Serum Levels Of Rheumatoid Factor Research Articles

Individualized treatment strategy for patients with rheumatoid arthritis based on imaging evaluation

Purpose: To study the effect of individualized treatment strategy based on imaging evaluation in patients with rheumatoid arthritis (RA).
 Methods: Eighty patients with RA of the wrist treated in the Second Affiliated Hospital of Nanjing Medical University, China from January 2018 to December 2022 were assigned to control and study groups. Conventional methods were used for treating control subjects, based on RA laboratory index results, while the study group received individualized treatment based on RA laboratory index results and results of imaging evaluation. Before and after treatment, serum levels of rheumatoid factor (RF) and C-reactive protein (CRP) were assayed using immunoturbidimetry. Erythrocyte sedimentation rate (ESR) was determined by Wei method. Imaging examination - ultrasound or magnetic resonance imaging (MRI) - was carried out in study group before and after treatment. Disease activity score 28 (DAS28) and score on the visual analogue scale (VAS) were evaluated before and after treatment, and the curative effect in the two groups was compared based on curative effect evaluation.
 Results: In both groups, post-treatment values of RF, CRP and ESR were lower than the corresponding pre-treatment levels, but were significantly smaller in study group (p < 0.05). The DAS28 and VAS scores of the two groups after treatment were significantly lower (p < 0.05) than the pretreatment levels, but the DAS28 and VAS scores were significantly lower in study group (p < 0.05). Treatment efficacy in study group (95.0 %) was significantly higher than in control patients (77.5 %, p = 0.0476). The results of imaging indicators showed significantly reduced post-treatment synovial thickness and joint effusion in study group patients when compared with control patients (p < 0.01).
 Conclusion: Individualized treatment strategy for RA patients based on imaging results enhances curative effectiveness, reduces disease activity, relieves pain, and improves the quality of life of patients.

Associations of Rheumatoid Factor, Rheumatoid Arthritis, and Interleukin-6 Inhibitor with the Prognosis of Ischemic Stroke: a Prospective Multicenter Cohort Study and Mendelian Randomization Analysis.

Rheumatoid factor (RF), an established diagnostic biomarker for rheumatoid arthritis (RA), is associated with cardiovascular diseases, but its impact on clinical outcomes of ischemic stroke remains unclear. We aimed to investigate the observational associations between serum RF and prognosis of ischemic stroke, and further examined the genetic associations of RA and its therapeutic strategy, interleukin-6 (IL-6) inhibitor, with prognosis of ischemic stroke. We measured serum RF levels in 3474 Chinese ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score ≥3) at 3 months after stroke onset. Mendelian randomization (MR) analyses were performed to examine the associations of genetically predicted RA and IL-6 inhibition with prognosis of ischemic stroke. During 3 months of follow-up, 866 patients (25.43%) experienced death or major disability. After multivariate adjustment, RF-positive was significantly associated with a high risk of primary outcome (OR, 1.47; 95% CI, 1.08-2.00; P =0.016) compared with RF-negative. The two-sample MR analyses suggested that genetically predicted RA was associated with an increased risk of primary outcome (OR, 1.09; 95% CI, 1.01-1.18; P=0.021), while genetically predicted IL-6 inhibition was associated with a decreased risk of primary outcome (OR, 0.88; 95% CI, 0.77-0.99; P=0.041). We found that positive RF was associated with increased risks of adverse outcomes after atherosclerotic ischemic stroke, and genetically predicted RA and IL-6 inhibition increased and decreased the risks of adverse outcomes after ischemic stroke, respectively.

Post-Covid-19 Immunological Disorder: A Possible Pathological Entity in a 43 Year Old Man

Background: Post-COVID-19 systemic inflammatory syndrome is considered to be an aquired immunological disorder, which may develop in some individuals after the remission of infection with SARS-CoV-2 and defined by inflammatory clinical manifestations (fever, arthralgias, cutaneous and mucosal pallor, physical weakness) and modified biological parametres (normochromic normocytic anaemia, increased serum levels of C reactive protein and rheumatoid factor), with no proof of an infectious process, to which corticotherapy may be a suitable therapeutic strategy. Case Report: A 43 year old male was admited in the Department of Internal Medicine for high fever (39,4°C), moderate polyarthralgias and physical weakness, with a negative test result of SARS-CoV-2 RT-PCR. The patient had been previously diagnosed with a moderate-to-severe form of COVID-19, a month prior to the current admission. The patient also experienced transitory dry cough for a month, with no other relevant clinical abnormalities. Upon physical examination, cutaneous and scleral pallor was observed and lung auscultation revealed hardened vesicular murmur bilaterally. Blood analysis revealed normochromic normocytic anaemia and increased serum levels of rheumatoid factor and of C reactive protein, which suggested a nonspecific inflammatory syndrome. Although blood cultures and other microbiological tests were negative for an infectious process, a chest X-ray was performed, which detected the presence of a nodular formation in the superior left lung lobe. Several differential diagnoses were taken into consideration, including pulmonary sarcoidosis and granulomatosis with polyangiitis, both of which were excluded, clinically and biologically. A thoracic computed tomography (CT) was later performed, which revealed the presence of a tumoral nodule in the left lung, associated with multiple mediastinal and supraclavicular lymphadenopathies, indicative of lung cancer. However, lung cancer was also excluded upon the histopathological examination of paratracheal lymphnodes, which detected multiple areas of parenchymal necrosis surrounded by dense inflammatory infiltrates, formed predominantly by histiocytes. All of these findings resulted in the diagnosis of a post-COVID-19 rheumatoid syndrome, the only therapeutic strategy being the administration of high doses of intravenous and oral methylprednisolone, which improved the patient’s health. Conclusion: Post-COVID-19 immunological disturbances should be taken into consideration in patients who experience repetitive clinical and biological inflammatory manifestations after the remission of the infection with SARS-CoV-2, which may be improved through high dose corticosteroid therapy

Effects of low-level laser therapy and therapeutic ultrasound on Freund's complete adjuvant-induced knee arthritis model in rats.

The aim of this study was to evaluate and monitor the effect of low-level laser therapy (LLLT) and therapeutic ultrasound (TU) alone, or combined with intra-articular prednisolone (P) in Freund's complete adjuvant (FCA)-induced knee arthritis model in rats. A total of 56 adult male Wistar rats were divided into seven groups: control (C), disease control (RA), P, TU, LLLT (L), P + TU (P+TU), P + LLLT (P+L) groups. The skin temperature, radiography, joint volume, serum rheumatoid factor (RF), interleukin (IL)-1β, serum tumor necrosis factor-alpha (TNF-α), and histopathological evaluation of joint were performed. Thermal imaging and radiographic examination provided results consistent with the severity of the disease. The mean joint temperature (°C) was the highest in the RA (36.2±1.6) group on Day 28. The P+TU and P+L groups significantly decreased radiological scores at the end of the study. The rat serum TNF-α, IL-1β, and RF levels in all groups were significantly higher compared to the C group (p<0.05). Compared to the RA group, serum TNF-α, IL-1β, and RF levels were significantly lower in the treatment groups (p<0.05). The P+TU and P+L group was showed minimal chondrocyte degeneration and cartilage erosion and mild cartilage fibrillation and mononuclear cell infiltration of synovial membrane compared to the P, TU, and L group. The LLLT and TU effectively reduced inflammation. In addition, a more effective result was obtained from the use of LLLT and TU combined with intra-articular P. This result may be due to insufficient dose of LLLT and TU, thus further studies should be focus on at higher dose ranges on FCA arthritis model in rats.

Post-Covid-19 Immunological Disorder: A Possible Pathological Entity in a 43 Year Old Man

Abstract Background. Post-COVID-19 systemic inflammatory syndrome is considered to be an aquired immunological disorder, which may develop in some individuals after the remission of infection with SARS-CoV-2 and defined by inflammatory clinical manifestations (fever, arthralgias, cutaneous and mucosal pallor, physical weakness) and modified biological parametres (normochromic normocytic anaemia, increased serum levels of C reactive protein and rheumatoid factor), with no proof of an infectious process, to which corticotherapy may be a suitable therapeutic strategy. Case report. A 43 year old male was admited in the Department of Internal Medicine for high fever (39,4°C), moderate polyarthralgias and physical weakness, with a negative test result of SARS-CoV-2 RT-PCR. The patient had been previously diagnosed with a moderate-to-severe form of COVID-19, a month prior to the current admission. The patient also experienced transitory dry cough for a month, with no other relevant clinical abnormalities. Upon physical examination, cutaneous and scleral pallor was observed and lung auscultation revealed hardened vesicular murmur bilaterally. Blood analysis revealed normochromic normocytic anaemia and increased serum levels of rheumatoid factor and of C reactive protein, which suggested a nonspecific inflammatory syndrome. Although blood cultures and other microbiological tests were negative for an infectious process, a chest X-ray was performed, which detected the presence of a nodular formation in the superior left lung lobe. Several differential diagnoses were taken into consideration, including pulmonary sarcoidosis and granulomatosis with polyangiitis, both of which were excluded, clinically and biologically. A thoracic computed tomography (CT) was later performed, which revealed the presence of a tumoral nodule in the left lung, associated with multiple mediastinal and supraclavicular lymphadenopathies, indicative of lung cancer. However, lung cancer was also excluded upon the histopathological examination of paratracheal lymphnodes, which detected multiple areas of parenchymal necrosis surrounded by dense inflammatory infiltrates, formed predominantly by histiocytes. All of these findings resulted in the diagnosis of a post-COVID-19 rheumatoid syndrome, the only therapeutic strategy being the administration of high doses of intravenous and oral methylprednisolone, which improved the patient’s health. Conclusion. Post-COVID-19 immunological disturbances should be taken into consideration in patients who experience repetitive clinical and biological inflammatory manifestations after the remission of the infection with SARS-CoV-2, which may be improved through high dose corticosteroid therapy.

Serum rheumatoid factor IgA, anti-citrullinated peptide antibodies with secretory components, and anti-carbamylated protein antibodies associate with interstitial lung disease in rheumatoid arthritis

ObjectiveRheumatoid arthritis (RA) is often complicated with chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway disease, which occur as extra-articular manifestations. CLD in RA have been associated with the production of rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), or anti-carbamylated protein (CarP) antibody. However, few validation studies have been performed thus far. In the present study, we investigated the association of RF, ACPA, and anti-CarP antibodies with RA complicated with CLD.MethodsSera from RA patients with or without CLD were collected. The levels of serum RF, RF immunoglobulin A (IgA), ACPA IgG, ACPA IgA, and ACPA secretory component (SC) were measured using enzyme-linked immunosorbent assay.ResultsThe comparison of RA patients with and without CLD showed that RF IgA was associated with ILD (mean ± standard deviation: 206.6 ± 400.5 vs. 95.0 ± 523.1 U/ml, respectively, P = 1.13 × 10− 8), particularly usual interstitial pneumonia (UIP) (263.5 ± 502.0 U/ml, P = 1.00 × 10− 7). ACPA SC was associated with RA complicated with ILD (mean ± standard deviation: 8.6 ± 25.1 vs. 2.3 ± 3.4 U/ml, respectively, P = 0.0003), particularly nonspecific interstitial pneumonia (NSIP) (10.7 ± 31.5 U/ml, P = 0.0017). Anti-CarP antibodies were associated with RA complicated with ILD (0.042 ± 0.285 vs. 0.003 ± 0.011 U/ml, respectively, P = 1.04X10− 11).ConclusionRF IgA and ACPA SC in RA were associated with UIP and NSIP, respectively, suggesting different specificities in patients with RA. Anti-CarP antibodies were associated with ILD in RA. These results may help elucidate the different pathogeneses of UIP and NSIP in RA.

Dose-dependent effects of oleuropein administration on regulatory T-cells in patients with rheumatoid arthritis: An in vitro approach.

Introduction:Rheumatoid arthritis (RA) is an autoimmune disease that is identified with chronic inflammation and progressive destruction of the joints. The defective activity of regulatory T cells (Tregs) plays a crucial role in RA development. Oleuropein (OLEU) is the most common polyphenolic compound in olive leaf extracts with numerous pharmacological activities. In this study, the potential effects of OLEU in shifting CD4+ T cells toward Tregs are evaluated in patients with RA.Methods32 healthy controls (HC) and 45 RA patients were included in two groups. The immunoturbidometric technique was used to measure serum levels of c-reactive protein (CRP) and rheumatoid factor (RF). Isolated CD4+ T cells from peripheral blood mononuclear cells (PBMCs) of HC and RA patients were cultured with appropriate concentrations of OLEU. The cytotoxicity effects of OLEU were determined using the MTT assay at 24, 48, and 72 h. The percentage of CD4+CD25 + FoxP3 regulatory T lymphocytes (Tregs) and the expressions of IL-10 and TGF-β were evaluated by flow cytometry and immunoassay techniques after treatment of cells with different concentrations of OLEU for 24 h. The serum levels of RF and CRP in patients with RA were 11.8 ± 5.32 IU/ml and 6.36 ± 5.82 mg/l, respectively.ResultsOLEU had a dose-dependent effect on the CD4+ T cells via increasing the frequency of CD4+CD25 + FoxP3 Tregs (p = 0.0001). Moreover, it induced the production of IL-10 (p = 0.0001) and TGF-β (p < 0.01) in both HC and RA patients.ConclusionThe findings of this study suggest that OLEU may have immunomodulatory effects by inducing Tregs, and it might help in developing a novel nutrition strategy for management of autoimmune diseases such as RA.

The relationship between serum rheumatoid factor level and SYNTAX score I in patients with acute myocardial infarction.

Rheumatoid factor (RF) has been associated with an increased likelihood of developing coronary artery disease and cardiovascular mortality. This study aimed to evaluate the relationship between serum RF levels and SYNTAX score I (SSI) in patients with acute myocardial infarction. This study included 418 consecutive patients who were diagnosed with acute myocardial infarction and underwent coronary angiography. The baseline serum RF levels of all patients were measured. The study population was divided into 2 groups, namely, ST-segment elevation myocardial infarction (STEMI) group (218 patients) and non-ST-segment elevation myocardial infarction (NSTEMI) group (200 patients). Each group was further divided into 2 subgroups, namely, SSI ≤22 group and SSI >22 group. In the STEMI group, RF levels were significantly higher in the SSI >22 group than that in the SSI ≤22 group (13.0 IU/mL [7.0-51.0 IU/mL] versus 11.0 IU/mL [4.0-37.0 IU/mL], respectively, p=0.002). In the NSTEMI group, RF levels were significantly higher in the SSI >22 group than that in the SSI ≤22 group (15.5 IU/mL [8.0-69.5 IU/mL] versus 13.0 IU/mL [4.0-36.0 IU/mL, respectively], p<0.001). Forward conditional logistic regression analysis demonstrated that neutrophil-to-lymphocyte ratio, total cholesterol level, positive RF, and left ventricular ejection fraction were independently associated with intermediate and high SSI in patients with STEMI. Furthermore, cardiac troponin T levels and positive RF were independently associated with intermediate and high SSI in patients with NSTEMI. Serum RF concentrations are independently associated with SSI in patients with acute myocardial infarction.

Different protective efficacies of a novel antigen-specific DNA vaccine encoding chicken type Ⅱ collagen via intramuscular, subcutaneous, and intravenous vaccination against experimental rheumatoid arthritis

Tolerizing DNA vaccines encoding key autoantigens are one of emerging strategies for the treatment of rheumatoid arthritis (RA). Among these vaccines, the most representative is pcDNA-CCOL2A1, an antigen-specific DNA vaccine encoding chicken type Ⅱ collagen (CCⅡ) with significant therapeutic and prophylactic efficacy in collagen-induced arthritis (CIA) rat models. We compared the in situ expression levels of CCOL2A1-mRNA and CCⅡ protein and the protective efficacies against CIA after a single dose (300 μg/kg) of this vaccine via intramuscular (IM), subcutaneous (SC) and intravenous (IV) vaccinations. The IM vaccination routes resulted in good protective efficacies in terms of decreasing CIA incidence and severity and significantly improved radiographic and histopathologic findings and scores of joints. Furthermore, IM, SC, and IV vaccinations markedly decreased serum levels of anti-type Ⅱ collagen (CⅡ) IgG antibodies, but only IM vaccination significantly reduced serum levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody. The vaccine exhibited a continuous CCOL2A1-mRNA expression in the tail and abdominal subcutaneous tissue injection sites, but no CCOL2A1-mRNA signal was observed in muscle. Strikingly, CCⅡ protein expression levels at the three injection sites were comparable with minimal variation. IM administration may be considered the preferred route for RA treatment in clinical practice.

Serum rheumatoid factor is associated with adverse clinical outcomes among ischemic stroke patients

Background and Aims: Rheumatoid factor (RF) has been implicated in the occurrence and development of cardiovascular disease. We aimed to examine the correlation between serum RF levels and prognosis of ischemic stroke.

Corticosteroid injections in the temporomandibular joint temporarily alleviate pain and improve function in rheumatoid arthritis

ObjectivesTo evaluate the effect of corticosteroid injections in the painful temporomandibular joint (TMJ) of patients with rheumatoid arthritis (RA) in relation to systemic inflammatory activity.MethodExamination of 35 patients (median age 54 years; 89% female) included maximum mouth opening capacity, degree of anterior open bite (AOB), TMJ pain intensity at rest, and crepitus. Serum levels of rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serotonin, and plasma levels of interleukine-1β (IL-1β) were determined. Out of the 70 examined joints, 53 joints received a corticosteroid (methylprednisolone) injection after the clinical examination at baseline (T0). The examination was repeated for all patients at T1 (median 3.1 weeks after T0), and for 21 patients at T2 (median 6.3 weeks after T1), of whom 20 patients received a second injection at T1.ResultsMaximum mouth opening capacity significantly increased, and TMJ pain intensity significantly decreased between T0 and T1, but these improvements were no longer present at T2. No differences were found in AOB between the time points. Of the joints that received an injection at T0, 19 joints had pretreatment crepitus, which resolved in eight joints at T1. No correlations were found between the change in mouth opening capacity or TMJ pain intensity and ESR, CRP, serotonin, or IL-1β.ConclusionsMethylprednisolone injections in the TMJ alleviate pain and improve mouth opening capacity for approximately 3 weeks, allowing patients to perform jaw exercises during this timeframe of temporary relief. It thus seems useful for the short-term management of TMJ involvement in RA.Key Points• In rheumatoid arthritis, corticosteroid injection in the temporomandibular joint alleviates pain and improves function.• The clinical improvement achieved with methylprednisolone injections lasts for approximately 3 weeks.• Corticosteroid injections could be used to facilitate and support additional noninvasive, conservative treatment options.

The Effect of Chinese Medicine Compound in the Treatment of Rheumatoid Arthritis on the Level of Rheumatoid Factor and Anti-Cyclic Citrullinated Peptide Antibodies: A Systematic Review and Meta-Analysis.

Objectives: To evaluate the current evidence whether Chinese medicine compound (CMC) can reduce the serum levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP). Methods: We comprehensively searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), the Database for Chinese Technical Periodicals (VIP), and Wanfang data. We then performed a systematic review and meta-analysis of all randomized controlled trials (RCTs) assessing the CMC therapy methods. This study is registered with PROSPERO, number CRD42020216284. Results: In total, 65 studies were eligible for inclusion, including 6099 patients. The result of the meta-analysis showed that compared with common Western medicine therapy, CMC monotherapy or combined with Western medicine was able to reduce serum RF (SMD= −0.85, 95%CI −1.04 to −0.67) and anti-CCP (SMD= −0.56, 95%CI −0.79 to −0.32) levels to some extent. In the efficacy meta-analysis, a greater number of CMC-treated patients achieved the efficacy criteria after a period of treatment, where the relative risk (RR) was 1.20 [1.08, 1.33] for achieving ACR20, 1.57 [1.38, 1.78] for ACR50, and 2.21 [1.72, 2.84] for ACR70. At the same time, there was a statistically significant difference in the effective rate of the patient's TCM symptoms (RR = 1.22, 95%CI 1.19–1.26). Conclusions: Through this meta-analysis and systematic review, we found that CMC for the treatment of RA is effective in reducing RF and anti-CCP levels and might have better clinical efficacy than Western medicine monotherapy. Some active components are responsible for this efficacy and worth further exploring.

Phytochemical and In-Vivo Anti-Arthritic Significance of Aloe thraskii Baker in Combined Therapy with Methotrexate in Adjuvant-Induced Arthritis in Rats.

Unlike other widely known Aloe species used for treatment of rheumatoid arthritis, this species suffers from a lack of sufficient studies on its biological and chemical characters. This is what drove us to perform this work to evaluate the in vivo anti-arthritic potential of its leaf ethanolic extract. The in vivo anti-arthritic activity of the leaf ethanolic extract at 100 and 200 mg/kg/day b.wt. was evaluated alone and in combination with methotrexate (MTX) using complete Freund’s adjuvant. Serum levels of rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP), cytokines pro-inflammatory marker, inflammatory mediator serum levels, and oxidative stress mediators were analyzed, in addition to liver function. Orientin, isoorientin, β-sitosterol, its palmitate and its glucoside were isolated. The combined therapy of MTX and the leaf ethanolic extract (especially at 200 mg/kg b.wt.) group showed better activity compared to MTX alone. Moreover, the combined therapy provided additional benefits in lowering the liver toxicity by comparison to MTX alone. We concluded that a synergetic combination of the leaf ethanolic extract and MTX is beneficial in the management of rheumatoid arthritis with fewer side effects on liver function, as well as the possibility of the leaf extract to stand alone as an effective natural anti-arthritic agent.

Thoracic Manifestations of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is one of the most common chronic systemic inflammatory diseases and the most common chronic inflammatory arthritis. Classically a progressive symmetric polyarthritis, RA is characterized by inflammation, erosions, bone loss, and joint destruction. Up to half of patients with RA exhibit extra-articular manifestations (EAMs), which may precede articular disease and are more common in patients with seropositive RA (patients with detectable serum levels of rheumatoid factor and/or anticitrullinated peptide antibodies). Cardiovascular and pulmonary EAMs are the largest contributors to morbidity and mortality in RA and may be especially devastating. Imaging has a significant role in diagnosing these EAMs and assessing response to treatment. Although treatment with disease-modifying antirheumatic drugs has redefined the natural history of RA and helped many patients achieve low disease activity, patients are at risk for treatment-related complications, as well as infections. The clinical features of drug-induced lung disease and infection can overlap considerably with those of EAMs, presenting a diagnostic challenge. Radiologists, by recognizing the imaging characteristics and evolution of these various processes, are essential in diagnosing and distinguishing among EAMs, treatment-related complications, and unrelated processes and formulating an appropriate differential diagnosis. Moreover, recognizing these disease processes at imaging and contextualizing imaging findings with clinical information and laboratory and pathologic findings can facilitate definitive diagnosis and proper treatment. The authors review the articular and extra-articular thoracic imaging manifestations of RA, including cardiovascular, respiratory, and pleural diseases, as well as treatment-related complications and common infections. ©RSNA, 2021.

Aliskiren, tadalafil, and cinnamaldehyde alleviate joint destruction biomarkers; MMP-3 and RANKL; in complete Freund's adjuvant arthritis model: Downregulation of IL-6/JAK2/STAT3 signaling pathway

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, which is accompanied by progressive joint damage and disability. The intolerability of conventional antirheumatic drugs by some patients necessitates the search for effective antirheumatic agents having better tolerability. In the current work, we aimed to investigate the efficacy of cinnamaldehyde, tadalafil, and aliskiren as potential antirheumatic candidates and to explore their modulatory effects on joint destruction, inflammatory response, and intracellular signaling. Arthritis was induced in female Wistar rats by complete Freund's adjuvant (CFA) 0.4 ml s.c. on days 1, 4, and 7. Treated groups received their respective drugs, starting from day 13, daily for 3 weeks. Methotrexate and prednisolone were the standard antirheumatic drugs, while cinnamaldehyde, tadalafil, and aliskiren were the test agents. Treatment with cinnamaldehyde, tadalafil, or aliskiren reduced serum levels of rheumatoid factor, and pro-inflammatory cytokines; tumor necrosis factor-alpha and interleukin-6 (IL-6), along with elevated level of IL-10 which is an anti-inflammatory cytokine. Besides, cartilage and bone destruction biomarkers; matrix metalloproteinase-3 (MMP-3) and receptor activator of nuclear factor-kappa B ligand (RANKL); were significantly reduced after treatment with the test agents, which was further confirmed by histopathological investigation. The elevated protein expressions of phosphorylated-Janus kinase 2 (p-JAK2), phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), and inducible nitric oxide synthase (iNOS) in articular tissue were markedly attenuated after treatment with cinnamaldehyde, tadalafil, or aliskiren, while that of endothelial nitric oxide synthase (eNOS) was greatly enhanced. In addition, oxidative stress and inflammatory markers such as malondialdehyde, nitric oxide, and myeloperoxidase were reduced in joint tissue after treatment with the test agents, while glutathione content was elevated. Furthermore, the renin inhibitor aliskiren produced effects close to those of the normal and methotrexate, the gold standard antirheumatic drug, in most of the measured parameters.Collectively, these findings led to the assumption that the downregulation of IL-6/JAK2/STAT3 signaling by cinnamaldehyde, tadalafil, and aliskiren could alleviate joint destruction by MMP-3 and RANKL, reduce iNOS, and enhance eNOS expressions. Moreover, aliskiren could be a promising therapeutic agent for RA, because of its ability to normalize most of the measured parameters after CFA-induced arthritis.

Diagnostic Value of Musculoskeletal Ultrasound in Rheumatoid Finger Arthritis.

To determine the value of musculoskeletal ultrasound (MSUS) in evaluating the pathological features and inflammatory lesions of rheumatoid finger arthritis. A comparative study. Ningbo No. 6 Hospital, China, from September 2017 to February 2020. Eighty patients with rheumatoid finger arthritis (570 finger joints) were examined by MSUS and MRI. Detection rates of the two methods for diagnosing the pathological features of rheumatoid arthritis, levels of the serum markers rheumatoid factor (RF), etc, were compared. Detection rate of joint effusion by MSUS was higher than MRI (p <0.001). Spearman's correlation analysis showed that synovial blood flow signal grade was positively correlated with serum RF, anti-CCP, ESR, CRP, IL-6, and IL-33 levels (r = 0.853, p <0.001; r = 0.864, p <0.001; r = 0.866, p <0.001; r = 0.846, p <0.001; r = 0.881, p <0.001; and r = 0.873, p <0.001, respectively). Resistive index value of intra-synovial artery in active patients was lower than in define inactive patients (p <0.001). Compared to MRI, MSUS has a higher detection rate of joint effusion in RA patients. In the MSUS examination, synovial blood flow signal is positively correlated with RF, Anti-CCP, ESR, CRP, IL-6, and IL-33, and the resistive index of intra-synovial artery is closely related to disease activity. Key Words: Musculoskeletal ultrasound (MSUS), Rheumatoid arthritis (RA), Synovial hyperplasia, Synovial blood flow signal, Serum markers.

Elevated Expression of the Long Noncoding RNA IFNG-AS1 in the Peripheral Blood from Patients with Rheumatoid Arthritis.

Long noncoding RNAs (lncRNAs) have been increasingly recognized as key immune molecules that participate in the pathogenesis of autoimmune diseases. Previous studies have demonstrated that the lncRNA Ifng-AS1, a key scaffold that contributes to the transcription of IFN-γ, depends on T-bet for active transcription in Th1 cells. However, the effect of its human ortholog, IFNG-AS1, on the pathogenesis of rheumatoid arthritis (RA) remains unclear. In this study, we found that the transcript level of lncRNA IFNG-AS1 was increased in the peripheral blood of RA patients. IFNG, as a target gene of IFNG-AS1, was overexpressed and positively correlated with the transcript level of IFNG-AS1 in the RA patients. Our data also showed that the transcript level of T-bet was upregulated and positively correlated with IFNG-AS1 expression. T-bet regulated the transcription of IFNG-AS1 in human CD4+ T cells in vitro. Furthermore, strong positive correlations were observed between the increased transcript level of IFNG-AS1 and the serum level of rheumatoid factor, the erythrocyte sedimentation rate, and the C-reactive protein in RA patients, and patients positive for anticyclic citrullinated peptide antibodies had increased levels of IFNG-AS1. Finally, receiver operating characteristic (ROC) curve analysis suggested that IFNG-AS1 might be a potential biomarker of RA. Taken together, our findings indicated that IFNG-AS1, guided by T-bet, is augmented in the peripheral blood of RA patients and may play a critical role in the pathogenesis of RA by regulating the expression of IFNG.

Relationship between Helicobacter pylori cytotoxin-associated gene A protein with clinical outcomes in patients with rheumatoid arthritis

IntroductionThe Helicobacter pylori(H. pylori) infection leads to intensification of symptoms and calenture of autoimmune diseases. This study aimed to evaluate the relationship between H. pylori infection and clinical outcomes in rheumatoid arthritis (RA) patients. MethodologyThis study was performed on 100 RA patients. Blood samples were collected for measuring Anti-H. pylori IgG antibodies and cytotoxin-associated gene A (CagA) protein. Fresh fecal samples were also collected and the fecal H. pylori antigen was extracted. Clinical condition as well as severity and type of RA symptoms in both groups of H. pylori positive and H. pylori negative were also compared. ResultsSerum levels of rheumatoid factor (RF), ESR, CRP, anti-cyclic citrullinated peptide (Anti−CCP), and anti-mutated citrullinated vimentin (Anti-MCV) were significantly higher in H. pylori positive patients than in H. pylori negative patients (P < 0.05). Serum RF, ESR, CRP and Anti-MCV levels were significantly higher in CagA positive patients than in CagA negative patients (P < 0.05). There were no significant differences in DAS-28 scores between H. pylori positive and H. pylori negative patients (P = 0.064) as well as between patients with positive and negative fecal H. pylori antigen (P = 0.237). However, DAS-28 score was significantly higher in CagA positive patients than in CagA negative patients (P < 0.001). Furthermore, mean VAS score was significantly higher in H. pylori positive patients (P = 0.031) and CagA positive patients (P = 0.004); however, there were no significant differences in VAS scores between patients with positive and negative fecal H. pylori antigen (P = 0.310). ConclusionFollow-up and examination of RA patients in terms of infection with serum and fecal H. pylori organism and CagA seems necessary that will contribute to better and further control and treatment of the patients.

Effect of Tripterygium glycosides combined with Recombinant human tumor necrosis factor receptor II antibody fusion protein for injection on serum vascular endothelial growth factor, rheumatoid factor, receptor activator of nuclear factor κ B ligand levels in patients with rheumatoid arthritis

Objective To investigate the effect of tripterygium glycosides combined with recombinant human tumor necrosis factor receptor Ⅱ antibody fusion protein for injection on serum vascular endothelial growth factor(VEGF), rheumatoid factor(RF), receptor activator of nuclear factor κ B ligand(RANKL) levels in patients with rheumatoid arthritis.To provide reference for rational clinical application. Methods From December 2014 to January 2016, 132 patients with rheumatoid arthritis were divided into observation group and control group by random number table method, , with 66 cases in each group, The control group was treated with tripterygium glycosides alone (10 mg each time, 3 times daily, orally) for 3 months.The observation group was treated with a combination of tripterygium glycosides and recombinant human tumor necrosis factor receptor Ⅱ (0.4 mg/kg, once weekly, hypodermic injection)for 3 months.The clinical efficacy, and serum VEGF, RF and RANKL levels were compared between 2 groups. Results The effective rate of the observation group was 92.4% (61/66), which was significantly higher than that in the control group (80.3%, 53/66). There was a significant difference between the two groups (χ2=4.117, P 0.05). After treatment, the levels of serum VEGF, RF and RANKL in the observation group and the control group were (20.8±11.5) ng/L and (27.3±13.1)ng/L, (258.4±54.5)U/L and (298.1±49.5)U/L, (0.083±0.021) pmol/L and (0.197±0.064), respectively.There were significant differences between the two groups (t=3.029, 4.381, 13.750, all P<0.05). The incidence rate of adverse reactions in the control group was 10.5% (7/66), which was significantly higher than that in the observation group (1.5%, 1/66). There was a significant difference between the two groups(χ2=4.790, P<0.05). The one-year recurrence rate was 25.0% (13/52) in the control group and that was 6.7% (4/60) in the observation group, respectively, and there was a significant difference between the two groups(χ2=7.272, P<0.05). Conclusion Tripterygium glycosidescombined with recombinant human tumor necrosis factor receptor Ⅱ antibody fusion protein for injection is effective in the treatment of rheumatoid arthritis, which reduces the levels of serum VEGF, RF and RANKL, and has a low incidence of adverse reactions and recurrence. Key words: Tripterygium glycosides; Recombinant human tumor necrosis factor receptor Ⅱ antibody fusion protein for injection; Rheumatoid arthritis; Vascular endothelial growth factor; Rheumatoid factor; Receptor activator of nuclear factor κB ligand

Serum Rheumatoid Factor Levels at Acute Phase of Ischemic Stroke are Associated with Poststroke Cognitive Impairment

Background: The effect of serum rheumatoid factor (RF) on poststroke cognitive impairment remains unknown. We aimed to investigate the association of serum RF in the acute phase with cognitive impairment at 3 months after ischemic stroke onset. Methods: Our study was based on a random sample from the China Antihypertensive Trial in Acute Ischemic Stroke, a total of 582 patients from 7 of 26 participating sites of the trial with serum RF levels were included in this analysis. Cognitive impairment was defined as Mini-Mental State Examination less than 27 or Montreal Cognitive Assessment less than 25. Results: According to Mini-Mental State Examination score, the multivariate-adjusted odds ratio and 95% confidence interval of cognitive impairment for the highest tertile of serum RF was 1.79 (1.08-2.99) compared with the lowest tertile. Each standard deviation increase of log-transformed RF was associated with 33% (95% confidence interval: 7%-66%) increased risk of cognitive impairment, and a linear association between serum RF and risk of poststroke cognitive impairment was observed (P for linearity < .01). Adding log-transformed RF to a model containing conventional risk factors improved the predictive power for poststroke cognitive impairment (net reclassification improvement: 26.21%, P < .01; integrated discrimination index: 1.24%, P = .02). Similar significant findings were observed when cognitive function was defined by Montreal Cognitive Assessment score. Conclusions: Elevated serum RF levels in the acute phase were independently associated with 3-month cognitive impairment among ischemic stroke patients. Further studies are needed to replicate our findings and to clarify the potential mechanisms.