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ID PMID Title PublicationDate abstract
35156632 Tracheobronchopathia osteochondroplastica and cervical spine involvement in rheumatoid art 2022 Feb 14 Concurrent use of tumor necrosis factor inhibitor and tyrosine kinase inhibitor in ankylosing spondylitis and myeloid neoplasm.
35586186 Pharmacokinetics and Safety of Single and Multiple Doses of Peficitinib (ASP015K) in Healt 2022 OBJECTIVE: To investigate the pharmacokinetics and safety of peficitinib (Janus kinase inhibitor for the treatment of rheumatoid arthritis) in healthy Chinese subjects following single and multiple doses. METHODS: This open-label, randomized study was conducted at one site in China. Subjects received peficitinib 50, 100 or 150 mg as a single dose on Day 1 (fasted) and once daily from Days 8 to 13 in the multiple-dose period (fed). Blood samples were collected before administration each day, and up to 72h post administration. Pharmacokinetic assessments included area under the concentration curve (AUC), half-life (t(1/2)), maximum concentration (C(max)), and time to maximum concentration (t(max)) of peficitinib and its metabolites (H1, H2 and H4). Treatment-emergent adverse events (TEAEs) were evaluated. RESULTS: Thirty-six subjects were enrolled (12 per dose group). After a single dose of peficitinib, median t(max) was 1.0-1.5h and mean t(1/2) was 7.4-13.0h for all doses. In the multiple-dose period, median t(max) was 1.5-2.0h. Dose-proportional increases in C(max) and AUC(24h) were observed for peficitinib and its metabolites following single and multiple doses, with minimal drug accumulation. The major metabolite was H2, with a systemic exposure of >150% of the parent AUC. Drug-related TEAEs were experienced by 5 (13.9%) and 12 (33.3%) subjects in the single- and multiple-dose periods, respectively. Following multiple doses of peficitinib, TEAEs were more frequent in higher than lower dose groups but were mild in severity with no related discontinuation or death. CONCLUSION: Following single and multiple doses of peficitinib in healthy Chinese subjects, peficitinib demonstrated rapid absorption and was well tolerated at all doses. CLINICALTRIALSGOV IDENTIFIER: NCT04143477.
35107766 Polyene Phosphatidylcholine Interacting with TLR-2 Prevents the Synovial Inflammation via 2022 Feb 2 Rheumatoid arthritis (RA) is a chronic autoimmune joint disease that causes cartilage and bone damage or even disability, seriously endangering human health. Chronic synovial inflammation has been shown to play a vital role in disease sustainability. Therefore, downregulation of synovial inflammation is considered to be an effective discipline for RA therapy. Polyene phosphatidylcholine (PPC) is a hepatoprotective agent, which was observed to inhibit inflammation in macrophages and prevent collagen-induced arthritis (CIA) of rats in our previous study. However, the underlying mechanism remains unclear. The present study further reported that PPC can inhibit synovial inflammation. In lipopolysaccharide (LPS)-stimulated primary synovial fibroblasts (SFs) of mice, PPC significantly decreased pro-inflammatory cytokines production while increasing anti-inflammatory cytokines level. In this process, PPC downregulated the expression of TLR-2 and their downstream signaling molecules such as MyD88, p-ERK1/2, p-JNK1/2, and p-P38 in MAPK pathway and p-IκBα and NF-κB-p65 in NF-κB pathway. Moreover, the inhibitory effect of PPC on the above molecules and cytokines was weakened after pre-treatment with TLR-2 agonist Pam3CSK4. In addition, PPC lost its anti-inflammatory effect and its suppressing capability on MAPK and NF-κB pathways in TLR-2(-/-) primary SFs after exposure to LPS. Collectively, this study demonstrated that PPC can alleviate synovial inflammation through TLR-2-mediated MAPK and NF-κB pathways, which can be proposed to be a potential drug candidate for RA prevention.
35502428 Exploring Factors Influencing Medication Compliance in Saudi Rheumatoid Arthritis Patients 2022 PURPOSE: Compliance is essential to achieve treatment goals in rheumatoid arthritis (RA) patients. The current study evaluated compliance and related factors in a large and diverse population. PATIENTS AND METHODS: Patients with RA who received active treatment were invited to participate in an online survey. The Arabic versions of the 5-Item Compliance Questionnaire for Rheumatology (ACQR-5) and the RA Impact of Disease (RAID) were used to measure compliance and disability, respectively. The patients were sub-grouped based on background disease-modifying anti-rheumatic drugs (DMARDs). Variables associated with high compliance were selected for the logistic regression analysis. RESULTS: A total of 1241 patients completed the survey and were included in the final analysis. Of those, 1055 (85%) were females with a mean (±SD) age and disease duration of 47.14 ± 13.71 and 8.77 ± 7.43 years, respectively. The mean RAID was 4.4±2.58, with 980 (79%) having an unacceptable level state. Patients with an unacceptable RAID level had a lower compliance rate (78.8% vs 85.8%, p = 0.001). Demographics associated with high compliance were female sex and increased age, with reported odds ratios of 1.018 (95% CI: 1.007-1.028) and 1.464 (95% CI: 1.016-2.108), respectively. Compliance was similar between patients on Janus kinase inhibitors or biological DMARDs (88.14% vs 80.83%, p = 0.17), between monotherapy, double therapy, or triple therapy recipients (80% vs 82.23% vs 81.32%, p = 0.665), and between patients receiving injectable and oral therapy (77.32% vs 81.14%, p = 0.246). CONCLUSION: A high compliance level was observed in this population, with patient demographics influencing compliance rather than the medication type or route of administration. Interventional studies should focus on the of high-risk patients identified in this study.
35576644 Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor 2022 May 13 BACKGROUND: Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy. METHODS: Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients. FINDINGS: Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi. INTERPRETATION: Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems. FUNDING: The Instituto de Salud Carlos III.
35115930 The Effect and Safety of Iguratimod Combined With Methotrexate on Rheumatoid Arthritis: A 2021 Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with inflammatory synovitis. Iguratimod (IGU) combined with methotrexate (MTX) therapy may have better efficacy and safety. Methods: First, we searched randomized controlled trials (RCTs) of IGU + MTX in the treatment of RA through literature databases (such as PubMed, Corkland Library, CNKI, etc.) and then conducted RCT quality assessment and data extraction. Finally, we used RevMan 5.3 for meta-analysis, STATA 15.0 for publication bias assessment, and GRADE tool for the evidence quality assessment of primary outcomes. This systematic review and meta-analysis were registered in PROSPERO (CRD42021220780). Results: This systematic review and meta-analysis included 31 RCTs involving 2,776 patients. Compared with MTX alone, the ACR20, ACR50, and ACR70 of IGU + MTX are higher, while DAS28 is lower [ACR20: (RR 1.55, 95% CI 1.14-2.13, p = 0.006); ACR50: (RR 2.04, 95% CI 1.57-2.65, p < 0.00001); ACR70: (RR 2.19, 95% CI 1.44-3.34, p = 0.00003); DAS28: (weighted mean difference (WMD) -1.65, 95% CI -2.39 to -0.91, p < 0.0001)]. Compared with MTX + leflunomide, IGU + MTX has no significant difference in improving ACR20, ACR50, ACR70, but IGU + MTX improves DAS28 more significantly [ACR20: (RR 1.09, 95% CI 0.79-1.89, p = 0.59); ACR50: (RR 1.07, 95% CI 0.64-1.78, p = 0.81); ACR70: (RR 1.17, 95% CI 0.44-3.10, p = 0.76); DAS28: (WMD -0.40, 95% CI -0.42 to -0.38, p < 0.0001)]. Compared with the MTX + tripterygium subgroup and MTX-only subgroup, the incidence of adverse events of the IGU + MTX group is of no statistical significance [MTX only: (RR 0.99, 95% CI 0.87-1.13, p = 0.90); MTX + Tripterygium: (RR 0.73, 95% CI 0.29-1.85, p = 0.50)]. However, compared with MTX + leflunomide, the incidence of adverse events in the IGU + MTX group was lower (RR 0.74, 95% CI 0.62-0.88, p = 0.0009). The quality of ACR70 was high; the quality of adverse events and ACR50 test was moderate. Conclusion: Compared with conventional therapy, IGU + MTX may be a safer and more effective therapy for RA patients. When the intervention method is (IGU 25 mg Bid, MTX 10-25 mg once a week), and the intervention lasts for at least 12 weeks, the curative effect may be achieved without obvious adverse events.
35444638 Labial Gland Mesenchymal Stem Cell Derived Exosomes-Mediated miRNA-125b Attenuates Experim 2022 The pathogenesis of the prototypical chronic autoimmune disorder primary Sjögren syndrome (pSS) has been thought to be B-cell-centric, based on serum autoantibodies, the increased risk of B cell lymphoma, and altered B cell subsets in patients with pSS. Over the last 10 years, therapies targeting B cells have been investigated for pSS; however, current evidence for the efficacy of B cell targeted therapies in pSS is still sparse. Mesenchymal stem cells (MSCs) might represent a promising strategy for cell therapy of autoimmune diseases via regulation of immune cells. MSC-released exosomes carry various bioactive molecules and thus have been studied in MSC-based therapy. The newly discovered labial gland MSCs (LGMSCs) have exhibited enhanced performance. Herein, we aimed to determine the effects of LGMSC-derived exosomes (LGMSC-Exos) on the symptoms of a mouse model of pSS and their regulatory effect and mechanism on B cell subsets. In vivo, treatment of the spontaneous mouse model of pSS with LGMSC-Exos resulted in reduced inflammatory infiltration and restored saliva secretion in salivary glands. In vitro, coculture of LGMSC-Exos with peripheral blood mononuclear cells of patients with pSS markedly reduced the proportions of CD19(+)CD20(-)CD27(+)CD38(+) plasma cells among peripheral blood mononuclear cells. Further investigations provided evidence that LGMSC-Exo-derived microRNA-125b affected plasma cells of pSS by directly binding to its target gene, PRDM1 (PR domain zinc finger protein 1, also known as BLIMP1), which might be developed as a target to treat pSS. Overall, these findings provided a possible exploitable therapeutic target in pSS and provide new insights into the potential therapeutic application of exosomes in pSS and other disease mediated by B-cells.
35434592 SARS-Cov2 acute and post-active infection in the context of autoimmune and chronic inflamm 2022 The clinical and immunological spectrum of acute and post-active COVID-19 syndrome overlaps with criteria used to characterize autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Indeed, following SARS-Cov2 infection, the innate immune response is altered with an initial delayed production of interferon type I (IFN-I), while the NF-kappa B and inflammasome pathways are activated. In lung and digestive tissues, an alternative and extrafollicular immune response against SARS-Cov2 takes place with, consequently, an altered humoral and memory T cell response leading to breakdown of tolerance with the emergence of autoantibodies. However, the risk of developing severe COVID-19 among SLE and RA patients did not exceed the general population except in those having pre-existing neutralizing autoantibodies against IFN-I. Treatment discontinuation rather than COVID-19 infection or vaccination increases the risk of developing flares. Last but not least, a limited number of case reports of individuals having developed SLE or RA following COVID-19 infection/vaccination have been reported. Altogether, the SARS-Cov2 pandemic represents an unique opportunity to investigate the dangerous interplay between the immune response against infectious agents and autoimmunity, and to better understand the triggering role of infection as a risk factor in autoimmune and chronic inflammatory disease development.
35306230 Supra-lacrimal protein-based carriers for cyclosporine A reduce Th17-mediated autoimmunity 2022 Apr Sjögren's syndrome (SS) is a multifactorial autoimmune disease with principal symptoms including inflammation and loss of function of lacrimal glands (LG) and salivary glands. While glandular infiltrates includes both B- and T-cells, CD4(+) T cells are strongly implicated. Utilizing the male non-obese diabetic (NOD) mouse model of SS, this work: 1) identifies clinically-relevant elevations in cytokines (IL-17A, IL-2) in LG-derived CD4(+) T cells; and 2) explores tissue-specific immunosuppression of SS using a novel protein-based drug carrier to concentrate cyclosporine A (CsA) directly in the LG. As a potent immunosuppressant, topical ophthalmic CsA is approved for dry eye disorders; however, it cannot effectively resolve inflammation due to limited accumulation in the LG. Systemic CsA has dose-limiting side effects that also limit its ability to block LG inflammation. Using elastin-like polypeptides (ELPs) fused genetically to cyclophilin, the intracellular cognate receptor of CsA, this manuscript reports a sustained-release formulation of CsA that maintains therapeutic drug concentrations in the LG and extends intervals between doses. This formulation blocked both in vitro Th17 cell differentiation and IL-17A secretion. In vivo treatment significantly decreased the abundance of Th17.1 cells, a helper cell population sharing phenotypes of both Th17 and Th1, in the LG of diseased NOD mice. Treatment with even a single dose of the sustained-release formulation was effective enough to improve basal levels of tear production. Thus, this sustained-release formulation suppressed local LG inflammation driven through IL-17 dependent pathways, while improving ocular surface function.
35182269 Flare of adult-onset Still's disease following mRNA COVID-19 vaccination: a case report an 2022 May The upheaval caused by the coronavirus disease 2019 (COVID-19) pandemic has allowed to large population to use new vaccines urgently. Although vaccine development programs and available epidemiological data reassure us, there are concerns about specific risks associated with vaccinations in patients with autoimmune-autoinflammatory diseases. These patients have the potential to decrease humoral and cellular immune responses caused by biologic agents and develop an acute flare of underlying disease following vaccination. We herein present a rare case of a 49-year-old female with a flare of adult-onset Still's disease (AOSD) after the first dose of BNT162b2 mRNA COVID-19 vaccination. She had been diagnosed with AOSD 7 years earlier and had achieved remission with tocilizumab. This patient came to the emergency room with fever and nausea that occurred 4 days after the first vaccination. Based on laboratory results and clinical manifestations, we suspected AOSD flare and was treated with steroid pulse therapy. In this report, we also discuss possible mechanisms linking vaccination with a flare of AOSD. Considering the close time relationship between COVID-19 vaccinations and a flare of AOSD, physicians should be aware of adverse events from this new vaccination and evaluate the benefits and risks of vaccination for each patient. KEY POINTS: • COVID-19 vaccination may cause an AOSD flare in patients who are in remission with tocilizumab.
34651287 Plummer-Vinson syndrome in primary Sjögren syndrome: a case-based review. 2022 Feb This study aimed to describe a patient with Sjögren syndrome who developed Plummer-Vinson syndrome, and to review the literature and describe shared aspects of this rare association. A systematic screening of articles was conducted in PubMed/MEDLINE, LILACS, SciELO, Scopus, Web of Science, and Cochrane, dating 1940 to 2020. All the articles included the association between Sjögren syndrome and Plummer-Vinson syndrome. No language restriction was applied. The following terms were used: "Sjögren syndrome" or "sicca syndrome" and "Plummer-Vinson syndrome" or "Paterson-Kelly syndrome." We performed our analysis by adding our present case, with a total of 4 cases. Three out of four were female (75%), age varied from 56 to 58 years old. In 2 cases, Sjögren syndrome preceded Plummer-Vinson syndrome diagnosis, and in 1 report, Plummer-Vinson syndrome appeared before Sjögren syndrome. Disease duration varied from 7 to 20 years. In two cases, autoantibodies were available, and antinuclear antibodies and anti-Ro/SS-A were positive in both, and anti-La/SS-B in one of them was associated with anti-dsDNA; however, no data regarding lupus was available in the article. Treatment involved iron supplementation in 3/3. Two out of three received parenteral iron supplementation, and in these two cases, mechanical esophageal dilatation was needless. In the other case, an additional endoscopic esophageal dilatation was necessary to receive the oral iron supplement. All 3 cases had a good outcome. This case illustrates a patient with Sjögren syndrome who developed the rare Plummer-Vinson syndrome. In Sjögren syndrome, the presence of iron-deficiency anemia, dysphagia, and weight loss should alert the physician to search for associated Plummer-Vinson syndrome.
35020842 CMTM6: increased circulating level and up-regulated expression in labial salivary glands i 2022 Jan 28 Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing family member 6 (CMTM6), which is a key regulator of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling in patients with primary Sjögren's syndrome (pSS). In this study, we analyzed the serum levels of CMTM6, PD-1, and PD-L1 in 50 patients with pSS, 42 patients with non-pSS (simply dry mouth and/or eyes symptoms) and 50 healthy controls (HC). The expression of CMTM6, PD-1, and PD-L1 in labial glands of the same 50 pSS patients and 42 non-pSS patients were assessed by immunohistochemistry (IHC). The clinical significance of CMTM6, PD-1, and PD-L1 were analyzed. We found that levels of CMTM6, PD-L1 as well as PD-1 in sera were all increased significantly in patients with pSS compared with non-pSS controls and HC. Serum CMTM6 level showed significantly correlation with PD-L1, PD-1, as well as clinical laboratory indicators and disease activity of pSS patients. CMTM6, PD-1, and PD-L1 expression in labial glands was also higher significantly in pSS patients than non-pSS controls. pSS patients with higher CM grade or ESSDAI score have higher CMTM6, PD-L1, and PD-1 expression in labial glands. These results suggest that CMTM6 may affect peripheral tolerance and lymphocytes activation by PD-1/PD-L1 pathway in sera and target tissue in pSS.
34672336 Histopathology, salivary flow and ultrasonography of the parotid gland: three complementar 2022 May 30 OBJECTIVE: The involvement of salivary glands in primary SS (pSS) can be assessed in different ways: histopathology, salivary flow and ultrasonography. To understand the relative value of these different approaches, it is crucial to understand the relationship between them. As we routinely perform these three modalities in the parotid gland for disease evaluation, our aim was to investigate the construct validity between these modalities in one and the same gland. METHODS: Consecutive sicca patients underwent a multidisciplinary diagnostic workup including parotid gland biopsy, collection of parotid gland-specific saliva and parotid gland ultrasonography. Patients who were classified as pSS according to the ACR-EULAR criteria were included. Construct validity was assessed using Spearman's correlation coefficients. RESULTS: The 41 included pSS patients completed a full workup within a mean time interval of 2.6 months. Correlations between histopathological features and stimulated parotid salivary flow were fair (ρ = -0.123 for focus score and ρ = -0.259 for percentage of CD45+ infiltrate). Likewise, poor correlations were observed between stimulated parotid salivary flow and parotid ultrasonography (ρ = -0.196). Moderate to good associations were found between the histopathological items focus score and the percentage of CD45+ infiltrate, with parotid US scores (total US score: ρ = 0.510 and ρ = 0.560; highest for homogeneity: ρ = 0.574 and ρ = 0.633). CONCLUSION: Although pSS-associated ultrasonographic findings did correlate with histopathological features, the three modalities that evaluate salivary gland involvement assess different (or at best partly related) constructs. Therefore histopathology, salivary flow and ultrasonography are complementary measurements and cannot directly replace each other in the workup of pSS.
35366845 Acceptability of, and preferences for, remote consulting during COVID-19 among older patie 2022 Apr 2 BACKGROUND: Guidance for choosing face-to-face vs remote consultations (RCs) encourages clinicians to consider patient preferences, however, little is known about acceptability of, and preferences for RCs, particularly amongst patients with musculoskeletal conditions. This study aimed to explore the acceptability of, and preferences for, RC among patients with osteoporosis and rheumatoid arthritis. METHODS: Three UK qualitative studies, exploring patient experiences of accessing and receiving healthcare, undertaken during the pandemic, with people with osteoporosis and rheumatoid arthritis. Study team members agreed a consistent approach to conduct rapid deductive analysis using the Theoretical Framework of Acceptability (TFA) on transcripts from each data set relating to RC, facilitated by group meetings to discuss interpretations. Findings from the three studies were pooled. RESULTS: Findings from 1 focus group and 64 interviews with 35 people were included in the analysis. Participants' attitudes to RC, views on fairness (ethicality) and sense-making (intervention coherence) varied according to their needs within the consultation and views of the pandemic. Some participants valued the reduced burden associated with RC, while others highly valued non-verbal communication and physical examination associated with face-to-face consults (opportunity costs). Some participants described low confidence (self-efficacy) in being able to communicate in RCs and others perceived RCs as ineffective, in part due to suboptimal communication. CONCLUSIONS: Acceptability of, and preferences for RC appear to be influenced by societal, healthcare provider and personal factors and in this study, were not condition-dependant. Remote care by default has the potential to exacerbate health inequalities and needs nuanced implementation.
35091779 Abnormal Histones Acetylation in Patients with Primary Sjögren's Syndrome. 2022 May INTRODUCTION: Aberrant histone acetylation is increasingly thought to play important roles in the pathogenesis of autoimmune diseases. However, there are very few data on histone acetylation in primary Sjögren's syndrome (pSS). We aimed to investigate whether there was abnormal histones acetylation in patients with pSS. METHODS: We investigated the expressions of histone acetyltransferase (HAT) genes (p300, CREBBP and PCAF) by real-time PCR in the peripheral blood mononuclear cells (PBMCs) of pSS patients. HAT activity and histone H3/H4 acetylation activity were measured by activity kit, and histone H3/H4 acetylation was verified by Western blot (WB). Spearman test was utilized to analyze the association between HAT activity levels and clinical parameters of pSS patients. RESULTS: The mRNA expressions of p300, CREBBP and PCAF in PBMCs from pSS patients were decreased in comparison with healthy controls (P < 0.05). HAT activity and histone H3/H4 acetylation were reduced in PBMCs from pSS patients (P < 0.05). We found that HAT activity was negatively correlated with CRP (P = 0.040) and TNF-α (P = 0.012), and was positively correlated with C4 (P = 0.041). CONCLUSIONS: Histone hypoacetylation is observed in patients with pSS and is involved in the pathogenesis of pSS. KEY POINTS: • The mRNA expressions of p300, CREBBP and PCAF in PBMCs from pSS patients were decreased in comparison with HCs. • HAT activity and histone H3/H4 acetylation were reduced in PBMCs from pSS patients. • HAT activity was correlated with disease characters. • We show for the first time that the histone hypoacetylation may be involved in the pathogenesis of pSS.
34780913 Plasmacytoid dendritic cells promote the pathogenesis of Sjögren's syndrome. 2022 Feb 1 Plasmacytoid dendritic cells (pDCs) produce type I interferons (IFNs) and promote pathogenesis of multiple autoimmune diseases. Autoimmune Sjögren's syndrome (SS) primarily affects salivary and lacrimal glands, causing their inflammation, destruction and dysfunction. pDCs and type I IFN activity are elevated in salivary glands of SS patients, and this study seeks to elucidate the in vivo actions of pDCs in SS pathogenesis using the non-obese diabetic (NOD) mouse model. We confirmed the type I IFN-dependency of SS development in female NOD mice and elevation of pDC-type I IFN in their submandibular glands (SMGs). We administered a pDC-depleting anti-BST2/CD317 antibody to female NOD mice from 4 to 7 weeks of age at the early stage of SS, and assessed SS pathologies at age 10 weeks, the time of disease onset. Depletion of pDCs impeded the development of SMG inflammation and secretory dysfunction. It drastically reduced the amount of type I IFN mRNA and the number of total leukocytes, and T- and B lymphocytes in SMGs. Gene expression analyses showed that pDC depletion markedly diminished SMG expression of IL-7, BAFF, TNF-α, IFN-γ, CXCL9, CXCL11, CD40, CD40L, Lt-α, Lt-β and NOS2. Hence, pDCs critically contribute to the development and onset of SS-like salivary gland exocrinopathy.
35531186 Inhibition of Porphyromonas gingivalis peptidyl arginine deiminase, a virulence factor, by 2022 Apr Porphyromonas gingivalis, the cause of periodontitis, is also linked to many systemic disorders due to its citrullination capability from a unique peptidyl arginine deiminase (PPAD). Protein citrullination is able to trigger an autoimmune response, increasing the severity of rheumatoid arthritis. The main objective of this study is to evaluate the inhibitory activity of Cratoxylym cochinchinense leaves extract towards the PPAD in vitro and in silico. Methanolic extract of Cratoxylum cochinchinense (CCM) was tested for total phenolic and flavonoid contents along with antioxidative assays. Inhibition of PPAD activities was conducted thereafter using recombinant PPAD in cell lysate. Phytocompounds postulated present in the CCM such as mangiferin, vismiaquinone A, δ-tocotrienol and α-tocotrienol and canophyllol were used as ligands in a simulated docking study against PPAD. Results obtained indicated high antioxidant potential in CCM while recording abundant phenolic (129.0 ± 2.5495 mg GA/g crude extract) and flavonoid (159.0 ± 2.1529 mg QE/g crude extract) contents. A dose-dependent inhibition of PPAD was observed when CCM was evaluated at various concentrations. CCM at 1 mg/mL exhibited citrulline concentration of 24.37 ± 3.25 mM which was 5 times lower than the negative control (114.23 ± 3.31 mM). Molecular docking simulation revealed that mangiferin and vismiaquinone A engaged in H-bonding and pi-pi interactions with important active site residues (Asp130, Arg152, Arg154 and Trp127) of PPAD and could be the potential phytochemicals that accounted for the inhibitory activities observed in the methanolic leaves extract. As such, CCM could be further explored for its therapeutic properties not only for periodontitis, but also for other systemic diseases like rheumatoid arthritis.
35628866 Adiponectin Is a Component of the Inflammatory Cascade in Rheumatoid Arthritis. 2022 May 12 Adiponectin is a secretory protein of adipocytes that plays an important role in pathological processes by participation in modulating the immune and inflammatory responses. The pro-inflammatory effect of adiponectin is observed in rheumatoid arthritis (RA). In this study, we examined adiponectin plasma levels and the expression of adiponectin in bone marrow tissue samples, synovium samples, and infrapatellar fat pad samples from patients with osteoarthritis (OA) and RA. Additionally we examined the expression of adiponectin receptors AdipoR1 and AdipoR2 in synovium samples and infrapatellar fat pad samples from patients with OA and RA. We also assessed the correlations between adiponectin plasma concentrations, adiponectin expression in bone marrow, synovium, infrapatellar fat pad, and plasma levels of selected cytokines. We found increased expression of adiponectin in synovium samples and infrapatellar fat pad samples from patients with RA as compared to patients with OA. There were no statistically significant differences of adiponectin plasma levels and adiponectin expression in bone marrow tissue samples between OA and RA patients. There were no differences in the expression of AdipoR1 and AdipoR2 at the mRNA level in synovial tissue and the infrapatellar fat pad between RA and OA patients. However, in immunohistochemical analysis in samples of the synovial membrane from RA patients, we observed very strong expression of adiponectin in intima cells, macrophages, and subintimal fibroblasts, such as synoviocytes, vs. strong expression in OA samples. Very strong expression of adiponectin was also noted in adipocytes of Hoffa's fat pad of RA patients. Expression of AdipoR1 was stronger in RA tissue samples, while AdipoR2 expression was very similar in both RA and OA samples. Our results showed increased adiponectin expression in the synovial membrane and Hoffa's pad in RA patients compared to that of OA patients. However, there were no differences in plasma adiponectin concentrations and its expression in bone marrow. The results suggest that adiponectin is a component of the inflammatory cascade that is present in RA. Pro-inflammatory factors enhance the expression of adiponectin, especially in joint tissues-the synovial membrane and Hoffa's fat pad. In turn, adiponectin also increases the expression of further pro-inflammatory mediators.
35404026 Prediction of diagnosis results of rheumatoid arthritis patients based on autoantibodies a 2022 Apr 11 OBJECTIVES: To analyze and evaluate the effectiveness of the detection of single autoantibody and combined autoantibodies in patients with rheumatoid arthritis (RA) and related autoimmune diseases and establish a machine learning model to predict the disease of RA. METHODS: A total of 309 patients with joint pain as the first symptom were retrieved from the database. The effectiveness of single and combined antibodies tests was analyzed and evaluated in patients with RA, a cost-sensitive neural network (CSNN) model was used to integrate multiple autoantibodies and patient symptoms to predict the diagnosis of RA, and the ROC curve was used to analyze the diagnosis performance and calculate the optimal cutoff value. RESULTS: There are differences in the seropositive rate of autoimmune diseases, the sensitivity and specificity of single or multiple autoantibody tests were insufficient, and anti-CCP performed best in RA diagnosis and had high diagnostic value. The cost-sensitive neural network prediction model had a sensitivity of up to 0.90 and specificity of up to 0.86, which was better than a single antibody and combined multiple antibody detection. CONCLUSION: In-depth analysis of autoantibodies and reliable early diagnosis based on the neural network could guide specialized physicians to develop different treatment plans to prevent deterioration and enable early treatment with antirheumatic drugs for remission. Key Points • There are differences in the seropositive rate of autoimmune diseases. • This is the first study to use a cost-sensitive neural network model to diagnose RA disease in patients. • The diagnosis effect of the cost-sensitive neural network model is better than a single antibody and combined multiple antibody detection.
35204444 Antibodies against 4 Atypical Post-Translational Protein Modifications in Patients with Rh 2022 Jan 29 Patients with rheumatoid arthritis (RA) show autoantibodies against post-translational protein modifications (PTMs), such as anti-citrullinated protein antibodies. However, the range of recognized PTMs is unknown. Here, we addressed four PTMs: chlorination, non-enzymatic glycation, nitration, and homocysteinylation, identified as targets of atypical RA autoantibodies in studies whose protocols we have followed. The modified antigens included collagen type II, an extract of synovial proteins and a selection of peptides. We interpreted the results according to the optical density (OD) obtained in an enzyme-linked immunosorbent assay ( ELISA) with the modified antigen and the corrected OD obtained after subtracting the reactivity against the unmodified antigen. The results showed evidence of specific antibodies against glycated collagen type II, as the corrected ODs were higher in the 182 patients with RA than in the 164 healthy controls (p = 0.0003). However, the relevance of these antibodies was doubtful because the magnitude of the specific signal was small (median OD = 0.072 vs. 0.027, respectively). There were no specific antibodies against any of the other three PTMs. Therefore, our results showed that the four PTMs are not inducing a significant autoantibody response in patients with RA. These results indicated that the repertoire of PTM autoantigens in RA is restricted.