accessed by foot swelling and thermal hyperalgesia test. Transcriptome sequencing, series test of cluster (STC) and weighted gene co-expression network analysis (WGCNA) were used in this study. RESULTS: CFA-induced inflammation, foot swelling, and pain in AA rats were significantly improved by moxibustion warm. Differentially expressed genes (DEGs) were screened in nine different comparison groups and a total of 4535 DEGs were identified, and these DEGs were preferentially clustered in inflammatory and immune-related pathways, such as MAPK signaling pathway. Only 1 DEG of heat shock protein 90, alpha (cytosolic), class A member 1 (Hsp90aa1) was shared in comparison groups of model with moxibustion treatment. STC analysis also revealed that Hsp90aa1 was increased in AA model, but decreased after 37 °C moxibustion intervention, and constantly decreased after 42 °C moxibustion treatment. GO and KEGG pathway analysis revealed that these genes enriched in inflammatory and immune-related pathways. Moreover, WGCNA identified that violet module was positively correlated with model temperature while negatively correlated with control, and the paleturquoise module was positively correlated with model. The violet and paleturquoise module gene were significantly enriched in MAPK signaling pathway. Importantly, Hsp90aa1 also played a central role in the violet module by interacting with multiple proteins. CONCLUSIONS: Moxibustion warm improved AA in rat, and we obtained the transcriptome profile and excavate a critical gene of Hsp90aa1, and provided insight into gene signatures for moxibustion warm at Zusanli acupoint in AA rat.
35633572 The influence of patient´s perspective in therapeutic adherence in rheumatoid arthritis : 2022 Jan OBJECTIVES: The main objective is to study the contribution of illness and medication beliefs to treatment adherence in patients with rheumatoid arthritis. METHODS: the design was a cross-sectional study. The compliance Questionnaire for Rheumatology (CQR) was used to measure therapeutic adherence. The beliefs about medicines questionnaire (BMQ) and the brief illness perception questionnaire (IPQ-b) were used to assess patient's beliefs about medicines and about the disease. Other factors studied were treatment satisfaction, patient´s demographic and clinical characteristics. RESULTS: 144 patients were included in the study, 113 (78.4%) patients showed good treatment adherence. Patients with poor adherence presented higher scores in the BMQ harm domain (13±5 vs. 11±3, p= 0.013). Meanwhile, patients with good adherence presented higher scores in the necessity BMQ domain (21±3 vs. 20±3, p= 0.015), increased feeling of treatment control (8.8± 1.5 vs. 7.7± 2.1,p= 0.008), higher emotional response (6.2±3.1 vs. 4.8±3.4,p= 0.042) and a higher level of treatment satisfaction (77.2±12.4 vs. 69.9±12.5,p=0.004). In a multivariate analysis for each unit of increase in the score of BMQ´s harm domain, adherence was reduced by 20% (CI 95% 0.08-0.3, p= 0.001); for each unit of increase in treatment control item of the IPQ-b, adherence increased 1.4 times (CI 95% 1.1-1.8,p= 0.006); and for each unit of increase in the emotional response item of the IPQ-b, adherence increased 1.3 times (CI 95% 1.1-1.5,p= 0.002). CONCLUSION: in our cohort of RA patients, good adherence is associated with stronger treatment necessity perception, stronger feeling of treatment control, higher emotional response and higher level of treatment satisfaction; on the other side, patients with poor adherence had stronger beliefs of medicines as harmful substances.
34555458 Serum and Synovial Biomarkers for Distinguishing Between Chronic Periprosthetic Joint Infe 2022 Feb BACKGROUND: Inflammatory responses in patients with active rheumatoid arthritis (RA) may lead to the current serum and synovial fluid biomarkers that misidentify chronic periprosthetic joint infection (PJI). We sought to investigate the expression of serum and synovial biomarkers in patients with active RA and to calculate thresholds for valuable biomarkers that distinguish between chronic PJI and active RA. METHODS: This prospective study was initiated to enroll 70 patients undergoing revision arthroplasty from January 2019 to January 2021, and 30 patients with active RA cumulative knee from August 2020 to March 2021. The Musculoskeletal Infection Society definition of PJI was utilized for the classification of cases as aseptic or infected. Serum d-dimer, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6 (IL-6), as well as synovial IL-6, percentage of polymorphonuclear neutrophils, and CD64 index level were measured preoperatively. RESULTS: An increase in biomarker concentrations were observed in group C (active RA). Synovial fluid CD64 index exhibited good discriminatory power between group B (chronic PJI) and group C with an area under curve of 0.930. For the diagnosis of chronic PJI in the presence of active RA, the optimal threshold value of synovial CD64 index was 0.87, with a sensitivity of 82.86% and a specificity of 93.33%. CONCLUSION: Current serum biomarkers (erythrocyte sedimentation rate, C-reactive protein, IL-6, and d-dimer) did not apply to the diagnosis of suspected PJI with active RA. Fortunately, satisfactory results can be achieved by adjusting the threshold of synovial fluid biomarkers.
35527655 Therapeutic effects of acupuncture in rheumatoid arthritis are associated with centromere 2022 OBJECTIVE: The objective of this study is to study the critical role of CENPF in regulation of rheumatoid arthritis with acupuncture treatment. METHODS: PCA was used to analyze the different expression genes between AP treatment group and control group. Volcano plot and random forest model were used to analyze the decreased and increased expression genes. RT-qPCR and IF were used to measure the expression of CENPF in CIA model rat with or without AP treatment. The expression of MCP-1, TNF-α and IL-6 was measured by western blotting. The pathology character and arthritis index were used to analyze the severity of joint injury. RESULTS: PCA data showed that the expression of genes was different between AP treatment group and control group from GEO datasets. Volcano plot and random forest model analysis indicated that CENPF is the most significantly increased expression gene after AP treatment. RT-qPCR and IF assay showed that CENPF is reduced expression in CIA model rat, while CENPF is upregulated expression in CIA model rat with AP treatment. Furthermore, overexpression of CENPF reduced the increasing of MCP-1, TNF-α and IL-6 in CIA model rat. On the contrary, CENPF deficiency induced the expression of MCP-1, TNF-α and IL-6 in CIA model rat. Additionally, the expression of MCP-1, TNF-α and IL-6 in CIA model rat was suppressed, whereas knockdown of CENPF antagonized the decrease of MCP-1, TNF-α and IL-6 in CIA model rat with AP treatment. CONCLUSIONS: CENPF may be a key gene in regulation of the therapeutic effects of acupuncture in rheumatoid arthritis. Rheumatoid arthritis is a globally common autoimmune inflammatory disease found especially in China. Acupuncture (AP), a traditional Chinese medicine (TCM) treatment method, is commonly used for treating rheumatoid arthritis. Many studies have demonstrated that acupuncture alone or in combination with other treatments is beneficial to treat clinical situation of rheumatoid arthritis, thus improving function and quality of life. In this study, we found that centromere protein F (CENPF) is a key gene in rheumatoid arthritis with acupuncture treatment by using differentially expressed genes (DEGs) and random forest model analysis of GSE57983 and GSE77298. Acupuncture helps to up-regulate the expression of CENPF in tissues in rheumatoid arthritis. Functionally, overexpression of CENPF inhibits monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and Interleukin (IL)-6 expressions whereas deficiency of CENPF facilitates MCP-1, TNF-α, and IL-6 expressions in a collagen-induced arthritis (CIA) rat model. Furthermore, knocked down CENPF with acupuncture treatment antagonizes the inhibition of MCP-1, TNF-α, and IL-6 expressions in a CIA rat model. CENPF could be a crucial biomarker in regulating function of acupuncture in treating rheumatoid arthritis.
35115492 TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induc 2022 Feb 3 Ferroptosis is a nonapoptotic cell death process that requires cellular iron and the accumulation of lipid peroxides. In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate abnormally in the presence of reactive oxygen species (ROS) and elevated lipid oxidation. Here we show, using a collagen-induced arthritis (CIA) mouse model, that imidazole ketone erastin (IKE), a ferroptosis inducer, decreases fibroblast numbers in the synovium. Data from single-cell RNA sequencing further identify two groups of fibroblasts that have distinct susceptibility to IKE-induced ferroptosis, with the ferroptosis-resistant fibroblasts associated with an increased TNF-related transcriptome. Mechanistically, TNF signaling promotes cystine uptake and biosynthesis of glutathione (GSH) to protect fibroblasts from ferroptosis. Lastly, low dose IKE together with etanercept, a TNF antagonist, induce ferroptosis in fibroblasts and attenuate arthritis progression in the CIA model. Our results thus imply that the combination of TNF inhibitors and ferroptosis inducers may serve as a potential candidate for RA therapy.
34435471 Effect of JAK Inhibition on the Induction of Proinflammatory HLA-DR+CD90+ Rheumatoid Arthr 2022 Mar OBJECTIVE: Findings from recent transcriptome analyses of the synovium of patients with rheumatoid arthritis (RA) have revealed that 15-fold expanded HLA-DR+CD90+ synovial fibroblasts potentially act as key mediators of inflammation. The reasons for the expansion of HLA-DR+CD90+ synovial fibroblasts are unclear, but genetic signatures indicate that interferon-γ (IFNγ) plays a central role in the generation of this fibroblast subset. The present study was undertaken to investigate the generation, function and therapeutically intended blockage of HLA-DR+CD90+ synovial fibroblasts. METHODS: We combined functional assays using primary human materials and focused bioinformatic analyses of mass cytometry and transcriptomics patient data sets. RESULTS: We detected enriched and activated Fcγ receptor type IIIa-positive (CD16+) NK cells in the synovial tissue from patients with active RA. Soluble immune complexes were recognized by CD16 in a newly described reporter cell model, a mechanism that could be contributing to the activation of natural killer (NK) cells in RA. In vitro, NK cell-derived IFNγ induced HLA-DR on CD90+ synovial fibroblasts, leading to an inflammatory, cytokine-secreting HLA-DR+CD90+ phenotype. HLA-DR+CD90+ synovial fibroblasts consecutively activated CD4+ T cells upon receptor crosslinking via superantigens. HLA-DR+CD90+ synovial fibroblasts also activated CD4+ T cells in the absence of superantigens, an effect that was initiated by NK cell-derived IFNγ and that was 4 times stronger in patients with RA compared to patients with osteoarthritis. Finally, JAK inhibition in synovial fibroblasts prevented HLA-DR induction and blocked proinflammatory signals to T cells. CONCLUSION: The HLA-DR+CD90+ phenotype represents an activation state of synovial fibroblasts during the process of inflammation in RA that can be induced by IFNγ, likely generated from infiltrating leukocytes such as activated NK cells. The induction of these proinflammatory, interleukin-6-producing, and likely antigen-presenting synovial fibroblasts can be targeted by JAK inhibition.
34697722 LASSBio-596: a New Pre-clinical Candidate for Rheumatoid Arthritis? 2022 Apr Pain and inflammatory disorders are significant health problems because of prevalence and associated disabilities. In this context, LASSBio-596 is a hybrid compound able to modulate TNF-α and phosphodiesterases 4 and 5, exhibiting an anti-inflammatory effect in the pulmonary inflammatory model. Aiming at a better description of the activities of LASSBio-596, we initially conducted nociception tests (acetic acid-induced abdominal writhing, glutamate, and formalin-induced nociception and hot plate test) and later inflammatory tests (acute, peritonitis; and chronic, arthritis) that directed us to this last one. In the abdominal writhing test, there was a dose-dependent inhibition, whose response occurred at the maximum dose (50 mg/kg, p.o.), used in the subsequent tests. LASSBio-596 also inhibited nociception induced by chemical (glutamate by 31.9%; and formalin, in both phases, 1st phase: 25.7%; 2nd phase: 23.9%) and thermal agents (hotplate, by increased latency for pain at two different times). These effects were independent of the motor function, legitimated in rotarod. As there was a response in the inflammatory component of nociception, we performed the peritonitis test, in which migration was inhibited by LASSBio-596 by 39.9%. As the inflammatory process is present in autoimmune diseases, we also performed the arthritis test. LASSBio-596 reduced paw edema from the 15th day to the 21st day of treatment (no liver changes and with fewer paw injuries). In addition, LASSBio-596 decreased serum levels of TNF-α by 67.1%. These data demonstrated the antinociceptive effect of LASSBio-596 and reinforces its anti-inflammatory property (i.e., RA), amplifying the therapeutic potential of this molecule.
35319537 Performance of the Rheumatoid Arthritis Disease Activity Index in the Assessment of Diseas 2022 Jun 1 BACKGROUND/OBJECTIVE: Although telemedicine use has been under discussion for decades, this topic has gained unprecedented importance during the COVID-19 pandemic. The Rheumatoid Arthritis Disease Activity Index (RADAI) is a user-friendly tool, fully self-administered, to assess rheumatoid arthritis (RA) disease activity. The aim of this study was to compare the performance of RADAI with other disease activity indices, functional status, and inflammatory markers in a large cohort of RA patients. METHODS: We assessed the concurrent validity of RADAI against Clinical Disease Activity Index (CDAI), Disease Activity Score in 28 Joints-C-reactive protein, Disease Activity Score in 28 Joints-erythrocyte sedimentation rate, Simplified Disease Activity Index, and physician assessment of disease activity and the correlation of RADAI with Health Assessment Questionnaire-Disability Index and inflammatory markers at the REAL Study baseline. We also evaluated the correlation of the change in RADAI and the change in CDAI over a 6-month follow-up. RESULTS: From the 1115 patients included in the REAL Study, 1113 had RADAI scores in the first assessment. At baseline, correlations between RADAI and other disease activity indices were strong, ranging from 0.64 (comparison with physician assessment) to 0.79 (comparison with CDAI). Correlation between the change in RADAI score over the 6 months of follow-up and the change in CDAI score over the same period was moderate/strong for the overall group and within the stratified analyses. CONCLUSION: The strong correlation of RADAI with other well-established tools for disease activity measurement reassures its use with RA patients' follow-up, especially in this new era of telemedicine.
35456038 Autophagy in Rheumatic Diseases: Role in the Pathogenesis and Therapeutic Approaches. 2022 Apr 15 Autophagy is a lysosomal pathway for the degradation of damaged proteins and intracellular components that promotes cell survival under specific conditions. Apoptosis is, in contrast, a critical programmed cell death mechanism, and the relationship between these two processes influences cell fate. Recent evidence suggests that autophagy and apoptosis are involved in the self-tolerance promotion and in the regulatory mechanisms contributing to disease susceptibility and immune regulation in rheumatic diseases. The aim of this review is to discuss how the balance between autophagy and apoptosis may be dysregulated in multiple rheumatic diseases and to dissect the role of autophagy in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome. Furthermore, to discuss the potential capacity of currently used disease-modifying antirheumatic drugs (DMARDs) to target and modulate autophagic processes.
35459111 Anti-neutrophil cytoplasmic antibody associated vasculitis in patients with rheumatoid art 2022 Apr 22 BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may coexist with rheumatoid arthritis (RA). However, it is unclear whether the manifestations of AAV with and without coexisting RA are similar. This observational study aimed to investigate the clinicopathological manifestations of AAV with coexisting RA and to explore potential predictors for identifying AAV superimposed on RA. METHODS: Patients with both AAV and RA were identified by searching our hospital database and the literature. Data including age, sex, clinical manifestation, laboratory tests, renal pathology, and therapeutic regimens were retrieved. To assess the difference in clinical features and renal pathology between AAV patients with and without RA, we conducted 1:4 matched case-control studies. RESULTS: A total of 47 patients were identified, 15 from our hospital and 32 from the literature, and 33 (70.2%) were women. AAV was diagnosed later than RA in 83.0% of the patients and manifested as microscopic polyangiitis (MPA) in 78.7% of the patients. The kidney was the most frequently involved extra-articular organ (74.5%), followed by the lung (51.1%), and skin (8.5%). Patients with both AAV and RA were more likely to be asymptomatic (26.7% vs 3.3%, p = 0.013) than those with isolated AAV. However, they did not differ in other clinicopathological features. In RA patients, those with ANCA associated glomerulonephritis, were more likely to have decreased renal function at renal biopsy as opposed to those with primary glomerulonephritis. CONCLUSIONS: AAV can coexist with RA. In this coexistence, AAV usually develops after RA, is more likely to be asymptomatic, and manifests predominately as MPA with renal involvement. Thus, we should remain vigilant to superimposed AAV on RA.
35171544 Study of transforming growth factor beta 1 gene +869T/C polymorphism in Egyptian rheumatoi 2022 Jan This study intended to explore the relationship between the +869T/C polymorphism of the transforming growth factor-β1 (TGF-β1) gene and rheumatoid arthritis (RA) predisposition and activity in Egyptian patients. The study involved 30 patients suffering from RA and 30 apparently healthy participants as the control group. The +869T/C polymorphism of the TGF-β1 gene was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) process. The TGF-β1 + 869 CT genotype and CT+TT genotypes in RA patients showed a significant increase than the control group (OR=3.782 and 3.824, CI=1.046-13.680 and 1.150-12.713, P=0.043 and 0.029, respectively). T allele showed a significant increase in patients than in controls (OR= 2.104, CI 1.015- 4.361, P = 0.046). The TGF-β1 +869 CT+TT genotypes were accompanied by higher DAS-28 scores which express higher disease activity, and increased levels of RF, Anti-CCP, ESR, and CRP. In conclusion, the TGF-β1 +869T/C gene polymorphism may be accompanied by an increased predisposition to RA and with its severity in Egyptian RA patients.
34132621 Degree of arterial stiffness is comparable across inflammatory joint disease entities. 2022 May OBJECTIVES: Inflammatory joint disease (IJD) is associated with an increased risk of developing cardiovascular disease (CVD). Arterial stiffness is both a risk factor and a surrogate marker for CVD. This study aims to compare arterial stiffness across patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and, by extension, to explore the relationship between arterial stiffness and the estimated CVD risk by the Systematic COronary Risk Evaluation (SCORE) algorithm. METHOD: During the study period, from April 2017 to June 2018, 196 patients with IJD visited the Preventive Cardio-Rheuma Clinic in Oslo, Norway. A CVD risk stratification was performed, including the assessment of traditional risk factors and the measurement of arterial stiffness. RESULTS: Thirty-six patients (18.4%) had elevated aortic pulse wave velocity (aPWV) (≥ 10 m/s). After adjustment for age and heart rate, arterial stiffness was comparable across the IJD entities (p = 0.69). Associated factors, revealed by regression analysis, were age, blood pressure, heart rate, presence of carotid plaques, establis hed CVD, non-steroidal anti-inflammatory drugs, and statin use. Furthermore, aPWV was positively correlated with estimated CVD risk (r = 0.7, p < 0.001) and patients with a very high predicted CVD risk (SCORE ≥ 10%) had significantly higher aPWV than patients at lower CVD risk (9.2 vs 7.5 m/s, p < 0.001). CONCLUSION: The degree of arterial stiffness was comparable across the IJD entities and was highly associated with the estimated CVD risk. Our findings support the need for an increased focus on prevention of CVD in all patients with IJD.
34097322 Adrenocortical dysfunction in rheumatoid arthritis: Α narrative review and future directi 2022 Jan BACKGROUND: Iatrogenic adrenal insufficiency (AI) secondary to long-term treatment with exogenous glucocorticoids (GC) is common in patients with systematic rheumatic diseases, including rheumatoid arthritis (RA). Moreover, a proportion of these patients is always in need of even small doses of glucocorticoids to maintain clinical remission, despite concomitant treatment with conventional and biologic disease-modifying drugs. METHODS: We conducted a literature review up to December 2020 on (a) the incidence of AI in both long-term GC-treated and GC-treatment naïve RA patients; (b) the potential effects of increased levels of circulating proinflammatory cytokines, as well as of chronic stress, in adrenocortical function in RA; (c) the circadian cortisol rhythm in RA; and (d) established and evolving methods of assessment of adrenocortical function. RESULTS: Up to 48% of RA patients develop glucocorticoid-induced AI; however, predictors are not established, while adrenocortical dysfunction may also occur in GC-treatment naïve RA patients. Experimental and clinical data have suggested that inadequate production of endogenous cortisol relative to enhanced clinical needs associated with the systemic inflammatory response, coined as the 'disproportion principle', may operate in RA. Although the underlying mechanisms are unknown, both proinflammatory cytokines and chronic stress may contribute the most in the adrenals hyporesponsiveness and the target tissue glucocorticoid resistance that have been described, but not systematically studied. A precise longitudinal assessment of endogenous cortisol production may be needed for optimal RA management. CONCLUSION: Apart from iatrogenic AI, an intrinsically compromised adrenal reserve in RA may have a pathogenetic role and interfere with effective management, thus deserving further research.
34046752 TGFB1 (rs1800470 and rs1800469) variants are independently associated with disease activit 2022 Feb To evaluate the association between TGFB1 + 869 T > C (rs1800470) and TGFB1-509 C > T (rs1800469) variants with susceptibility for rheumatoid arthritis (RA), disease activity, presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and TGF-β1 plasma levels. A total of 262 patients with RA and 168 control individuals were tested for the TGFB1 variants using a TaqMan genotyping assay. Disease activity score in 28 joints (DAS28) classified RA patients into two groups of disease activity: remission/mild (DAS28 < 3.2) and moderate/severe (DAS28 ≥ 3.2). TGFB1 + 869 T > C and -509 C > T variants, independently or in haplotype combination, were not associated with RA's susceptibility. Patients with the TGFB1-509 TT genotype had a higher frequency of DAS28 ≥ 3.2 (OR 2.58, 95% CI 1.04-6.42, p = 0.041). The TGFB1 + 869 CC genotype in seropositive patients for RF or anti-CCP was associated with decreased TGF-β1 levels (p = 0.032 and p = 0.039, respectively). Patients with the TGFB1 + 869 C allele and elevated RF titles demonstrated a higher frequency of DAS28 ≥ 3.2 (p = 0.037). The TGFB1 + 869 T > C variant was associated with diminished TGF-β1 plasma levels and moderate/severe activity disease only in seropositive RF patients. This is the first study showing that TGF-β1 plasma levels can be modulated by the interaction between the TGFB1 + 869 T > C variant and autoantibodies. However, the TGFB1-509 C > T variant was associated with moderate/severe activity disease, independently of autoantibodies positivity. Thus, our findings suggest that TGFB1 + 869 T > C and -509 C > T variants can predict activity disease in different RA patient subgroups.
34272604 Self-reported fatigue in patients with rheumatoid arthritis compared to patients with canc 2022 Feb Fatigue is a common symptom in patients with rheumatoid arthritis (RA) and in patients with cancer (CA). The aim was to investigate the degree of fatigue in RA patients as compared to CA patients as well as potential influencing factors on RA-related fatigue. This was a retrospective analyses of two prospective cohort studies that used the EORTC QLQ-FA12 as a common instrument to assess fatigue. The cohort of RA patients was based on a nationwide survey in Germany. The cohort of CA patients was recruited in the context of an international validation field study. Multivariable ANCOVAs compared levels of fatigue between the two cohorts, also including various subgroup analyses. Regression analyses explored influencing factors on RA patients' fatigue. Data of n = 705 RA patients and of n = 943 CA patients were available for analyses. RA patients reported significantly higher Physical Fatigue (mean difference = 7.0, 95% CI 4.2-9.7, p < 0.001) and Social Sequelae (mean difference = 7.5, 95% CI 4.7-10.2, p < 0.001). CA patients reported higher Cognitive Fatigue (mean difference = 3.5, 95% CI 1.4-5.6, p = 0.001). No differences in Emotional Fatigue (p = 0.678) and Interference with Daily Life (p = 0.098) were found. In RA patients, mental health and pain were associated with fatigue (p values < 0.001). RA patients showed a considerable level of fatigue that is comparable to and in certain cases even higher than that of CA patients. The implementation of standardized diagnostic procedures and interventions to reduce fatigue in RA patients are recommended.
34272096 Overexpression of TLR7 and TLR9 Occurs Before Onset Symptoms In First-Degree Relatives of 2022 Jan BACKGROUND: Autoantibodies have a central role in the physiopathology of Rheumatoid Arthritis (RA). However, the responsible factors that trigger and perpetuate the autoantibodies production are unknown. Toll-like receptors (TLRs) have been considered as promotors of autoantibodies production to break down the immunotolerance in RA. AIM OF THE STUDY: Evaluate the expression levels of TLR7 and TLR9 as well as their correlation with autoantibodies in first-degree relatives (FDR) of RA patients (seropositive and seronegative to ACPA), respect to early RA (eRA) and chronic RA (cRA) patients. METHODS: We selected 32 RA patients (16 as eRA and 16 as cRA) and 32 FDR of RA patients (16 seropositive and 16 seronegative to ACPA). Expression levels of TLR7 and TLR9 in whole blood samples from each group were measured by real-time PCR using total RNA extracted from each subject. Also, correlation analysis between TLRs expression and autoantibodies was performed. RESULTS: The expression of TLR7 and TLR9 was diminished in RA patients (p <0.01) but elevated in ACPA- FDR (p <0.0001) and ACPA+ FDR (p <0.05) with a positive correlation between them (r = 0.749, p <0.000). Moreover, the expression levels of TLR7 correlate positively with ACPA levels in both seropositive ACPA+ FDR subjects (r = 0.582, p = 0.018) and eRA patients (r = 0.593, p = 0.020). CONCLUSIONS: Our results showed overexpression of TLR7 and TLR9 may occur in preclinical RA subjects. TLR7 overexpression correlated with ACPA levels' production, suggesting TLR7 may play a role in ACPA development.
35352909 Adjustment in women treated for rheumatoid arthritis. 2022 Mar 21 INTRODUCTION: The favourable or unfavourable process of a patient's adaptation to a challenging medical condition may indicate that certain adjustment reactions, which can be either constructive or undesirable, tend to prevail. OBJECTIVE: The aim of the study was to examine the adjustment reactions of patients, and to define the correlation between the reactions and socio-demographic factors, health self-assessment, satisfaction with medical care, duration of treatment, and limitations in women treated for rheumatoid arthritis. MATERIAL AND METHODS: The study was conducted at the Department of Rheumatology and Connective Tissue Diseases and the Specialist Outpatient Clinic of the Independent Public Teaching Hospital No. 4 in Lublin, Poland. The Polish adaptation of the Reactions to Impairment and Disability Inventory RIDI (H. Livneh, R. Antonak, 1990) was used in the study, together with an Original Questionnaire. A p-value of <0.05 was set to define statistical differences. Analysis was performed using commercial SPSS Statistics software (IBM Corp., Armonk, NY). RESULTS: Adjustment reactions, adaptive reactions, i.e. adjustment (3±0.5) and acknowledgement (2.6±0.4) were found to markedly prevail, while the lowest mean value was observed for denial (1.9±0.4), which was considered a negative reaction. Longer duration of the disease was associated with a lower level of external hostility. Low health self-assessment and significant limitations impairing everyday activities, caused by pain, deformity and impaired joint mobility, were mostly related to unfavourable early and intermediate non-adaptive reactions. CONCLUSIONS: Knowledge of the adjustment reactions and their moderating factors appears to be crucial in the planning of measures aimed at the rehabilitation of RA patients.
35505266 Early response to JAK inhibitors on central sensitization and pain catastrophizing in pati 2022 Jun OBJECTIVES: To evaluate the effect of 4 weeks of treatment with Janus kinase inhibitors (JAKis) on central sensitization (CS) and pain catastrophizing, and to determine the pain-related variables predictive of disease activity improvement, in patients with active rheumatoid arthritis (RA). METHODS: Consecutive RA patients with active disease starting a JAKi have been enrolled in this prospective observational study. Patients have been assessed at baseline and after 4 weeks of treatment. The evaluation was comprehensive of disease activity [Simplified Disease Activity Index (SDAI) and ultrasonographic (US) score] and of questionnaires aimed at investigating primarily CS [Central Sensitization Inventory (CSI)] and pain catastrophizing [Pain Catastrophizing Scale (PCS)]. Differences (Δ values) between the final and baseline were studied with the t test, Δ values of the variables were correlated with each other using Pearson's test, and predictor variables for improvement in SDAI were also investigated using multivariate regression analysis. RESULTS: A total of 115 patients were evaluated. Overall, all variables demonstrated significant improvement between baseline and final except the US score. In particular, CSI decreased from 36.73 to 32.57 (p < 0.0001), PCS decreased from 32.46 to 28.72 (p = 0.0001). ΔSDAI showed a significant correlation with both ΔPCS and ΔCSI (r = 0.466 and 0.386, respectively, p < 0.0001). ΔPCS was the only variable predictive of an improvement in SDAI (coefficient = 0.500, p = 0.0224). CONCLUSION: JAKis would appear to have a positive effect on pain-related variables, particularly CS and pain catastrophizing, for the genesis of which extra-synovial mechanisms are responsible.
35284067 Correlation between serum methotrexate-polyglutamate 3 (MTX-PG3) level and disease activit 2022 Background: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, characterized by systemic inflammation, joint destruction and disability. Methotrexate (MTX) is used as the primary treatment for RA patients. However, the response to MTX therapy is highly varied and difficult to predict. This study sought to determine the role of MTX by measuring the MTX polyglutamate 3 (MTX-PG3) levels and the disease activity score 28 based on C-reactive protein (DAS28-CRP) of RA patients. Method: A prospective cohort study was conducted at the Rheumatology Polyclinic of Dr. Cipto Mangunkusumo General Hospital. Thirty-four patients with RA were included and followed up to 12 weeks. The RA patients were treated with MTX 10 mg per week and an increased dose of 5 mg per week every month. DAS28-CRP and MTX-PG3 level were assessed at week 8 and 12. Multivariate logistic regression analysis was used to determine the correlation between MTX-PG3 and DAS28-CRP. Result: A total of 34 RA patients were followed and the MTX was well tolerated in which no increase of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and glomerular filtration rate (GFR) were observed. The mean scores of DAS28-CRP decreased following the MTX-treatment: 3.93, 3.22 and 2.82 at week 0, 8 and 12, respectively. In contrast, the median concentration of MTX-PG3 increased from week 8 to week 12 followed by increasing the dose of MTX. Our analysis suggested there was a moderate positive correlation between MTX-PG3 levels and DAS28-CRP score at week 8 and week 12 post-MTX treatment. Conclusion: The level of MTX-PG3 is correlated with DAS28-CRP score suggesting that MTX-PG3 could be used as an indicator to assess the disease activity in RA patients. Nevertheless, a prospective study with a higher number of patients is needed to confirm this finding.