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ID PMID Title PublicationDate abstract
35053028 Repeatability and Reliability of the Rheumatoid Arthritis Foot Disease Activity Index in S 2021 Dec 26 Background: The Rheumatoid Arthritis Foot Disease Activity Index (RADAI-F5) questionnaire, based on five questions, is used to assess the severity of rheumatoid arthritis disease in the foot. Nowadays, RADAI-F5 has been validated in different languages; however a Spanish version was lacking. Therefore, the purpose of this research was to translate and validate the Spanish version (RADAI-F5-es). Methods: A cross-cultural translation of the RADAI-F5 questionnaire was performed from English to Spanish. To validate its use, 50 subjects with rheumatoid arthritis who responded to the translated questionnaire two times in an interval of less than 3 months were selected in order to verify the psychometric properties. Results: Excellent agreement between the two versions according to the Cronbach's α was shown. Five domains with regards to arthritis activity in foot joint tenderness and swelling, foot arthritis pain, general foot health and joint stiffness were added together to obtain the total score. Excellent retest reliability was shown for the total score. Test/retest reliability was excellent for joint stiffness on awakening and foot arthritis pain domains. There were no significant differences among any domains (p > 0.05). There were no statistically significant differences (p = 0.000) for the mean ± standard deviations (SD) between pre- and post-tests (98.09 ± 15.42) [93.75-102.43] and 97.96 ± 13.88 [94.5-101.86] points, respectively). Bland-Altman plots or clinically pertinent variations were not statistically significantly different. Conclusions: The RADAI-F5-es is considered a valid and strong tool with adequate repeatability in the Spanish community.
34668328 Trajectory mapping of primary Sjögren's syndrome via transcriptome learning demonstrates 2021 Dec Primary Sjögren's syndrome (pSS) is a complex autoimmune disease characterized by aberrant immune cell action against secretory glands throughout the body. A number of studies have previously identified unique characteristics in the circulating expression profile of white blood cells of pSS patients. However, the molecular progression pattern of pSS is unclear. Through a systematic analysis of pSS transcriptome information, we found that pSS transcriptomes display broad heterogeneity, but cannot be distinguished from the broad range of possible profiles of healthy controls. Instead, only sample learning using a subset of pre-identified signature genes could achieve partial separation through a trajectory governed by interferon activity. Interestingly, this trajectory is correlated with a decrease in dendritic cell counts. Our study thus highlights a major limitation to the utility of broad blood transcriptome analysis in the context of pSS, while also identifying several factors that influence the divergence between patient samples.
34596030 The performance of the diagnostic scoring system or criteria for macrophage activation syn 2021 Sep OBJECTIVES: To evaluate the performance of the diagnostic scoring system/criteria for macrophage activation syndrome (MAS) used in systemic juvenile idiopathic arthritis (sJIA) for adult-onset Still's disease (AOSD). METHODS: This retrospective case-control study included AOSD patients with and without MAS from six hospitals in China. The cut-off values that best discriminated MAS from active AOSD were determined by receiver operating characteristic (ROC) curve analysis. The performance of the present diagnostic scoring system/criteria for sJIA-MAS was evaluated in AOSD-associated MAS. The optimal critical value of the ROC curve replaces the relevant indicators of the existing scoring system and different models were tested for sensitivity/specificity. RESULTS: A total of 56 AOSD-associated MAS patients (AOSD-MAS) and 112 AOSD patients without MAS matched with age and sex treated at six centres between 2007 and 2017 were enrolled. The 2016 MAS in sJIA classification criteria had an overall sensitivity of 100.0% and specificity of 80.4% for classifying AOSD-MAS. Excluding hypertriglyceridemia and substituting some other criteria with newly obtained cut-off values could increase specificity. An MS score ≥-2.1 yielded a sensitivity of 95.2% and a specificity of 76.6% in classifying AOSD-MAS. ROC curve analysis revealed that a score of -1.74 could best discriminate AOSD-MAS from AOSD without MAS. An MS score ≥-1.74 yielded a sensitivity of 93.5% and a specificity of 92.6% in diagnosing AOSD-MAS (AUC=0.96, 95%CI: 0.93-0.99, p<0.0001). CONCLUSIONS: The diagnostic tool for MAS in sJIA with modification appears to apply to AOSD-MAS.
33484384 Topical cyclosporine a (0.05%) treatment in dry eye patients: a comparison study of Sjogre 2021 Apr PURPOSE: To evaluate the clinical effect of topical cyclosporine A (CsA) (0.05%) on dry eye patients with Sjogren's syndrome (SS) and non-Sjogren's syndrome (NSS). METHOD: This retrospective comparative study includes the dry eye (DE) patients who were treated with topical CsA. DE patients were divided into two groups as follows: DE with Sjogren's syndrome (DE-SS) and DE with Non-Sjogren's syndrome (DE-NSS). Dry eye parameters were recorded at baseline and each visit. RESULTS: Schirmer's test 1 scores were 2.7 ± 0.5 mm at baseline and 3.5 ± 0.7 mm at 12th month in DE-SS, 2.9 ± 0.7 mm at baseline and 9.5 ± 0.7 mm in DE-NSS groups at 12th month. Mean ST score was higher in DE-NSS group than DE-SS group at sixth and 12th months of the treatment (both p = 0.001). Tear break-up time score showed a significant improvement in DE-NSS group, and it was lower in DE-NSS group than DE-SS group group at sixth and 12th months of the treatment (p = 0.044 and 0.027, respectively). Mean OSDI score was lower in DE-NSS group than DE-SS group at sixth and 12th months of the treatment (p = 0.030 and 0.032, respectively). CONCLUSION: Topical CsA seems to be more effective in the treatment of the DE-NSS.
33467204 Immune Monitoring upon Treatment with Biologics in Sjögren's Syndrome: The What, Where, W 2021 Jan 16 Over the years, a wide variety of therapeutic antibodies has been successfully introduced in the auto-immunology clinic, and many more are on the way. Many of these treatments address either a pathogenic circulating molecule or a cell-bound molecule. Whereas addressing the former target results in neutralization of the soluble factor and binding to the latter target either inhibits cellular function or induces selective cell death. If this targeted molecule or cell is part of the immune system, this therapy evokes a state of immunodeficiency with infections as a possible consequence. Therefore, immune monitoring is needed to prevent such adverse side effects of immunotherapy. In this paper, different immunotherapies used in Sjögren's syndrome, as well as different approaches to monitoring the immune system, are discussed.
34441751 The Assessment of Muscle Mass and Function in Patients with Long-Standing Rheumatoid Arthr 2021 Aug 4 Muscular dysfunction in rheumatoid arthritis (RA) can affect the quality of life and comorbidities. We enrolled 320 patients with RA, and evaluated their muscle mass, grip strength, and physical performance. Seven (2.2%) and 21 RA patients (6.6%) had sarcopenia, as defined by the European and Asian Working Group for Sarcopenia (EWGS and AWGS), respectively; 54 patients (16.9%) were determined to have low muscle mass with normal muscle function, as defined by the EWGS; 38 patients (11.9%) reported sarcopenia by SARC-F questionnaire. Male sex (odds ratio (OR) 140.65), low body mass index (BMI) (OR 0.41), and use of tumor necrosis factor (TNF) inhibitors (OR 4.84) were associated with a low muscle mass as defined by the EWGS, while male sex, old age, and low BMI were associated with sarcopenia as defined by the AWGS. Old age (OR 1.11), high BMI (OR 1.13), and a high Disease Activity Score 28 (OR 1.95) were associated with sarcopenia as reported on the SARC-F. Male, low BMI, and use of TNF inhibitors were associated with a low muscle mass, while male sex, old age, and low BMI were associated with sarcopenia in patients with long-standing RA.
34397172 Vehicle Control as a Measure of Real-World Driving Performance in Patients with Rheumatoid 2021 Aug 16 OBJECTIVE: To quantify vehicle control as a metric of automobile driving performance in patients with rheumatoid arthritis (RA). METHODS: Naturalistic driving assessments were completed in patients with active RA and controls without disease. Data were collected using in-car, sensor-based instrumentation installed in the participants' own vehicles to observe typical driving habits. RA disease status, disease activity, and functional status were associated with vehicle control (lateral [steering] and longitudinal [braking/accelerating] acceleration variability [AV]) using mixed-effect linear regression models stratified by road type (defined by roadway speed limit). RESULTS: Across 1,292 driving hours, RA drivers (n=33) demonstrated differences in vehicle control compared to controls (n=23) with evidence of significant statistical interaction between disease status and road type (p<0.001). On residential roads, participants with RA demonstrated overall lower braking/accelerating variability than controls (p≤0.004) and, when disease activity was low, lower steering variability (p=0.03). On interstates/highways, RA was associated with increased steering variability among those with moderate/high CDAI scores (p=0.04). In models limited to RA, increases in disease activity and physical disability over 12-weeks of observation were associated with a significant increase in braking/accelerating variability on interstate/highways (both p<0.05). CONCLUSIONS: Using novel naturalistic assessments, we linked RA and worsening RA disease severity with aberrant vehicle control. These findings support the need for further research to map these observed patterns in vehicle control to metrics of driver risk, and, in turn, to link patterns of real-world driving behavior to diagnosis and disease activity.
34873316 Novel treatment for refractory rheumatoid arthritis with total glucosides of paeony and no 2021 Dec 6 Patients with refractory rheumatoid arthritis (RA) remain a substantial clinical problem, while the overexpression of P-glycoprotein (P-gp) on their lymphocytes may contribute to resistance to anti-rheumatic drugs. This study aims to develop a novel treatment for refractory RA consisting of the combination of total glucosides of paeony (TGPs) and the P-gp inhibitor nobiletin (N), which are codelivered in a self-nanoemulsifying drug delivery system (SNEDDS). Based on the solubility, compatibility, and pseudoternary phase diagram tests, a nano-SNEDDS formulation composed of capryol 90-cremophor EL35-tcranscutol HP (CET) to codeliver TGP and N was developed, and this formulation increased the bioavailability of TGP by 435.04% (indicated with paeoniflorin). A modified adjuvant-induced arthritis (AIA) rat model was verified for the overexpression of P-gp in lymphocytes and resistance to methotrexate (MTX) treatment at the reported anti-inflammatory dosage. CET formulation not only increased the solubility and permeability of TGP but also inhibited the function and expression of P-gp, leading to enhanced bioavailability and intracellular concentration in the lymphocytes of AIA rats and consequently boosting the anti-arthritic effects of TGP. Moreover, TGP and N coloaded CET reduced the expression of P-gp in AIA rats partly by inhibiting the phosphorylated AKT and HIF-1α pathways. In summary, TGP-N coloaded SNEDDS is a novel and effective treatment for refractory RA.
34501253 Decision-Making Strategy for the Treatment of Rheumatoid Arthritis-Associated Interstitial 2021 Aug 25 Rheumatoid arthritis (RA) is a common type of autoimmune arthritis. Patient clinical outcomes might be influenced by numerous respiratory diseases, but interstitial lung disease (ILD) is the most important comorbidity. RA-associated ILD (RA-ILD) is divided into acute/subacute and chronic forms. In the acute/subacute course, if the disease is severe as indicated by a diffuse alveolar damage pattern, high-dose corticosteroids combined with antimicrobial agents should be promptly initiated while considering the differential diagnoses, primarily acute exacerbation (AE) of RA-ILD, drug-induced pneumonitis, and Pneumocystis pneumonia. As initial therapeutic management in the chronic course, the RA itself should be stabilized without delay; thereafter, the activity of ILD itself can be stabilized, considering the safety of each anti-rheumatic drug. The formation of the usual interstitial pneumonia (UIP) pattern is the most important determinant because lung function can worsen more quickly with this pattern. However, because clinicians can fail to identify specific radiological patterns, it is important to determine whether each patient with RA-ILD has UIP-like lesions such as subpleural reticulation, traction bronchiectasis, and honeycombing especially progressively enlarged cysts. In patients with progressive RA-ILD and high risk for infection or AE of ILD in whom fibrosis is dominant, clinicians should consider starting an anti-fibrotic agent.
33373915 Yishen-tongbi decoction inhibits excessive activation of B cells by activating the FcγRII 2021 Feb Rheumatoid arthritis (RA) is a chronic autoimmune disease. Strong evidence supports that excessive activation of B cells plays a critical role in the pathogenesis of RA. Fc gamma receptor b (FcγRIIb) is the B cell inhibitory receptor and inhibits BCR (B cell receptor) signalling in part by selectively dephosphorylating CD19 which is considered a co-receptor for BCR and is essential for B cell activation. Our previous study demonstrated that a FcγRIIb I232T polymorphism presented a strong genetic link to RA and may lead to the excessive activation of B cells. Therefore, novel therapeutic strategies and drugs that can effectively inhibit the excessive activation of B cells by regulating the FcγRIIb are necessary for the treatment of RA. Therefore, we used Burkitt's lymphoma ST486 human B cells (lacking endogenous FcγRIIb) transfected with the 232Thr loss-of-function mutant to construct a FcγRIIb mutant cell line (ST486), and we demonstrated that YSTB treatment not only reduced proliferation and promoted apoptosis in ST486 cells but also did so in a dose-dependent manner. Furthermore, the intracellular Ca(2+) flux of ST486 cells was decreased after treatment with YSTB, inhibiting the excessive activation of ST486 cells, and these effects correlated with the CD19/FcγRIIb-Lyn-SHP-1 pathways. Our data showed that YSTB treatment inhibited the expression of phosphorylated CD19 and upregulated the protein expression of FcγRIIb, Lyn, and SHP-1. Additionally, the CIA model was established to explore the anti-inflammatory and inhibitory effects of YSTB on bone destruction, and we found that YSTB decreased the paw oedema and arthritis index (AI) in CIA rats. It is worth mentioning that YSTB clearly decreased the AI earlier than methotrexate (MTX) (day 10 vs 16). Moreover, synovial hyperplasia, inflammatory cell infiltration and cartilage surface erosion in CIA rats were noticeably reduced after treatment with YSTB as evidenced by histopathological examination. Finally, we found that YSTB treatment suppressed bone erosion and joint space score (JNS) in CIA rats as evidenced by radiographic assessment. In summary, these data suggest that YSTB has great therapeutic potential for RA treatment.
31103432 Update of the Mexican College of Rheumatology Guidelines for the Pharmacological Treatment 2021 Apr Therapeutic advances in rheumatoid arthritis require periodic review of treatment guidelines. OBJECTIVE: To update the Mexican College of Rheumatology guidelines on the pharmacological treatment of rheumatoid arthritis. METHOD: Board certified rheumatologists from different health institutions and regions of the country participated. Work teams were formed that reviewed the previous guidelines, elaborated new questions, reviewed the literature, and scored the evidence that was presented and discussed in plenary session. The conclusions were presented to infectologists, gynaecologists and patients. Recommendations were based on levels of evidence according to GRADE methodology. RESULTS: Updated recommendations on the use of available medications for rheumatoid arthritis treatment in Mexico up to 2017 are presented. The importance of adequate and sustained control of the disease is emphasized and relevant safety aspects are described. Bioethical conflicts are included, and government action is invited to strengthen correct treatment of the disease. CONCLUSIONS: The updated recommendations of the Mexican College of Rheumatology on the pharmacological treatment of rheumatoid arthritis incorporate the best available information to be used in the Mexican health care system.
33815108 The Influence of Treatment of Inflammatory Arthritis During Pregnancy on the Long-Term Chi 2021 The management of reproductive issues in women with inflammatory arthritis has greatly changed over decades. In the 1980-1990s, women with refractory forms of arthritis were either not able to get pregnant or did choose not to get pregnant because of their disabling disease. Hence, the traditional belief that pregnancy can induce a remission of arthritis. The availability of biologic agents has allowed a good control of aggressive forms of arthritis. The main topic of discussion during preconception counselling is the use of drugs during pregnancy and breastfeeding. Physicians are now supported by international recommendations released by the European League Against Rheumatism and the American College of Rheumatology, but still they must face with cultural reluctance in accepting that a pregnant woman can take medications. Patient-physician communication should be centered on the message that active maternal disease during pregnancy is detrimental to fetal health. Keeping maternal disease under control with drugs which are not harmful to the fetus is the best way to ensure the best possible outcome for both the mother and the baby. However, there might be concerns about the influence of the in utero exposure to medications on the newborn's health conditions. Particularly, studies suggesting an increased risk of autism-spectrum-disorders in children born to women with rheumatoid arthritis has raised questions about neuropsychological impairment in the offspring of women with chronic arthritis. As a multidisciplinary group of rheumatologists and child neuropsychiatrists, we conducted a study on 16 women with chronic forms of arthritis whose diagnosis was determined before pregnancy and their 18 school-age children. The children underwent a complete neurological examination and validated tests/questionnaires. Behavioral aspects of somatization and anxiety/depression (internalizing problem) or an "adult profile" were found in nearly one third of children. Children at a high risk of neurodevelopmental problems were born to mothers with a longer history of arthritis and were breastfeed for less than 6 months of age or were not breastfeed at all. No association was found with other maternal characteristics such as autoantibody existence and disease activity during and after the pregnancy.
34977255 VDR Polymorphisms in Autoimmune Connective Tissue Diseases: Focus on Italian Population. 2021 Vitamin D is an important hormone involved in various physiologic processes, and its activity is linked to binding with vitamin D receptor (VDR). Genetic polymorphisms in the VDR gene could modulate the expression or function of the receptor and, consequently, alter the effects of vitamin D. Variants in VDR gene have been associated with susceptibility to many illnesses sensitive to vitamin D administration and to autoimmune disorders, but no data are available regarding autoimmune connective tissue diseases in Italian population. We analyzed three VDR polymorphisms in 695 Italian patients with autoimmune connective tissue diseases (308 with systemic lupus erythematosus (SLE), 195 with primary Sjogren's syndrome (pSS), and 192 with rheumatoid arthritis (RA)) and in 246 healthy controls with the aim to evaluate a possible association of VDR SNPs with susceptibility to these diseases in the Italian population. Genotyping of rs2228570, rs7975232, and rs731236 in VDR gene was performed by an allelic discrimination assay. A case/control association study and a genotype/phenotype correlation analysis have been performed. We observed a higher risk to develop SLE for rs2228570 TT genotype (P = 0.029, OR = 1.79). No association was observed between susceptibility to pSS or RA and this SNP, although this variant is significantly less present in RA patients producing autoantibodies. For rs7975232 SNP, we observed a significant association of the variant homozygous genotype with SLE (P = 0.009, OR = 1.82), pSS (P = 0.046, OR = 1.66), and RA (P = 0.028, OR = 1.75) susceptibility. Moreover, we reported associations of this genotype with clinical phenotypes of SLE and pSS. Lastly, the GG genotype of rs731236 was associated with a lower RA susceptibility (P = 0.045, OR = 0.55). Our results show that the explored VDR polymorphisms are significantly associated with autoimmune connective tissue disorders and support the hypothesis that the genetic variability of VDR gene may be involved in susceptibility to these diseases in Italian population.
34975855 Fibrinogen-Like Protein 1 Serves as an Anti-Inflammatory Agent for Collagen-Induced Arthri 2021 Fibrinogen-like protein 1 (FGL1) was recently identified as a major ligand of lymphocyte-activation gene-3 (LAG-3) on activated T cells and serves as an immune suppressive molecule for regulation of immune homeostasis. However, whether FGL1 has therapeutic potential for use in the T cell-induced the autoimmune disease, rheumatoid arthritis (RA), is still unknown. Here, we attempted to evaluate the effect of FGL1 protein on arthritis progression. We also evaluated potential adverse events in a collagen-induced arthritis (CIA) mouse model. We first confirmed that soluble Fgl1 protein could specifically bind to surface Lag-3 receptor on 3T3-Lag-3 cells and further inhibit interleukin (IL-2) and interferon gamma (IFNγ) secretion from activated primary mouse T cells by 95% and 43%, respectively. Intraperitoneal administration of Fgl1 protein significantly decreased the inflammatory cytokine level (i.e., IL-1β and IL-6) in local paw tissue, and prevented joint inflammation, cellular infiltration, bone deformation and attenuated collagen-induced arthritis progression in vivo. We further demonstrated that exogenous Fgl1 does not cause obvious adverse events during treatment by monitoring body weight and liver weight, and assessing the morphology of several organs (i.e., heart, liver, spleen, lung and kidney) by pathological studies. We expect that Fgl1 protein may be suitable to serve as a potential therapeutic agent for treatment of RA or even other types of T cell-induced autoimmune or inflammatory diseases in the future.
34864896 Risk of flare after tapering or withdrawal of b-/tsDMARDs in patients with RA or axSpA: A 2021 Dec 3 OBJECTIVE: To evaluate flare risk when tapering or withdrawing biological or targeted synthetic disease-modifying antirheumatic drugs (b-/tsDMARDs) compared to continuation in patients with inflammatory arthritis (IA) in sustained remission or low disease activity. METHODS: Articles were identified in Cochrane Library, PubMed, EMBASE and Web of Science. Eligible trials were randomised, controlled trials comparing tapering and/or withdrawal of b- and/or tsDMARDs with standard dose in IA. Random-effects meta-analysis was performed with risk ratio (RR), or Peto's Odds Ratio (POR) for sparse events, and 95% confidence intervals (95%CI). RESULTS: The meta-analysis comprised 22 trials: 11 assessed tapering and 7 addressed withdrawal (4 assessed both). Only trials with a rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) population were identified. An increased flare risk was demonstrated when b-/tsDMARD tapering was compared to continuation, RR = 1.45 (95%CI: 1.19 to 1.77, I2 = 42.5%), and potentially increased for persistent flare, POR = 1.56 (95%CI: 0.97 to 2.52, I2 = 0%). Comparing tumour necrosis factor inhibitor (TNFi) withdrawal to continuation, a highly increased flare risk (RR = 2.28, 95%CI: 1.78 to 2.93, I2 = 78%) and increased odds of persistent flare (POR = 3.41, 95%CI: 1.91 to 6.09, I2 = 49%) was observed. No clear difference in flare risk between RA or axSpA was observed. CONCLUSION: A high risk for flare and persistent flare was demonstrated for TNFi withdrawal whereas an increased risk for flare but not for persistent flare was observed for b-/tsDMARD tapering. Thus, tapering seems to be the more favourable approach. REGISTRATION: PROSPERO (CRD42019136905).
34895310 Interferon-γ induces interleukin-6 production by neutrophils via the Janus kinase (JAK)-s 2021 Dec 11 OBJECTIVE: Interferon-gamma (IFN-γ) is overexpressed in rheumatoid synovium and thought to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study, we examined our hypothesis that IFN-γ activates innate immune cells and upregulates inflammatory cytokines. Peripheral blood neutrophils were stimulated with IFN-γ in the presence or absence of Janus kinase (JAK) inhibitors. Interleukin-6 (IL-6) mRNA and protein expression were analyzed using real-time polymerase chain reaction (PCR) method and enzyme-linked immunosorbent assay. Protein phosphorylation of JAKs or STAT1 was assessed by Western blot using phospho-specific antibodies. RESULTS: IFN-γ stimulation induces IL-6 expression in protein and mRNA levels in human neutrophils. Furthermore, IFN-γ stimulation induces JAK1/JAK2 phosphorylation and downstream signal transducer and activator of transcription (STAT) 1 phosphorylation in human neutrophils. Although all JAKi, blocked IFN-γ-induced JAK1.2/STAT1 phosphorylation at higher concentrations (100 nM), baricitinib most efficiently inhibited IFN-γ-induced JAK1.2/STAT1 phosphorylation at lower concentrations (≤ 25 nM). Among these JAKi, baricitinib was the most potent regulator for IFN-γ-induced IL-6 production in human neutrophils. Our data indicate that IFN-γ upregulates IL-6 production via the JAK1/2-STAT1 pathway in human innate immune cells. Furthermore, this IFN-γ-mediated IL-6 induction via JAK/STAT was downregulated by JAKi.
34386323 Targeted inhibition of GRK2 kinase domain by CP-25 to reverse fibroblast-like synoviocytes 2021 Jul Rheumatoid arthritis (RA) is an autoimmune disease and is mainly characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS). The up-regulated cellular membrane expression of G protein coupled receptor kinase 2 (GRK2) of FLS plays a critical role in RA progression, the increase of GRK2 translocation activity promotes dysfunctional prostaglandin E4 receptor (EP4) signaling and FLS abnormal proliferation. Recently, although our group found that paeoniflorin-6'-O-benzene sulfonate (CP-25), a novel compound, could reverse FLS dysfunction via GRK2, little is known as to how GRK2 translocation activity is suppressed. Our findings revealed that GRK2 expression up-regulated and EP4 expression down-regulated in synovial tissues of RA patients and collagen-induced arthritis (CIA) rats, and prostaglandin E2 (PGE2) level increased in arthritis. CP-25 could down-regulate GRK2 expression, up-regulate EP4 expression, and improve synovitis of CIA rats. CP-25 and GRK2 inhibitors (paroxetine or GSK180736A) inhibited the abnormal proliferation of FLS in RA patients and CIA rats by down-regulating GRK2 translocation to EP4 receptor. The results of microscale thermophoresis (MST), cellular thermal shift assay, and inhibition of kinase activity assay indicated that CP-25 could directly target GRK2, increase the protein stability of GRK2 in cells, and inhibit GRK2 kinase activity. The docking of CP-25 and GRK2 suggested that the kinase domain of GRK2 might be an important active pocket for CP-25. G201, K220, K230, A321, and D335 in kinase domain of GRK2 might form hydrogen bonds with CP-25. Site-directed mutagenesis and co-immunoprecipitation assay further revealed that CP-25 down-regulated the interaction of GRK2 and EP4 via controlling the key amino acid residue of Ala321 of GRK2. Our data demonstrate that FLS proliferation is regulated by GRK2 translocation to EP4. Targeted inhibition of GRK2 kinase domain by CP-25 improves FLS function and represents an innovative drug for the treatment of RA by targeting GRK2.
33852646 Correction: (In)Visible illness: A photovoice study of the lived experience of self-managi 2021 [This corrects the article DOI: 10.1371/journal.pone.0248151.].
34550600 The molecular structure and role of LECT2 or CHM-II in arthritis, cancer, and other diseas 2022 Jan Leukocyte cell-derived chemotaxin-2 (LECT2 or LECT-2), also called chondromodulin II (ChM-II or CHM2) plays a versatile role in various tissues. It was first identified as a chemotactic factor to promote the migration of neutrophils. It was also reported as a hepatokine to regulate glucose metabolism, obesity, and nonalcoholic fatty liver disease. As a secreted factor, LECT2 binds to several cell surface receptors CD209a, Tie1, and Met to regulate inflammatory reaction, fibrogenesis, vascular invasion, and tumor metastasis in various cell types. As an intracellular molecule, it is associated with LECT2-mediated amyloidosis, in which LECT2 misfolding results in insoluble fibrils in multiple tissues such as the kidney, liver, and lung. Recently, LECT2 was found to be associated with the development of rheumatoid arthritis and osteoarthritis, involving the dysregulation of osteoclasts, mesenchymal stem cells, osteoblasts, chondrocytes, and endothelial cells in the bone microenvironment. LECT2 is implicated in the development of cancers, such as hepatocellular carcinoma via MET-mediated PTP1B/Raf1/ERK signaling pathways and is proposed as a biomarker. The mechanisms by which LECT2 regulates diverse pathogenic conditions in various tissues remain to be fully elucidated. Further research to understand the role of LECT2 in a tissue tropism-dependent manner would facilitate the development of LECT2 as a biomarker for diagnosis and therapeutic target.
34427895 Treatment Patterns and Resource Utilization of Pregnant Women with Inflammatory Rheumatic 2021 Dec BACKGROUND: Uncontrolled inflammatory disease activity can impact pregnancy outcomes and the health of the mother and child. This retrospective claims database analysis assessed treatment patterns before, during, and after pregnancy among women with inflammatory rheumatic disease (IRD; axial spondyloarthritis [axSpA], psoriatic arthritis [PsA], and rheumatoid arthritis [RA]) or psoriasis (PSO) in Germany. METHODS: Data were extracted from the BARMER sickness fund (2013-2017). Pregnant women (18-45 years) with documented IRD or PSO diagnoses were compared with age-matched controls from the same database for the analysis of patient characteristics, healthcare resource utilization, and pharmacological treatment during pregnancy. Reported measures included the proportion of women with pharmacological prescriptions or hospitalization/new prescription of corticosteroids or biologics in the 180 days before pregnancy, during pregnancy, and 180 days after delivery. Pre-specified prescription categories (such as disease-specific drugs [not including biologics]) were identified by anatomical therapeutic chemical classification codes. Extrapolated values to the German statutory health insurance population are reported. RESULTS: Overall, 2702 pregnant women with IRD (axSpA: 1063; PsA: 660; RA: 979) and 6527 with PSO were identified. The proportion of women with IRD receiving prescriptions for disease-specific drugs reduced during pregnancy and remained stable after delivery (before: 15.0%; during: 9.0%; after: 9.7%). The proportion of women with PSO receiving prescriptions for disease-specific drugs was low (before: 0.6%; during: 0.3%; after: 0.1%). The proportion of women with hospitalization/new prescription of corticosteroids or biologics decreased during pregnancy, compared with pre-pregnancy, and increased after delivery in women with IRD (before: 9.0%; during: 5.1%; after: 11.1%) and PSO (before: 3.5%; during: 1.9%; after: 2.7%). CONCLUSIONS: A reduction in pharmacological treatment during pregnancy was observed for women with IRD in Germany. Many women with IRD did not return to pre-pregnancy treatments after delivery, despite signs of disease exacerbation, such as hospitalization and initiation of treatment with corticosteroids/biologics, in this period.