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ID PMID Title PublicationDate abstract
35348759 Impact of Janus Kinase Inhibitors on Antibody Response to 13-Valent Pneumococcal Conjugate 2022 Mar 26 OBJECTIVE: To evaluate the antibody response to 13-valent pneumococcal conjugate vaccine (PCV13) in patients with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKIs). METHODS: Fifty-three patients receiving methotrexate (MTX) (n = 10), JAKI (n = 20), or MTX + JAKI (n = 23) were vaccinated with PCV13. Serum concentrations of IgG antibodies to 13 pneumococcal serotype capsular polysaccharides were quantified before and 4-6 weeks after vaccination. Positive antibody response was defined as a two-fold or more increase in IgG concentrations from pre-vaccination levels. RESULTS: After vaccination, IgG concentrations significantly increased in all treatment groups (p <0.001), but fold increases (post-vaccination to pre-vaccination ratios) were different among treatment groups (9.30 for MTX, 6.36 for JAKI, and 3.46 for combination therapy). Positive antibody response rates were comparable between the MTX group (90%) and the JAKI group (95%), but lower in the MTX + JAKI group (52.2%). In multivariable logistic regression analysis, the combination therapy was the only factor associated with reduced antibody response to PCV13. No severe adverse events were observed in any treatment group. CONCLUSION: Although JAKIs do not impair PCV13 immunogenicity in RA patients, the combination of MTX with JAKI can reduce the antibody response in this patient population.
35234889 Comparable Efficacy of Denosumab and Romosozumab in Patients with Rheumatoid Arthritis Rec 2022 Mar 1 OBJECTIVES: Romosozumab is a newly released and widely known molecular-targeted drug for severe osteoporosis treatment with comparable effectiveness to denosumab. However, there have been no reports discussing the efficacy of those treatments for rheumatoid arthritis (RA) patients, especially those receiving glucocorticoids. This retrospective observational registry study compared the efficacy of 12 month treatment of denosumab and romosozumab in RA patients under the influence of glucocorticoid intake. METHODS: Following propensity score matching, 36 patients each in the denosumab and romosozumab groups were analyzed in this study. Drug effectiveness was evaluated by measuring bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck at baseline, 6 and 12 months as well as alterations in P1NP, TRACP-5b, and simplified disease activity index (SDAI). The occurrence of adverse events and new fractures was also assessed. RESULTS: At 12 months of treatment, BMD at lumbar spine was increased by 7.5% in the denosumab group and 8.7% in the romosozumab group, which were both significantly and comparably elevated over baseline. At total hip and femoral neck, romosozumab tended to exhibit favorable efficacy to increase BMD versus denosumab. Both P1NP and TRACP-5b were significantly lower in the denosumab group as compared with baseline. Conversely in the romosozumab group, P1NP was increased over baseline, while TRACP-5b was decreased. Regarding SDAI alterations, both the romosozumab and denosumab groups exhibited comparable improvements in RA disease activity over time during treatment. Recorded adverse events and new fractures during treatment were few and minor in both groups. CONCLUSIONS: Romosozumab exhibited comparable efficacy to denosumab for increasing BMD even under the influence of glucocorticoids for treating RA. Both drugs may be therefore suitable for managing osteoporosis in patients with RA and glucocorticoid intake.
34775884 The molecular structure and biological functions of RNA methylation, with special emphasis 2022 May Autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic vasculitis are caused by the body's immune response to autoantigens. The pathogenesis of autoimmune diseases is complex. RNA methylation is known to play a key role in disease progression as it regulates almost all aspects of RNA processing, including RNA nuclear export, translation, splicing, and noncoding RNA processing. This review summarizes the mechanisms, molecular structures of RNA methylations and their roles in biological functions. Similar to the roles of RNA methylation in cancers, RNA methylation in RA and SLE involves "writers" that deposit methyl groups to form N6-methyladenosine (m6A) and 5-methylcytosine (m5C), "erasers" that remove these modifications, and "readers" that further affect mRNA splicing, export, translation, and degradation. Recent advances in detection methods have identified N1-methyladenosine (m1A), N6,2-O-dimethyladenosine (m6Am), and 7-methylguanosine (m7G) RNA modifications, and their roles in RA and SLE need to be further studied. The relationship between RNA methylation and other autoimmune diseases has not been reported, and the roles and mechanisms of RNA modifications in these diseases need to be explored in the future.
35633988 Strong Association of Polymorphism in SPRED2 Gene with Disease Susceptibility and Clinical 2022 Apr BACKGROUND: The high heritability of Rheumatoid Arthritis (RA) has been estimated from different studies. Recently, Genome-Wide Association Studies (GWAS) show a large number of Single Nucleotide Polymorphisms (SNPs) loci affecting susceptibility to RA. The rs934734 polymorphism in the SPRED2 gene is one of these loci. Studies have shown that the SPRED2 gene is involved in the regulation of inflammatory response, leukocyte infiltration, and local chemokine production. In the current study, the possible association between SNP rs934734 (intronic variant) in the SPRED2 gene with RA risk in the Iranian population was evaluated. METHODS: One hundred fourteen RA patients and 120 healthy counterparts were recruited in this case-control study to evaluate rs934734 genotypes using the real-time PCR High Resolution Melting method (HRM). RESULTS: Logistic regression analysis demonstrated that GG and AG genotypes compared with AA genotype increase the risk of RA (GG vs. AA; OR=4.61; 95%CI [2.21-9.35]; p<0.001 and AG vs. AA; OR=2.54; 95%CI [1.36-4.76]; p=0.004). Furthermore, subjects with allele G were more frequently affected with RA than subjects with A allele (OR=2.33; 95%CI [1.61-3.38]; p<0.001). Besides, in the patient group, there was a significant correlation between Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP) concentration with rs934734 polymorphism (p<0.05). CONCLUSION: Our findings suggest that rs934734 in SPRED2 strongly underlies RA development and is associated with clinicopathological characteristics of this disease.
35291607 HOTAIR and THRIL Long Non Coding RNAs and Their Target Genes in Rheumatoid Arthritis patie 2022 Jan BACKGROUND: Rheumatoid arthtritis (RA) is a chronic systemic inflammatory autoimmune disease characterized by irreversible joint damage and deformity. The aim of this study is to investigate THRIL and HOTAIR serum expression and their target genes in Egyptian RA patients and to evaluate their relationship to the clinico-pathological data. METHODS: The present study included fifty-two RA patients and fifty-six healthy controls. RA patients were classified according to DAS28 score. All subjects were subjected to full history taking and clinical examination. Quantitative real time PCR was done to estimate the expression levels of serum THRIL and HOTAIR as well as their target genes tumor necrosis factor alpha (TNF-α) and metalloproteinase 2 (MMP-2) were estimated by ELISA techniques. RESULTS: Results revealed that both THRIL and HOTAIR were statistically over expressed in RA patients compared to healthy group with p-value< 0.05. Results showed as well that the target genes for those long-non coding RNAs, TNF-α and MMP-2, were also significantly higher in RA patients compared to healthy controls. CONCLUSION: Both THRIL and HOTAIR associated with their target genes, can be considered as diagnostic markers for RA.
35237610 Gasdermin-E Mediated Pyroptosis-A Novel Mechanism Regulating Migration, Invasion and Relea 2021 Synovium fibroblast-like synoviocytes (FLSs) are important participants in the pathogenesis of synovitis and joint destruction in rheumatoid arthritis (RA). Pyroptosis is a pro-inflammatory and cell lytic programmed cell death mechanism mediated by gasdermin (GSDM) family proteins. In this study, we demonstrated the increased expression of GSDME and increased levels of GSDME-mediated pyroptosis in RA synovial tissues. In vitro, stimulation with TNF-α plus hypoxia mimicking the inflammatory and hypoxic environment in RA synovium induced GSDME-mediated pyroptosis in RA-FLSs in combination with the promotion of migration and invasion abilities and the release of inflammatory cytokines (IL-6, IL-8). Moreover, knockdown of GSDME significantly inhibited the proliferation rate, migration/invasion effects and cytokines released through the reduction of GSDME-mediated pyroptosis. The immunohistochemistry results showed that RA patients with high GSDME N-terminal (GSDME-NT) expression, which is the active form of GSDME, showed higher IL-6 expression in both lining and sublining layer of synovium than that in patients with low GSDME-NT expression, osteoarthritis and non-inflammatory orthopedic arthropathies. Our findings revealed a novel mechanism regulating cell proliferation, migration, invasion and inflammatory cytokines release during the process of GSDME mediated pyroptosis in RA.
35459952 Factors Associated With Frailty in Rheumatoid Arthritis Patients With Decreased Renal Func 2022 Apr 23 OBJECTIVES: To investigate factors associated with frailty in rheumatoid arthritis (RA) patients with decreased renal function. METHODS: RA patients who visited outpatient clinics from June to August 2021 were included (n = 625). Patients with eGFR < 60 ml/min/1.73 m2 were defined as having decreased renal function (n = 221) and divided into the non-frailty (n = 153) and frailty (n = 58) groups. Patient characteristics were compared between the two groups by univariate analysis. Significant factors in univariate analysis were assessed by logistic regression analysis to determine their association with frailty in patients with decreased renal function. RESULTS: Patients in the frailty group were older (74.0 vs.79.0 years) and had a longer duration of disease (11.1 vs. 17.8 years), higher DAS28-ESR (2.99 vs. 3.80), higher HAQ-DI (0.42 vs. 1.43), and a lower rate of MTX use (46.4% vs. 25.9) compared to those in the non-frailty group. Factors associated with frailty in patients with decreased renal function were age (OR: 1.07), duration of disease (1.06), DAS28-ESR (1.85), and MTX use (0.42). CONCLUSIONS: Among factors associated with frailty in RA patients with decreased renal function, improving DAS28-ESR is likely to be the most feasible approach to promote recovery from frailty (200/200 words).
35221707 Association of Growth and Differentiation Factor 15 in Rheumatoid Arthritis. 2022 PURPOSE: Rheumatoid arthritis (RA) is an inflammatory rheumatic disease, which has been demonstrated to correlate with mutated genetics. Growth and differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily and is expressed in different organs, tissues and immune cells. To date, limited studies have evaluated plasma levels of GDF-15 in RA patients, and whether GDF-15 gene polymorphisms correlate with RA risk in the Chinese Han population has not been clarified. PATIENTS AND METHODS: This case-control study recruited 910 age- and sex-matched RA patients and healthy controls. Plasma levels of GDF-15 were examined by enzyme linked immunosorbent assay, and polymorphisms (rs1055150, rs1058587, rs3787023, and rs4808793) were genotyped by KASP method. RESULTS: RA patients had higher levels of GDF-15 as compared to that in healthy controls. Patients with positive CRP also showed higher levels of GDF-15 when compared to that in patients with negative CRP. Levels of GDF-15 correlated with disease activity score. Frequencies of GG, GC, GG+GC genotypes and G allele in GDF-15 gene rs1058587 were significantly elevated in RA patients compared to controls. Frequencies of CC genotype and C allele in GDF-15 gene rs3787023 were higher in RA patients compared to controls. Other polymorphisms did not correlate with RA susceptibility. Moreover, the four polymorphisms were not correlated with levels of GDF-15. CONCLUSION: Plasma levels of GDF-15 were elevated in RA patients and GDF-15 gene polymorphisms were related to RA risk in the Chinese Han population.
35087406 Potential Adverse Events Reported With the Janus Kinase Inhibitors Approved for the Treatm 2021 The aim of this study was to analyze the potential adverse events (AEs) caused by Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, and upadacitinib, used to treat rheumatoid arthritis using spontaneous AE reports from the FDA (FAERS) and interpreting them in correlation with those from Korea (KAERS) and an online patient review (WebMD). Potential AEs were identified based on a disproportionality analysis using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and the information component (IC). A total of 23,720 reports were analyzed from FAERS database, of which 91.5% were reports on tofacitinib. Potentially important medical AEs related to infections were reported frequently, as well as thromboembolism-related AEs. The AEs, such as malignancy, interstitial lung diseases, myocardial infarction, and gastrointestinal disorder, also reported. In an online patient review report, the ineffectiveness of the drug and gastrointestinal AEs were frequently reported. Infection with baricitinib and symptoms related to pain or edema due to upadacitinib were the main discomfort experienced by patients. In conclusion, the results of this study highlight the possible safety issues associated with JAK inhibitors. Routine clinical observations and further research using various real-world databases are needed.
35636524 Discovery and pre-clinical characterization of a selective PI3Kδ inhibitor, LL-00071210 i 2022 May 27 PI3Kδ plays a critical role in adaptive immune cell activation and function. Suppression of PI3Kδ has been shown to counter excessive triggering of immune responses which has led to delineating the role of this isoform in the pathophysiology of autoimmune disorders. In the current study, we have described preclinical characterization of PI3Kδ specific inhibitor LL-00071210 in various rheumatoid arthritis models. LL-00071210 displayed excellent in vitro potency in biochemical and cellular assay against PI3Kδ with IC(50) values of 24.6 nM and 9.4 nM, respectively. LL-00071210 showed higher selectivity over PI3Kγ and PI3Kβ as compared to available PI3K inhibitors. LL-00071210 had good stability in liver microsomes and plasma across species and showed low clearance, low-to-moderate Vss, with bioavailability of >50% in preclinical species. LL-00071210 demonstrated excellent in vivo efficacy in adjuvant-induced and collagen-induced arthritis models. Co-administration of LL-00071210 and methotrexate at subtherapeutic dose regimen in collagen induced arthritis model led to additive effects, indicating the combination potential of LL-00071210 along with available disease modifying anti-rheumatic drugs (DMARD). In conclusion, we have described a specific PI3Kδ inhibitor with ∼100-fold selectivity over other PI3K isoforms. LL-00071210 has good drug-like properties and thus warrants testing in the clinic for the treatment of autoimmune diseases.
35333316 Advanced neural networks for classification of MRI in psoriatic arthritis, seronegative, a 2022 Mar 25 OBJECTIVES: To evaluate whether neural networks can distinguish between seropositive rheumatoid arthritis (RA), seronegative RA and psoriatic arthritis (PsA) based on inflammatory patterns from hand MRI and to test how psoriasis patients with subclinical inflammation fit into such patterns. METHODS: ResNet neural networks were utilized to compare (i) seropositive RA vs. PsA, (ii) seronegative RA vs. PsA and (iii) seropositive vs. seronegative RA with respect to hand MRI data. Results from T1 coronal, T2 coronal, T1 coronal and axial fat suppressed contrast-enhanced (CE) and T2 fat suppressed axial sequences were used. The performance of such trained networks was analyzed by the area-under-the-receiver-operating-characteristic curve (AUROC) with and without presentation of demographic and clinical parameters. Additionally, the trained networks were applied to psoriasis patients without clinical arthritis. RESULTS: MRI scans from 649 patients (135 seronegative RA, 190 seropositive RA, 177 PsA, 147 psoriasis) were fed into ResNet neural networks. AUROC was 75% for seropositive RA vs. PsA, 74% for seronegative RA vs. PsA and 67% for seropositive vs. seronegative RA. All MRI sequences were relevant for classification, however, when deleting contrast agent-based sequences the loss of performance was only marginal. The addition of demographic and clinical data to the networks did not provide significant improvements for classification. Psoriasis patients were mostly assigned to PsA by the neural networks, suggesting that a PsA-like MRI pattern may be present early in the course of psoriatic disease. CONCLUSION: Neural networks can be successfully trained to distinguish MRI inflammation related to seropositive RA, seronegative RA, and PsA.
33667534 Rheumatoid pannus presenting as a large epidural mass in the subaxial cervical spine: A ca 2022 Jan Rheumatoid arthritis (RA) is a debilitating inflammatory condition characterised by joint damage that affects the cervical spine most commonly at the atlantoaxial joint resulting in neck pain and myelopathy. The pathogenesis of RA involves the formation of a hyperplastic synovial tissue, termed pannus, which invades the local bone and causes osseous erosion. Here, we describe a case of rapid onset quadriparesis due to spinal cord compression at C5-C6 secondary to vertebral subluxation and mass effect from a large inflammatory pannus in the subaxial spine. Surgical decompression and resection of the subaxial pannus were performed, and the patient regained strength in all extremities. Histopathologic evaluation of the resected tissue confirmed the diagnosis of pannus over other more common epidural masses. Pannus formation commonly occurs in the peri-odontoid region; however, its presentation as a large soft tissue mass in the subaxial spine is not described in the current literature. Therefore, pannus should be considered in the differential diagnosis of epidural masses in the spine of RA patients. We use this case to discuss the pathology and radiological findings relevant to rheumatoid pannus formation in the subaxial cervical spine, as well as emphasise the importance of treatment in the context to severe degenerative disease.
35342627 Correlation between percentage of fat mass and level of disease activity in rheumatoid art 2022 INTRODUCTION: Controversies exist regarding the relationship between body fat and disease activity in patients with rheumatoid arthritis. The evaluation of the disease is critical for establishing treatment and prognosis. Fat mass could be a predictive factor for poor prognosis in rheumatoid arthritis because of its association with low- and high-grade inflammation. OBJECTIVE: To evaluate the correlation between fat mass values and disease activity in patients with rheumatoid arthritis. MATERIALS AND METHODS: This was a cross-sectional study. Eighty female patients diagnosed with rheumatoid arthritis (American College of Rheumatology of 1987) were evaluated. For each one, the evaluation determined fat mass using bioelectrical impedance analysis and disease activity using the Disease Activity Score on 28 joints (DAS28). RESULTS: The mean age was 59.11 ± 9.92 years, with an average disease duration of 14.13 ± 10.13 years; 85% of patients showed a high body fat percentage. Pearson's correlation between DAS28 values and fat mass was r = 0.035 (p = 0.76). CONCLUSION: The levels of DAS28 showed no correlation with fat mass percentage. Further studies are required to clarify the factors that can modify these levels.
35370836 The Effects of Patient Education on Psychological Status and Clinical Outcomes in Rheumato 2022 BACKGROUND: Rheumatoid arthritis (RA) is a common systemic inflammatory autoimmune disease. The disease has a serious impact on mental health and requires more effective non-pharmacological interventions. OBJECTIVE: This study aims to systematically evaluate the effectiveness of patient education on psychological status and clinical outcomes in rheumatoid arthritis. METHODS: This systematic review and meta-analysis was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Cochrane Library, EMBASE database, and Web of Science database were screened for articles published until November 2, 2021. Randomized controlled trials (RCTs) of patient education for RA were included. Outcomes measures included pain, physical function, disease activity, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anxiety, depression, Arthritis Self-Efficacy (pain, other symptoms, total), and General health. For each outcome, standardized mean differences or mean differences and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 24 RCTs (n = 2,276) were included according to the inclusion and exclusion criteria. Meta-analysis revealed a statistically significant overall effect in favor of patient education for physical function [SMD = -0.52, 95% CI (-0.96, -0.08), I (2) = 93%, P = 0.02], disease activity [SMD = -1.97, 95% CI (-3.24, -0.71), I (2) = 97%, P = 0.002], ASE (pain) [SMD = -1.24, 95% CI (-2.05, -0.43), I (2) = 95%, P = 0.003], ASE (other symptoms) [SMD = -0.25, 95% CI (-0.41, -0.09), I (2) = 25%, P = 0.002], ASE (total) [SMD = -0.67, 95% CI (-1.30, -0.05), I (2) = 90%, P = 0.03], and general health [SMD = -1.11, 95% CI (-1.36, -0.86), I (2) = 96%, P < 0.00001]. No effects were found for anxiety [SMD = 0.17, 95% CI (-0.64, 0.98), I (2) = 82%, P = 0.68], depression [SMD = -0.18, 95% CI (-0.52, 0.15), I (2) = 52%, P = 0.28], pain [SMD = -0.37, 95% CI (-0.80, 0.05), I (2) = 89%, P = 0.08], and CRP [SMD = -0.27, 95% CI (-0.57, 0.02), I (2) = 0%, P = 0.07]. CONCLUSIONS: Patient education may be effective in improving clinical outcomes and psychological status in patients with rheumatoid arthritis. Considering the methodological limitations of the included RCTs, more high-quality and large-sample RCTs are needed to confirm this conclusion in the future. SYSTEMATIC REVIEW REGISTRATION: http://www.crd.york.ac.uk/prospero, identifier: CRD42021250607.
35154127 No Genetic Causal Association Between Periodontitis and Arthritis: A Bidirectional Two-Sam 2022 OBJECTIVES: Periodontitis (PD) has been linked to arthritis in previous epidemiological observational studies; however, the results are inconclusive. It remains unclear whether the association between PD and arthritis is causal. The purpose of this study was to investigate the causal association of PD with arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: We performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy. RESULTS: Genetically determined PD did not have a causal effect on OA (OR = 1.06, 95% CI: 0.99-1.15, P = 0.09) and RA (OR = 0.99, 95% CI: 0.87-1.13, P = 0.89). Furthermore, we did not find a significant causal effect of arthritis on PD in the reverse MR analysis. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates according to the sensitivity analysis. CONCLUSIONS: Our MR analysis reveals non-causal association of PD with arthritis, despite observational studies reporting an association between PD and arthritis.
35224306 The protein corona modulates the inflammation inhibition by cationic nanoparticles via cel 2022 Jul A central paradigm in nanomedicine is that when synthetic nanoparticles (NPs) enter the body, they are immediately cloaked by a corona of macromolecules (mostly proteins) that mediates the role of the physico-chemical properties in the NP biological functions (the "coronation paradigm"). In this work, we focused on the assessment of the "coronation paradigm" for cationic NPs (cNPs) used as rheumatoid arthritis (RA) drugs due to their ability to scavenge cell-free DNA (cfDNA). We fabricated series of cNPs uniformly coated with single or di-hydroxyl groups and different types of amino groups and showed that hydroxylated nanoparticles displayed a prolonged retention in inflamed joints and greater anti-inflammatory effect in collagen-induced arthritis (CIA) rats than the non-hydroxylated analogues. Especially, the cNPs with secondary amines and a di-hydroxyl shell showed the best performance among the tested cNPs. Proteomic analysis showed that the cNPs with a di-hydroxyl shell adsorbed less opsonin proteins than the cNPs carrying mono hydroxyl groups and non-hydroxylated ones, which may provide a mechanistic explanation for the different biodistribution profiles of cNPs. Thus, this study suggests that the protein corona mediates the effects of the surface chemistry on the fate and functions of cNPs as anti-RA drugs.
35221875 Multicentric Carpotarsal Osteolysis Syndrome in a Mother and Daughter with a MAFB Missense 2022 Feb Multicentric carpotarsal osteolysis syndrome (MCTO; MIM #166300) is a rare skeletal disorder characterized by osteolysis affecting particularly the carpal, metacarpal, and tarsal bones, although other bones might be involved. MCTO is an autosomal dominant disease caused by heterozygous variants in the MAFB gene, frequently misdiagnosed as juvenile rheumatoid arthritis due to similar clinical manifestations. This study reports the first Brazilian family diagnosed with MCTO with progressive osteolysis of the carpal and tarsal bones, presenting a c.161C>T (p.Ser54Leu) heterozygous variant in the MAFB gene, describing the clinical, radiological, and molecular findings, compared with literature data, and discussing the different clinical and molecular diagnosis, as well as the natural history of the disease. Since MCTO is a disorder with progressive symptoms, an early diagnosis is important to avoid unnecessary investigations and treatments and to provide the proper follow-up.
34735597 [Still's syndrome-similarities and differences between the juvenile and adult forms]. 2022 Feb Still's syndrome includes systemic juvenile idiopathic arthritis (sJIA) and the adult form of Still's disease (adult-onset Still's disease, AOSD). Except for age, there are many similarities between sJIA and AOSD. A biphasic disease model is currently put forth. At disease onset, autoinflammation predominates, which is caused by dysregulation of the innate immune system. Later on, the disease can progress to a chronic-articular form, which is predominantly mediated by the adaptive immune system and is consequently due to autoimmunity. The "window-of-opportunity" hypothesis is based on this biphasic model and supports the assumption that an early, targeted therapy with cytokine blockade can prevent disease progression to chronic destructive arthritis. Macrophage activation syndrome (MAS) is a serious complication of the so-called cytokine storm during the systemic phase of the disease. Clinically, there are many similarities between sJIA and AOSD. Recurrent fever, a fleeting, salmon-colored rash, and arthralgia/arthritis are common signs and symptoms of both sJIA and AOSD. The few differences are mainly related to the therapies and their side effects in children versus adults. In addition, the contribution of genetics to pathogenesis is more pronounced in sJIA compared to AOSD, but there are also smooth transitions in this respect and both diseases are heavily influenced by exogenous factors such as microbial triggers. Future research aspects could include additional investigation of these triggers such as viruses, bacteria, or dysbiosis of the human microbiome.
35578115 B cell depletion in patients with rheumatoid arthritis is associated with reduced IL-1β i 2022 May 17 OBJECTIVES: We evaluated the effect of B cell depletion on the clinical periodontal findings and IL-1β and MMP-8 levels of the gingival crevicular (GCF) fluid in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: Seventy patients were included in this case-control study. Twenty patients with RA were undergoing B-cell depletion treatment. The second group of RA patients (n = 20) were undergoing non-B-cell depletion treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARD). Control group, with no RA, consisted of 30 individuals. Periodontal parameters including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival index (GI), and plaque index (PI) were recorded. IL-1β and MMP-8 levels in GCF were determined using enzyme-linked immunosorbent assay. Rheumatological parameters including Disease Activity Score-28 (DAS-28), rheumatoid factor levels (RF), and anti-cyclic citrullinated peptide levels were included in the data analyses. RESULTS: All groups were similar in PD, CAL, BOP, GI, and PI measures. GCF IL-1β levels were 1.85 ± 1.67 pg in the B-cell depletion group, 10.50 ± 13.16 pg in the DMARD group, and 34.12 ± 29.45 pg in the control group (p < 0.001). MMP-8 levels were 21.00 ± 4.23 pg in the B-cell depletion group, 8.16 ± 6.94 pg in the DMARD group, and 21.45 ± 8.67 pg in the control group (p < 0.001). DAS 28, RF, and anti-CCP were similar in RA groups. CONCLUSIONS: GCF IL-1β levels were significantly lower in B cell depletion group, and MMP-8 levels were significantly lower in DMARD group, suggesting that rheumatoid arthritis treatments may modify biochemical parameters of GCF. CLINICAL RELEVANCE: This study suggests that host modulation therapies in RA can reduce local production of IL-1β and MMP-8. Reduction of these inflammatory cytokines and enzymes may have a beneficial effect in controlling periodontal tissue destruction.
34719315 Dehydroevodiamine suppresses inflammatory responses in adjuvant-induced arthritis rats and 2022 Jan Dehydroevodiamine (DHE) is an effective natural active substance extracted from Euodiae Fructus, which is a widely used herbal drug in traditional Chinese medicine. The focus of this study was to test the possibility of using DHE in the treatment of rheumatoid arthritis (RA) diseases. A rat model of adjuvant-induced arthritis (AIA) was generated using Complete Freund's Adjuvant (CFA). Body weight changes, arthritis scores, ankle pathology, tumor necrosis factor-alpha (TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) secretion, as well as matrix metalloproteinase (MMP) expression in joint tissue, were measured as indicators of viability of DHE medicated AIA rats. Human fibroblast-like synoviocytes (MH7A cells) were connected to check these impacts. The results confirmed that DHE administration had an excellent therapeutic impact on the AIA rat model, substantially relieving joint swelling, inhibiting synovial pannus hyperplasia, and decreasing joint scores. In addition, the serum enzyme-linked immunosorbent assay (ELISA) showed that DHE treatment reduced the expression of pro-inflammatory factors in AIA rats. The immunohistochemical results showed that DHE treatment could reduce the synthesis of MMPs such as matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-3 (MMP-3) in the ankle tissue of AIA rats. In vitro, DHE inhibited cell proliferation, mRNA transcription, protein synthesis of proinflammatory factors such as IL-1βand IL-6, and matrix metalloproteinases such as MMP-1 and MMP-3. Furthermore, DHE inhibited the phosphorylation levels of p38, JNK, and ERK proteins in TNF-α-treated MH7A cells.This work assessed the effect of DHE in AIA rats and revealed its mechanism in vitro.