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

ID PMID Title PublicationDate abstract
30893386 Psoriasis treatment in patients with sickle cell disease. 2019 Feb Plaque psoriasis is a chronic inflammatory disease driven by the proliferation of T cells and the production of several immunomodulators such as tumor necrosis factor (TNF) α. Tumor necrosis factor α plays a key role in multiple inflammatory conditions, including psoriatic arthritis, rheumatoid arthritis, and hidradenitis suppurativa. We present a patient with plaque psoriasis and sickle cell disease who began treatment with the TNF-α inhibitor adalimumab. With this treatment, the patient had improvement in both psoriasis and sickle cell disease symptoms. Tumor necrosis factor α inhibitors may be the drug of choice in patients with both psoriasis and sickle cell disease.
31597740 TNF receptor 2 signaling prevents DNA methylation at the Foxp3 promoter and prevents patho 2019 Oct 22 Regulatory T (Treg) cells expressing the transcription factor Foxp3 play an important role in maintaining immune homeostasis. Chronic inflammation is associated with reduced Foxp3 expression, function, and loss of phenotypic stability. Previous studies have established the importance of TNF receptor 2 (TNFR2) in the generation and/or activation of Treg cells. In this study, we assess the importance of TNFR2 in healthy mice and under inflammatory conditions. Our findings reveal that, in health, TNFR2 is important not only for the generation of Treg cells, but also for regulating their functional activity. We also show that TNFR2 maintains Foxp3 expression in Treg cells by restricting DNA methylation at the Foxp3 promoter. In inflammation, loss of TNFR2 results in increased severity and chronicity of experimental arthritis, reduced total numbers of Treg cells, reduced accumulation of Treg cells in inflamed joints, and loss of inhibitory activity. In addition, we demonstrate that, under inflammatory conditions, loss of TNFR2 causes Treg cells to adopt a proinflammatory Th17-like phenotype. It was concluded that TNFR2 signaling is required to enable Treg cells to promote resolution of inflammation and prevent them from undergoing dedifferentiation. Consequently, TNFR2-specific agonists or TNF1-specific antagonists may be useful in the treatment of autoimmune disease.
30883507 Pharmacodynamic Monitoring of Biological Therapies in Chronic Inflammatory Diseases. 2019 Apr BACKGROUND: Psoriasis, psoriatic arthritis, spondyloarthritis, rheumatoid arthritis, ulcerative colitis, and Crohn disease share similar underlying pathophysiological processes, providing the opportunity to treat the patients using similar biological therapies. Failure of biological treatments due to underexposure can be managed by therapeutic drug monitoring. Adjusting the treatment based on pharmacokinetic monitoring can be further improved by taking pharmacodynamic parameters such as clinical and molecular markers into account. METHODS: Here, we critically evaluate the existing evidence, the hurdles to be taken, and the opportunities for a widespread implementation of pharmacodynamic monitoring. RESULTS: Pharmacodynamic monitoring typically is the monitoring of biochemical markers. A pharmacodynamic marker preferably is specific for the pharmacological action of a drug, but most of the time nonspecific pharmacodynamic markers are used, such as C-reactive protein and the erythrocyte sedimentation rate. Clinical pharmacodynamic markers typically evaluate physical variables or symptoms. Although physician-reported outcomes have been studied for a longer time and often have been shown to correlate well with molecular pharmacodynamic markers and treatment outcomes, the introduction of mobile health or mHealth technologies caused a shift toward patient-reported outcomes, with the associated challenge to consistently reflect the inflammatory state, thereby preventing undertreatment or unnecessary overdosing of patients. CONCLUSIONS: The primary goal of pharmacodynamic monitoring is to optimize the response, but it can also have an impact on safety, costs, patient adherence, etc. Ideally, the constant remote monitoring of patient-reported disease activity is expected to become the standard, facilitated by mHealth technologies.
30886989 Malignancy risk in Australian rheumatoid arthritis patients treated with anti-tumour necro 2019 BACKGROUND: Tumour necrosis factor inhibitor (TNFi) therapy has been available for rheumatoid arthritis (RA) patients for several decades but data on the long-term risk of malignancy associated with its use is limited. Our aims were to assess malignancy risk in a cohort of Australian RA patients relative to the Australian population and to compare cancer risk for patients exposed to TNFi therapy versus a biologic-naïve group. METHODS: Demographic data for RA participants enrolled in the Australian Rheumatology Association Database (ARAD) before 31 Dec 2012 were matched to national cancer records in May 2016 (linkage complete to 2012). Standardised incidence ratios (SIRs) were used to compare malignancy incidence in TNFi-exposed and biologic-naïve ARAD participants with the Australian general population using site-, age- and sex-specific rates by calendar year. Malignancy incidence in TNFi-exposed participants and biologic-naïve RA patients, were compared using rate ratios (RRs), adjusted for age, sex, smoking, methotrexate use and prior malignancy. RESULTS: There were 107 malignancies reported after 10,120 person-years in the TNFi-exposed group (N = 2451) and 49 malignancies after 2232 person-years in the biologic-naïve group (N = 574). Compared with the general population, biologic-naïve RA patients showed an increased risk for overall malignancy (SIR 1.52 (95% confidence interval (CI) 1.16, 2.02) prostate cancer (SIR 2.10, 95% CI 1.18, 4.12). The risk of lung cancer was increased for both biologic naïve and TNFi-exposed patients compared with the general population (SIR 2.69 (95% CI 1.43 to 5.68) and SIR 1.69 (95% CI 1.05 to 2.90) respectively). For the TNFi-exposed patients there was an increased risk of lymphoid cancers (SIR 1.82, 95% CI 1.12, 3.18). There were no differences between the exposure groups in the risk of cancer for any of the specific sites examined. CONCLUSIONS: Overall malignancy incidence was elevated for biologic-naïve RA patients but not for those exposed to TNFi. TNFi exposure did not increase malignancy risk beyond that experienced by biologic-naïve patients. Lung cancer risk was increased for both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status or RA treatments other than TNFi may be responsible in some way.
31212775 Achieving Pain Control in Rheumatoid Arthritis with Baricitinib or Adalimumab Plus Methotr 2019 Jun 12 The purpose of the study was to assess the proportion of patients who achieve pain relief thresholds, the time needed to reach the thresholds, and the relationship between pain and inflammation among patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate in RA-BEAM (NCT0170358). A randomized, double-blind trial was conducted, comparing baricitinib (N = 487), adalimumab (N = 330), and placebo (N = 488) plus methotrexate. Pain was evaluated by patient's assessment on a 0-100 mm visual analog scale (VAS). The following were assessed through a 24-week placebo-controlled period: the proportion of patients who achieved ≥30%, ≥50%, and ≥70% pain relief, the time to achieve these pain relief thresholds, remaining pain (VAS ≤ 10 mm, ≤20 mm, or ≤40 mm), and the relationship between inflammation markers and pain relief. Baricitinib-treated patients were more likely (p < 0.05) to achieve ≥30%, ≥50%, and ≥70% pain relief than placebo- and adalimumab-treated patients, as early as Week 1 vs. placebo and at Week 4 vs. adalimumab. A greater proportion of baricitinib-treated patients achieved ≤20 mm or ≤40 mm remaining pain vs. placebo- and adalimumab-treated patients. Baricitinib-treated patients tended to demonstrate consistent pain relief independent of levels of inflammation control. In RA patients with an inadequate response to methotrexate, baricitinib provided greater and more rapid pain relief than adalimumab and placebo. Analyses suggest the relationship between inflammation and pain may be different for baricitinib and adalimumab treatments.
31563017 Penta-acetyl geniposide induces apoptosis of fibroblast-like synoviocytes from adjuvant-in 2019 Dec BACKGROUND: Approaches promoting fibroblast-like synoviocytes (FLS) apoptosis are considered as a meaningful strategy for rheumatoid arthritis (RA) treatment. We have previously reported the anti-arthritic effect of penta-acetyl geniposide ((Ac)(5)GP, an active derivative of geniposide) on adjuvant-induced arthritis (AIA) rats in vivo. The present study aimed to investigate the pro-apoptotic effect of (Ac)(5)GP on AIA FLS in vitro and the underlying molecular mechanisms. METHODS: Rat AIA was induced by complete Freund's adjuvant, and FLS were primary-cultured from synovial tissues. AIA FLS were treated with (Ac)(5)GP (50, 100 and 200 μM) for 48 h and cell proliferation and apoptosis were respectively examined. The involvement of apoptosis-related proteins (Bax, Bcl-2 and caspase 3) and nuclear factor kappa B (NF-κB) signaling pathway was checked. RESULTS: (Ac)(5)GP inhibited the viability of AIA FLS and reduced the percentage of Ki67-positive cells in AIA FLS. Particularly, (Ac)(5)GP promoted AIA FLS apoptosis in vitro by inducing apoptotic nuclear morphology, facilitating DNA ladder formation and increasing percentages of both early and late apoptotic cells. (Ac)(5)GP treatment on AIA FLS decreased Bcl-2 protein level whereas increased the levels of Bax and caspase 3 proteins. Moreover, (Ac)(5)GP reduced the degradation and phosphorylation of IκBα, down-regulated NF-κB p65 protein level in nucleus and inhibited NF-κB p65 nuclear translocation. CONCLUSIONS: (Ac)(5)GP had a potent pro-apoptotic effect on AIA FLS in vitro, which is associated with regulating apoptosis-related proteins and inhibiting NF-κB activation.
31088038 Over-Expression of PTEN Suppresses the Proliferation and Migration of Fibroblast-Like Syno 2019 BACKGROUND/AIMS: Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and the subsequent destruction of adjacent articular cartilage and bone. Recent studies have shown that phosphatase and tension homolog deleted on chromosome 10 (PTEN) might contribute to the surviva of fibroblast-like synoviocytes (FLSs) and the production of pro-inflammatory cytokines in RA. The purpose of this study was to explore the functions and underlying mechanisms of PTEN in the proliferation and migration of FLSs. METHODS: FLSs were obtained from adjuvant-induced arthritis (AIA) and normal rats. The expression levels of PTEN, c-Myc, cyclin D1, PCNA, and MMP-9 were detected by quantitative-real-time-PCR and western blot assay. A BrdU proliferation assay, cell cycle analysis, and a wound-healing assay were used to study the role of PTEN in FLSs treated with PTEN inhibitor bpv, specific small interfering RNA targeting PTEN (PTEN-RNAi) or a PTEN over-expression vector (PTEN-GV141). Chromatin immunoprecipitation and methylation-special PCR assays were used to study the expression of PTEN mRNA in the presence of DNA methylation. RESULTS: PTEN expression was downregulated in AIA FLSs in comparison to normal rats. Moreover, inhibition of PTEN expression by bpv or PTEN-RNAi could promote the proliferation and migration of FLSs, and increase the expression of c-Myc, cyclin D1, PCNA, and MMP-9 in AIA FLSs, but had no effect on TIMP-1 expression.In addition, transfection of AIA FLSs with PTEN-GV141 reduced their proliferation and migration. Further study indicated that DNA methylation could regulate PTEN expression in AIA. CONCLUSION: Our findings suggest that PTEN might play a pivotal role in the proliferation and migration of FLSs through the activation of the AKT signaling pathway. Additionally, PTEN expression may be regulated by DNA methylation in the pathogenesis of AIA.
31574126 Correction: Low dose naltrexone: Effects on medication in rheumatoid and seropositive art 2019 [This corrects the article DOI: 10.1371/journal.pone.0212460.].
31732557 Models of Arthritis Care: A Systems-level Evaluation of Acceptability as a Dimension of Qu 2020 Sep 1 OBJECTIVE: To describe a systems-level baseline evaluation of central intake (CI) and triage systems in arthritis care within Alberta, Canada. The specific objectives were to (1) describe a process for systems evaluation for the provision of arthritis care; (2) report the findings of the evaluation for different clinical sites that provide arthritis care; and (3) identify opportunities for improving appropriate and timely access based on the findings of the evaluation. METHODS: The study used a convergent mixed methods design. Surveys and semistructured interviews were the main data collection methods. Participants were recruited through 2 rheumatology clinics and 1 hip and knee clinic providing CI and triage, and included patients, referring physicians, specialists, and clinic staff who experienced CI processes. RESULTS: A total of 237 surveys were completed by patients (n = 169), referring physicians (n = 50), and specialists (n = 18). Interviews (n = 25) with care providers and patients provided insights to the survey data. Over 95% of referring physicians agreed that the current process of CI was satisfactory. Referring physicians and specialists reported issues with the referral process and perceived support in care for wait-listed patients. Patients reported positive experiences with access and navigation of arthritis care services but expressed concerns around communication and receiving minimal support for self-management of their arthritis before and after receiving specialist care. CONCLUSION: This baseline evaluation of CI and triage for arthritis care indicates satisfaction with the service, but areas that require further consideration are referral completion, timely waiting lists, and further supporting patients to self-manage their arthritis.
30604204 Supervised walking improves cardiorespiratory fitness, exercise tolerance, and fatigue in 2019 Feb OBJECTIVE: The aim of this study was to evaluate the safety and effectiveness of a supervised walking program in women with primary Sjögren's syndrome (pSS). METHODS: Forty-five sedentary women fulfilling the American European Consensus Criteria for pSS were randomized to a training group (TG, n = 23) or control group (CG, n = 22). Patients in the TG were submitted to supervise walking three times a week for 16 weeks. The patients of the CG were instructed to not perform any kind of regular physical exercise. Physical fitness [maximum oxygen uptake (VO(2max)) and distance], EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), hematological tests, and Medical Outcomes Study 36 (SF-36) were assessed at baseline and week 16. In addition, EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Functional Assessment of Chronic Illness Therapy Fatigue Subscale (FACIT-fatigue), and Beck Depression Inventory (BDI) were measured prior to intervention, after 8 and 16 weeks. Patient global assessment of response to therapy was completed at the final assessment. An intent-to-treat analysis was performed. RESULTS: After 16 weeks, the mean change of VO(2max) (ml/kg/min), distance, and FACIT-fatigue were higher in the TG than in the CG (p = 0.016, p = 0.043 and p = 0.030, respectively). Improved cardiorespiratory fitness was associated with improvements in fatigue scores and physical components of quality of life (SF-36). Furthermore, improved fatigue scores were associated with reduced depression and improvements in the physical and mental components of SF-36. Overall, 95.4% of patients in the TG rated themselves as clinically improved versus 62% of the patients in the CG (p = 0.049). There was no flare in disease activity and no serious adverse events with exercise. CONCLUSIONS: This supervised walking program was demonstrated to be feasible and safe with improvements in cardiorespiratory fitness, exercise tolerance, fatigue, and patient perception of improvement in pSS patients. TRIAL REGISTRATION: Clinical Trials.gov ID, number NCT02370225.
30086205 Interventions for dry mouth and hyposalivation in Sjögren's syndrome: A systematic review 2019 May OBJECTIVES: Systematic review with meta-analysis of interventions for dry mouth symptoms and hyposalivation of Sjögren's syndrome (SS). MATERIALS AND METHODS: We searched MEDLINE, Cochrane Central and EMBASE up to February 2018 for randomized trials of interventions for dry mouth and hyposalivation of SS. The primary outcome was the mean change in xerostomia symptoms. The secondary outcomes included changes in salivary flow and quality of life. We used the Cochrane risk of bias tool for individual studies and the GRADE method to summarize the quality of evidence across studies for the included outcomes. RESULTS: Thirty-six studies (3,274 patients) were included in the systematic review. Results from the meta-analyses showed high-quality evidence that pilocarpine was superior to placebo in reducing dry mouth symptoms. We found moderate quality of evidence that pilocarpine, rituximab and interferon-alpha were more effective than placebo in increasing salivary flow, with the relevant effect size being large for pilocarpine, and notably smaller for rituximab and interferon-alpha. CONCLUSION: Clinicians should be very confident in the beneficial effects of pilocarpine upon dry mouth symptoms of SS and moderately confident that pilocarpine, rituximab and interferon-alpha can have beneficial effects upon salivary flow. Adverse events are common. The use of other treatment modalities cannot be supported on the basis of current evidence.
31804146 Usefulness of a deep learning system for diagnosing Sjögren's syndrome using ultrasonogra 2020 Mar OBJECTIVES: We evaluated the diagnostic performance of a deep learning system for the detection of Sjögren's syndrome (SjS) in ultrasonography (US) images, and compared it with the performance of inexperienced radiologists. METHODS: 100 patients with a confirmed diagnosis of SjS according to both the Japanese criteria and American-European Consensus Group criteria and 100 non-SjS patients that had a dry mouth and suspected SjS but were definitively diagnosed as non-SjS were enrolled in this study. All the patients underwent US scans of both the parotid glands (PG) and submandibular glands (SMG). The training group consisted of 80 SjS patients and 80 non-SjS patients, whereas the test group consisted of 20 SjS patients and 20 non-SjS patients for deep learning analysis. The performance of the deep learning system for diagnosing SjS from the US images was compared with the diagnoses made by three inexperienced radiologists. RESULTS: The accuracy, sensitivity and specificity of the deep learning system for the PG were 89.5, 90.0 and 89.0%, respectively, and those for the inexperienced radiologists were 76.7, 67.0 and 86.3%, respectively. The deep learning system results for the SMG were 84.0, 81.0 and 87.0%, respectively, and those for the inexperienced radiologists were 72.0, 78.0 and 66.0%, respectively. The AUC for the inexperienced radiologists was significantly different from that of the deep learning system. CONCLUSIONS: The deep learning system had a high diagnostic ability for SjS. This suggests that deep learning could be used for diagnostic support when interpreting US images.
31780281 Discovering new metabolite alterations in primary sjögren's syndrome in urinary and plasm 2020 Feb 5 Sjögren's Syndrome (SjS) is a complex autoimmune disease characterized by the affection of the exocrine glands and the involvement of multiple organs. Although a greater number of biomarker studies have been carried out in recent years, the origin and pathogenesis are not yet well known and therefore there is a need to continue studying this pathology. This work aims to find metabolic changes in biological samples (plasma and urine), which could help identify the metabolic pathways affected by the SjS pathogenesis. The samples collected from SjS patients and healthy volunteers were analyzed by a fingerprinting metabolomic approach based on HPLC-ESI-QTOF-MS methodology. After feature pre-selection by univariate statistical tests, an integrated PLS-DA model using data from urine and plasma was constructed obtaining a good classification between cases and controls (AUROC = 0.839 ± 0.021). 31 and 38 metabolites in plasma and urine, respectively, showed significant differences between healthy volunteers and SjS patients and were proposed for their identification. From them, 12 plasma and 24 urinary metabolites could be annotated. In general, the main metabolic pathways altered in SjS patients were related to the metabolism of phospholipids, fatty acids, and amino acids, specially tryptophan, proline and phenylalanine.
31696913 Sjögren syndrome and MIG. 2019 Nov In the ductal epithelium adjacent to lymphoid infiltrates and in lymphocytes of salivary glands in patients with Sjögren syndrome (SS), there is an increased expression of monokine induced by interferon (IFN)-γ(MIG) and chemokine (C-X-C motif) receptor 3 (CXCR)3, which therefore seems to participate in the SS pathogenesis. Cultured SS salivary epithelial cells treated with IFN-γ release high levels of IFN-γ-inducible protein 10 (IP-10) and MIG. MIG secreted by salivary epithelial cells (under IFN-γ influence), recruits Type-1 helper (Th1) lymphocytes that create an amplification feedback loop, and perpetuates the autoimmune process, through an enhanced IFN-γ induction, that in turn stimulates an additional MIG secretion from epithelial cells. The high levels of MIG in saliva and tears indicate an immune Th1 dependent response. An amelioration of autoimmune sialadenitis with MIG antagonists has been observed in experimental settings, suggesting a possible therapeutic approach to SS. More investigations are needed to assess whether MIG is a novel therapeutic target for SS in humans.
31464680 Salivary extracellular vesicles versus whole saliva: new perspectives for the identificati 2019 May In the era of personalised medicine new biomarkers are required to early diagnose Sjögren's syndrome (SS), to define different disease subsets and to direct patients' clinical management and therapeutic intervention. In the last few years, several efforts have evaluated saliva proteome to detect and monitor primary SS. Although clinically valuable, these studies presented some limitations that have partially prevented the use of salivary biomarkers in clinical practice. Nowadays, proteomic of extracellular vesicle (EV) represents an emerging and promising field in the discovery of -omic biomarkers for pSS. EV is a relatively new term that includes exosomes, microvesicles and apoptotic body. EVs are packed with proteins, growth factors, cytokines, bioactive lipids, but also nucleic acids and in particular: mRNA, microRNA, long non-coding RNA, tRNA and rRNA. Therefore, they may represent a useful source for diagnostic, prognostic and therapeutic biomarkers in several conditions. In this review we will specifically focus on EV proteomics as a tool for the identification of novel biomarkers for pSS. In the first part we focused on the state of the art of the studies on proteomics in SS existing in the literature. In the second part we provided a definition of EV with an update on biological sample collection and processing for EV proteomic studies. Finally, we summarised the state of the art of EV -omics in SS highlighting the potential advantages of this novel approach compared to the overall traditional concept of analysing the proteome of blood or saliva.
31843713 Clinical, morphological features and prognostic factors associated with interstitial lung 2020 Feb OBJECTIVE: To evaluate the prevalence, clinical presentation, serological and morphological features of, and therapeutic options for Interstitial Lung Disease (ILD) in primary Sjögren's Syndrome (pSS). METHODS: Pubmed was searched between February 1996 and December 2018 using a combination of MESH terms related to pSS and ILD. Selected works were subjected to blind evaluation by two authors and a senior author in case of disagreement. The work followed PRISMA guidelines and was registered on PROSPERO (CRD42018118669). RESULTS: About 20% of pSS patients have ILD, with a 5-y survival of 84% and a need for supplemental oxygen in the 11-33% range. A significant proportion of ILD patients are seronegative without sicca syndrome. ILD seems to be associated with higher levels of Lactic Dehydrogenases and positivity for Anti-Ro52k. The prevalent pattern in High Resolution Computed Tomography is Nonspecific Interstitial Pneumonia (NSIP), but all other patterns can be present. No difference in mortality was found between patients with NSIP and Usual Interstitial Pneumonia patterns. Amyloidosis and primary lung lymphoma can be observed in about 10% of pSS patients. CONCLUSION: The recognition of pSS underlying an ILD can be challenging in seronegative patients with no or mild sicca symptoms. A complete diagnostic assessment, including minor salivary glands and, in some cases, lung biopsy, should be performed on all patients at risk. A better recognition of the clinical or serological markers of ILD progression in these patients is warranted to drive the physicians to an early diagnosis and an effective treatment.
30793563 [Congenital heart block revealing a maternal systemic disease : pathophysiology and therap 2019 Feb Immunologic congenital atrioventricular block is due to the presence of anti-SSA and anti-SSB antibodies in maternal blood. This pathology is often diagnosed when the status is irreversible and is consequently associated with a high morbi-mortality. Close monitoring for high risk pregnancies can help to diagnose first and second degrees heart block and treatments can be offered when the block is still reversible. Fluorocorticoids, betamimetics and hydroxychloroquine use is not consensual. Studies are still in progress to prove their utility. We report the antenatal managing of a patient in which Goujerot-Sjögren disease was diagnosed after the revealing of an atrioventricular block in her fetus. After a brief physiopathological description, we present the current knowledge in preventive and curative treatments.
30371536 Mucosal-associated Lymphoid Tissue (MALT) Lymphoma in Association With Pediatric Primary S 2019 Jul Mucosal-associated lymphoid tissue (MALT) lymphoma is rare in the pediatric population, but primary Sjogren syndrome is a well-established risk factor for this malignancy. This report describes 2 cases of MALT lymphoma in children with Sjogren syndrome. A 15-year-old girl developed MALT lymphoma of the parotid gland as the presenting symptom of Sjogren syndrome. In the second case, a 15-year-old boy with known Sjogren syndrome presenting mainly with arthritis was diagnosed with MALT lymphoma, also of the parotid gland. With early diagnosis and treatment, outcomes in pediatric MALT lymphoma are generally encouraging. Pediatric oncology specialists should be aware of the association of MALT lymphoma with Sjogren syndrome and have a high index of suspicion for this malignant complication.
30700425 Porphyromonas gingivalis experimentally induces periodontis and an anti-CCP2-associated ar 2019 May OBJECTIVES: Association between periodontal disease (PD) and rheumatoid arthritis (RA) has been extensively described, but direct evidence of causal involvement of PD in RA is missing. We investigated the priming role of oral Porphyromonas gingivalis (P. gingivalis) in PD and subsequent RA and we assessed biomarkers of bone resorption and arthritis development in rats. METHODS: Lewis rats were orally exposed to either P. gingivalis, Prevotella intermedia or control gel for 1 month and then followed for 8 months. The onset and development of PD was assessed by serology, gingivitis severity and micro-CT (µCT). We investigated arthritis development using circulating proinflammatory markers, anticyclic citrullinated peptide (CCP), anticitrullinated protein antibody (ACPA), ankle histology and µCT. RESULTS: PD was only observed in the P. gingivalis treated rats, as early as 1 month postexposure. Joint and systemic inflammation were detected only in the P. gingivalis group after 4 and 8 months. At 8 months, inflammatory cell infiltrate was observed in ankle joints and paralleled cortical erosions and overall cortical bone reduction. Furthermore, anti-CCP2 correlated with local and systemic bone loss. CONCLUSIONS: In our long-term study, PD induced by oral exposure to P. gingivalis triggered seropositive arthritis, with systemic inflammation and bone erosions. This is the first in vivo demonstration of arthritis induced by oral priming with P. gingivalis.
31508727 Diagnostic potential of saliva proteome analysis: a review and guide to clinical practice. 2019 Proteomic techniques have become popular in medicine and dentistry because of their widespread use in analyzing bodily fluids such as blood, saliva, urine, and gingival crevicular fluids as well as hard tissues such as enamel, dentine, and cementum. This review is a guide to proteomic techniques in general dentistry, summarizing techniques and their clinical application in understanding and diagnosing diseases and their use in identifying biomarkers of various diseases.