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ID PMID Title PublicationDate abstract
29898764 Anti-carbamylated protein antibodies as a new biomarker of erosive joint damage in systemi 2018 Jun 14 BACKGROUND: The application of more sensitive imaging techniques, such as ultrasonography (US), changed the concept of non-erosive arthritis in systemic lupus erythematosus (SLE), underlining the need for biomarkers to identify patients developing the erosive phenotype. Anti-citrullinated peptide antibodies (ACPA), associated with erosions in inflammatory arthritis, have been identified in about 50% of patients with SLE with erosive arthritis. More recently, anti-carbamylated proteins antibodies (anti-CarP) have been associated with erosive damage in rheumatoid arthritis. We aimed to assess the association between anti-CarP and erosive damage in a large SLE cohort with joint involvement. METHODS: We evaluated 152 patients (male/female patients 11/141; median age 46 years, IQR 16; median disease duration 108 months, IQR 168). All patients underwent blood draw to detect rheumatoid factor (RF) and ACPA (commercial enzyme-linked immunosorbent assay (ELISA) kit), and anti-CarP ("home-made" ELISA, cutoff 340 aU/mL). The bone surfaces of the metacarpophalangeal and proximal interphalangeal joints were assessed by US: the presence of erosions was registered as a dichotomous value (0/1), obtaining a total score (0-20). RESULTS: The prevalence of anti-CarP was 28.3%, similar to RF (27.6%) and significantly higher than ACPA (11.2%, p = 0.003). Erosive arthritis was identified in 25.6% of patients: this phenotype was significantly associated with anti-CarP (p = 0.004). Significant correlation between anti-CarP titer and US erosive score was observed (r = 0.2, p = 0.01). CONCLUSIONS: Significant association was identified between anti-CarP and erosive damage in SLE-related arthritis, in terms of frequency and severity, suggesting that these antibodies can represent a biomarker of severity in patients with SLE with joint involvement.
29749546 Serum proteomic analysis of the anti‑arthritic effects of sinomenine on rats with collag 2018 Jul Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized by inflammatory synovitis, and the subsequent destruction of articular cartilage and bone. Sinomenine is a traditional Chinese medicine, which has been employed as a clinical treatment for RA for several years in China. The present study investigated the anti‑arthritic effects of sinomenine on Sprague‑Dawley rats with collagen‑induced arthritis (CIA). The differentially expressed proteins in serum were measured by proteomic analysis in order to generate a differentially expressed protein network. A total of 320 differentially expressed proteins were detected in the drug‑treated group compared with in the control group. In the sinomenine‑treated group, 79 differentially expressed proteins were detected compared with in the model group, and among these, 46 proteins were upregulated. Gene ontology analysis revealed that five functions were affected by sinomenine treatment of CIA rats compared with in the model group. In addition, Ingenuity® Pathway Analysis was used to measure enriched signaling pathways, which revealed nuclear factor‑κB, histones, heat shock proteins and protein kinase B as core proteins, generating ~60 pair associations in the network. To the best of our knowledge, the present study is the first to perform proteomic analysis in sinomenine‑treated CIA rats, and the results revealed that numerous targets were involved in the process. In addition, the present study provided a novel approach and evidence for exploring the biological effects of sinomenine. Therefore, the findings of the present study may provide a novel insight into the anti‑RA mechanisms of sinomenine, and may justify further exploration into its function in other relevant diseases.
30328647 The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue and Immune Responses in Pati 2019 Jul OBJECTIVES: Primary Sjögren's syndrome (pSS) sufferers have rated chronic fatigue as the most important symptom needing improvement. Emerging data suggest that stimulation of the vagus nerve can modulate immunological responses. The gammaCore device (electroCore), developed to stimulate the cervical vagus nerve noninvasively, was used to assess the effects of vagus nerve activation on immune responses and clinical symptoms of pSS. MATERIALS AND METHODS: Fifteen female pSS subjects used the nVNS device twice daily a 26-day period. At baseline, blood was drawn before and after application of the gammaCore device for 90 sec over each carotid artery. The following fatigue-related outcome measures were collected at baseline, day 7 and day 28: EULAR patient reported outcome index, profile of fatigue (Pro-F), visual analogue scale of abnormal fatigue, and Epworth sleepiness scale (ESS). Whole blood samples were stimulated with 2 ng/mL lipopolysaccharide (LPS) and the supernatant levels of IFNγ, IL12-p70, TNFα, MIP-1α, IFNα, IL-10, IL-1β, IL-6, and IP-10 were measured at 24 hours. In addition, clinical hematology and flow cytometric profiles of whole blood immune cells were analyzed. RESULTS: Pro-F and ESS scores were significantly reduced across all three visits. LPS-stimulated production of IL-6, IL-1β, IP-10, MIP-1α, and TNFα were significantly reduced over the study period. Patterns of NK- and T-cell subsets also altered significantly over the study period. Interestingly, lymphocyte counts at baseline visit correlated to the reduction in fatigue score. CONCLUSION: The vagus nerve may play a role in the regulation of fatigue and immune responses in pSS and nVNS may reduce clinical symptoms of fatigue and sleepiness. However, a sham-controlled follow-up study with a larger sample size is required to confirm the findings.
29604186 Clinical Efficacy and Safety of Baminercept, a Lymphotoxin β Receptor Fusion Protein, in 2018 Sep OBJECTIVE: To evaluate the clinical efficacy and safety of baminercept, a lymphotoxin β receptor IgG fusion protein (LTβR-Ig), for the treatment of primary Sjögren's syndrome (SS), and to explore the possible mechanisms of action of this treatment. METHODS: In this multicenter trial, 52 patients with primary SS were randomized in a 2:1 ratio to receive subcutaneous injections of 100 mg of baminercept every week for 24 weeks or matching placebo. The primary end point was the change between screening and week 24 in the stimulated whole salivary flow (SWSF) rate. Secondary end points included the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI), as well as measurements of select chemokines and cytokines and enumeration of peripheral blood B and T cell subsets. RESULTS: The change from baseline to week 24 in the SWSF rate was not significantly different between the baminercept and placebo treatment groups (baseline-adjusted mean change -0.01 versus 0.07 ml/minute; P = 0.332). The change in the ESSDAI during treatment was also not significantly different between the treatment groups (baseline-adjusted mean change -1.23 versus -0.15; P = 0.104). Although the incidence of adverse events was similar between the treatment groups, baminercept therapy was associated with a higher incidence of liver toxicity, including 2 serious adverse events. Baminercept also produced a significant decrease in plasma levels of CXCL13 and significant changes in the number of circulating B and T cells, consistent with its known inhibitory effects on LTβR signaling. CONCLUSION: In this trial, treatment with baminercept failed to significantly improve glandular and extraglandular disease in patients with primary SS, despite evidence from mechanistic studies showing that it blocks LTβR signaling.
28421999 Use and withdrawal of immunosuppressors in primary Sjögren's syndrome. 2018 May OBJECTIVES: To assess the use and causes of withdrawal of glucocorticoids and immunosuppressors among patients with primary Sjögren's syndrome (pSS) in the clinical setting. METHODS: We retrospectively reviewed the medical records of 155 pSS patients and registered demographics, glandular/extraglandular features, serological data, cumulative ESSDAI and SSDDI. A single rheumatologist attributed the indication and cause of withdrawal of glucocorticoids and immunosuppressors. RESULTS: 92.2% of the patients were female, mean age 57.4±14.7 years and median follow-up 11 years. One hundred and four (67%) patients received glucocorticoids and/or immunosuppressors: 3.8% only glucocorticoids, 43.9% only immunosuppressors and 56.5% their combination. The most used drugs were antimalarials (46.4%), prednisone (36.7%), azathioprine (AZA) (23.8%) and methotrexate (MTX) (18%). At the multivariate analysis, the presence of non-erosive arthritis OR 5.02 (95% CI 1.74-14.47, p=0.003) and the median cumulative ESSDAI score OR 1.10 (95% CI 1.03-1.17, p=0.002) were associated with the use of these drugs. The causes of withdrawal were: 39% improvement, 35.2% patient's own decision, 18.1% toxicity and 11% lack of efficacy. We found toxicity in 14.2% MTX users, 9.7% for AZA, 9.7% for antimalarials and 7.6% for cyclophosphamide. CONCLUSIONS: More than half the patients received glucocorticoids and/or immunosuppressors and a not negligible number decided on their own to suspend them, alerting physicians of secondary adverse events and tolerability.
30156550 The role of salivary gland histopathology in primary Sjögren's syndrome: promises and pit 2018 May The formation of lymphomononuclear cell infiltrates organising as periductal infiltrates in the salivary glands of patients with primary Sjögren's syndrome (pSS) is one of the hallmarks of the disease. Historically, the clinical role of salivary gland histopathology, most commonly performed on labial salivary gland biopsies, has been confined to the clinical classification and diagnosis of pSS whereby according to the ACR-EULAR a positive histopathology finding is a requirement for the diagnosis of pSS in the absence of anti-Ro/SSA antibodies. In recent years, further understanding of the heterogeneity of the immune cell infiltration and organisation within the salivary glands of pSS patients and its correlation with clinical manifestations of the disease has led to propose salivary gland histopathology as a novel tool able to identify patients at higher risk of developing more severe extraglandular manifestations and lymphoma. Furthermore, recent clinical developments in ongoing randomised clinical trials with novel biologics in pSS have focused on salivary glands histopathology to inform on patients stratification based on target validation, proof of drug efficacy and mechanisms of response/resistance to therapy. However, lack of standardisation of methodology and analysis has hindered the reproducibility of data from different groups and no definitive evidence in support of the use of salivary glands histopathology to inform clinical management of patients with pSS has been provided. In this review, we summarise recent evidence highlighting the promises and pitfalls of salivary glands histopathology in pSS emphasising the need for an international consensus on standardisation of methodology with validation in large prospective multicentre initiatives.
29610453 Sjögren's Syndrome Associated with Fanconi's Syndrome and Osteomalacia. 2018 Apr 3 BACKGROUND Sjögren's syndrome is a chronic inflammatory autoimmune disease, which is also known as sicca syndrome, due to the symptoms of dry eyes and dry mouth, and is associated with other connective tissue diseases and autoimmune diseases. Sjögren's syndrome can also be associated with renal involvement. Fanconi's syndrome is associated with impaired reabsorption in the proximal renal tubule associated with tubulointerstitial nephritis and is associated with renal tubular acidosis and hypophosphatemia. Osteomalacia is a rare association with Sjögren's syndrome, which may result from renal disease. CASE REPORT We report the case of a 34-year-old woman who presented with xerostomia, xerophthalmia, bone fractures, and osteomuscular pain. A Schirmer test showed reduced tear production, and a biopsy of a minor salivary gland of the lip, with high titers of antinuclear antibodies (ANA), and positive anti-SSA/Ro and anti-SSB/La antibodies confirmed the diagnosis of Sjögren's syndrome. Serum and urinary laboratories tests and clinical manifestations confirmed Fanconi's syndrome associated with osteomalacia. The patient was treated with potassium supplements, 25-hydroxyvitamin D (25(OH)D), hydroxychloroquine, mycophenolate mofetil, and prednisone, with a favorable response. CONCLUSIONS This case is of a rare association between Sjögren's syndrome, Fanconi's syndrome, and osteomalacia. Even though these are rare clinical associations, early detection can improve the quality of life and prevent further complications.
29607915 [A case of limbic encephalitis associated with Sjögren's syndrome mimicking anti N-methyl 2018 Apr 25 A 25-year-old woman in her 37 weeks and 5 days pregnant presented with abnormal behavior and memory impairment following a high fever. Her manifestations were diagnosed as limbic encephalitis, and she delivered a baby by Cesarean section. In the operation, bilateral ovarian tumors were found and resected, though they were revealed as non-teratoma afterward. After operation, she became agitated, and started to present oral dyskinesia, intractable systemic myoclonus, central hypoventilation, and autonomic manifestations such as labile blood pressure, but her symptoms responded well to immunotherapy. Her clinical course was typical for anti-N-methyl D-aspartate (NMDA) receptor encephalitis, but anti-NMDA receptor antibody was not detected in her serum and CSF. On the other hand, anti SS-A antibody was positive in her serum, and the lip biopsy findings confirmed Sjögren's syndrome (SjS). Only several cases of SjS-associated limbic encephalitis have been reported, but none of them mimicked anti-NMDA receptor encephalitis. This patient indicates that SjS should be considered even in a case of limbic encephalitis with a typical clinical spectrum of anti-NMDAR encephalitis.
30018954 Synovial Predictors of Differentiation to Definite Arthritis in Patients With Seronegative 2018 Objectives: To examine synovial tissue (ST) predictors of clinical differentiation in patients with seronegative undifferentiated peripheral inflammatory arthritis (UPIA). Methods: Fourty-two patients with IgA/IgM-Rheumatoid Factor and anti-citrullinated peptide antibodies negative UPIA, naive to Disease-Modifying Anti-Rheumatic Drugs, underwent Gray Scale (GSUS) and power Doppler (PDUS) evaluation and Ultrasound (US) guided ST biopsy. CD68, CD3, CD21, CD20, and CD31 synovial expression was evaluated by immunohistochemistry. Whole ST microRNA expression was assessed using miScript miRNA PCR Array. Peripheral blood (PB) and synovial fluid (SF) IL-6, VEGF-A, and VEGF-D levels were measured by ELISA and ST TNF expression was assessed by RT-PCR. Each patient was prospectively monitored and classified at baseline and within 1 year as UPIA, Rheumatoid Arthritis (RA), Spondyloarthritis (SpA) or Psoriatic Arthritis (PsA), respectively. Results: At baseline, CD68(+) cells were the most common cells within the lining layer (p < 0.001) in seronegative UPIA, directly correlating with GSUS (R = 0.36; p = 0.02) and PDUS (R = 0.55; p < 0.001). Synovial CD31(+) vessels count directly correlated with GSUS (R = 0.41; p = 0.01) and PDUS (R = 0.52; p < 0.001). During the follow-up, 6 (14.3%) UPIA reached a definite diagnosis (2 RA, 2 SpA and 2 PsA, respectively). At baseline, UPIA who differentiated had higher GSUS (p = 0.01), PDUS scores (p = 0.02) and higher histological scores for CD68(+) (p = 0.005 and p = 0.04 for lining and sublining respectively), sublining CD3(+) cells (p = 0.002), CD31(+) vessels count (p < 0.001) and higher IL-6 PB levels (p = 0.01) than patients who remained as UPIA. MiRNA PCR Array showed that among the 86 tested miRNA species, at baseline, miR-346 and miR-214 were significantly down-regulated (p = 0.02 for both) in ST of UPIA who differentiated than in patients who remained as UPIA, inversely correlating with the lining CD68(+) cells IHC score (R = -0.641; p = 0.048) and CD31(+) vessels count (R = -0.665; p = 0.036) and with higher baseline ST expression of TNF (p = 0.014). Finally, logistic regression analysis demonstrated that baseline GSUS and PDUS scores ≥1.5 [OR:22.93 (95%CI:0.98-534.30)] and CD31(+) vessels count ≥24.3 [OR:23.66 (95%CI:1.50-373.02)] were independent factors associated with the development of definite arthritis. Conclusions: MiRNA signature, histological and US features of ST may help in the identification of seronegative UPIA with high likelihood of clinical differentiation toward definite seronegative arthritis.
30244469 Bone Resorption Activity in Mature Osteoclasts. 2018 Bone homeostasis depends on balanced bone deposition and bone resorption, which are mediated by osteoblasts and osteoclasts, respectively. As one therapeutic strategy, the blockage of osteoclast activity reduces subsequent bone erosion. Morphological analysis of bone resorption pits formed by osteoclasts by using scanning electron microscope is an effective method for understanding rheumatoid arthritis. Here we describe methods for observing surface microstructure of pits formed by osteoclasts on hard tissue sections.
29950544 [Body weight and bone/calcium metabolism. Muscle, myokines and bone/calcium metabolism.]. 2018 The interactions between skeletal muscle and bone have been noted, and muscle influences bone metabolism by secreting myokines. Myostatin is known as a myostatic factor through an inhibition of Smad2/3 signaling in muscle. It is involved in the pathophysiology of rheumatoid arthritis via a stimulation of bone resorption. Follistatin might be involved in the regulation of muscle and bone by gravity change through an attenuation of myostatin action. Irisin with energy metabolism improvement actions is related to the effects of mechanical stress or exercise on muscle and bone. The research of myokines might lead to the improvement of clinical practice of sarcopenia and osteoporosis.
30450819 Prevalence of minimal disease activity in Australian patients with Psoriatic Arthritis: As 2019 Feb AIM: Discrepancies exist between international treatment guidelines and current Australian Pharmaceutical Benefits Scheme (PBS) criteria for funding biologic disease-modifying antirheumatic drug (bDMARD) prescribing in psoriatic arthritis (PsA). We aimed to determine the prevalence of minimal disease activity (MDA) achievement and differences in inflammatory marker levels between PsA patients who have and have not met the Australian PBS criteria for bDMARDs. METHOD: Consecutive participants diagnosed with PsA were assessed for MDA components and serum inflammatory markers. For those on bDMARDs, joint counts and inflammatory markers at the time of bDMARD qualification were compared with matched rheumatoid arthritis (RA) controls. RESULTS: Minimal disease activity was achieved by 56/105 participants overall. There were no differences in inflammatory marker levels or involved joint count patterns between the PsA and RA groups at the time of bDMARD qualification. Seventy-three percent of the 53 PsA patients on bDMARD achieved MDA, vs 33% in the non-bDMARD group (P < 0.001). More bDMARD than non-bDMARD patients achieved four out of seven MDA components. Of those with any enthesitis, its prevalence was higher in the non-bDMARD group (22 vs 10, P = 0.009). Regardless of treatment, there was no difference in inflammatory marker levels between those who did and did not achieve MDA. CONCLUSION: The Australian PBS criteria, funding bDMARD prescribing for PsA, select well for MDA achievers. A high prevalence of MDA non-achievement remains in patients ineligible for bDMARD funding, and enthesitis in this population is more common. Inflammatory markers were not discriminators between treatment or MDA achievement groups.
29295810 Physical Activity Assessment Using an Activity Tracker in Patients with Rheumatoid Arthrit 2018 Jan 2 BACKGROUND: Physical activity can be tracked using mobile devices and is recommended in rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) management. The World Health Organization (WHO) recommends at least 150 min per week of moderate to vigorous physical activity (MVPA). OBJECTIVE: The objectives of this study were to assess and compare physical activity and its patterns in patients with RA and axSpA using an activity tracker and to assess the feasibility of mobile devices in this population. METHODS: This multicentric prospective observational study (ActConnect) included patients who had definite RA or axSpA, and a smartphone. Physical activity was assessed over 3 months using a mobile activity tracker, recording the number of steps per minute. The number of patients reaching the WHO recommendations was calculated. RA and axSpA were compared, using linear mixed models, for number of steps, proportion of morning steps, duration of total activity, and MVPA. Physical activity trajectories were identified using the K-means method, and factors related to the low activity trajectory were explored by logistic regression. Acceptability was assessed by the mean number of days the tracker was worn over the 3 months (ie, adherence), the percentage of wearing time, and by an acceptability questionnaire. RESULTS: A total of 157 patients (83 RA and 74 axSpA) were analyzed; 36.3% (57/157) patients were males, and their mean age was 46 (standard deviation [SD] 12) years and mean disease duration was 11 (SD 9) years. RA and axSpA patients had similar physical activity levels of 16 (SD 11) and 15 (SD 12) min per day of MVPA (P=.80), respectively. Only 27.4% (43/157) patients reached the recommendations with a mean MVPA of 106 (SD 77) min per week. The following three trajectories were identified with constant activity: low (54.1% [85/157] of patients), moderate (42.7% [67/157] of patients), and high (3.2% [5/157] of patients) levels of MVPA. A higher body mass index was significantly related to less physical activity (odds ratio 1.12, 95% CI 1.11-1.14). The activity trackers were worn during a mean of 79 (SD 17) days over the 90 days follow-up. Overall, patients considered the use of the tracker very acceptable, with a mean score of 8 out 10. CONCLUSIONS: Patients with RA and axSpA performed insufficient physical activity with similar levels in both groups, despite the differences between the 2 diseases. Activity trackers allow longitudinal assessment of physical activity in these patients. The good adherence to this study and the good acceptability of wearing activity trackers confirmed the feasibility of the use of a mobile activity tracker in patients with rheumatic diseases.
30886985 A proteomic analysis of serum-derived exosomes in rheumatoid arthritis. 2018 BACKGROUND: To understand the roles of serum exosomes in rheumatoid arthritis (RA), we comprehensively investigated the protein profiles of serum exosomes in patients with RA. METHODS: Exosomes were isolated from serum samples obtained from 33 patients (12 with active RA [aRA], 11 with inactive RA [iRA], 10 with osteoarthritis [OA]) and 10 healthy donors (HLs). Proteins extracted from the exosomes were separated by two-dimensional differential gel electrophoresis (2D-DIGE) and identified by mass spectrometry. RESULTS: In total, 204 protein spots were detected by 2D-DIGE. In the aRA, iRA, and OA groups, 24, 5, and 7 spots showed approximately ≥ ±1.3-fold intensity differences compared with the HL group, respectively. We were able to identify proteins in six protein spots. Among them, the protein spot identified as Toll-like receptor 3 (TLR3) showed approximately 6-fold higher intensity in the aRA group than in the other groups. CONCLUSIONS: Patients with active RA possessed considerably different protein profiles of serum exosomes from patients with iRA, patients with OA, and healthy donors. The unique protein profile of serum exosomes, such as the possession of abundant TLR3 fragments, may reflect the pathophysiology of active RA.
30513848 Prevalence and Fracture Risk of Osteoporosis in Patients with Rheumatoid Arthritis: A Mult 2018 Dec 2 (1) Background: We evaluated the prevalence and fracture risk of osteoporosis in patients with rheumatoid arthritis (RA), and compared the fracture risk assessment tool (FRAX) criteria and bone mineral density (BMD) criteria established by the World Health Organization (WHO). (2) Methods: This retrospective cross-sectional study, which included 479 RA patients in 5 hospitals, was conducted between January 2012 and December 2016. The FRAX criteria for high-risk osteoporotic fractures were calculated including and excluding the BMD values, respectively. The definition of high risk for fracture by FRAX criteria and BMD criteria by WHO was 10-year probability of ≥ 20% for major osteoporotic fracture or ≥ 3% for hip fracture, and T score ≤ -2.5 or Z score ≤ -2.0, respectively. (3) Results: The mean age was 61.7 ± 11.9 years. The study included 426 female patients (88.9%), 353 (82.9%) of whom were postmenopausal. Osteoporotic fractures were detected in 81 (16.9%) patients. The numbers of candidates for pharmacological intervention using the FRAX criteria with and without BMD and the WHO criteria were 226 (47.2%), 292 (61%), and 160 (33.4%), respectively. Only 69.2%⁻77% of the patients in the high-risk group using the FRAX criteria were receiving osteoporosis treatments. The following were significant using the WHO criteria: female (OR 3.55, 95% CI 1.46⁻8.63), age (OR 1.1, 95% CI 1.08⁻1.13), and BMI (OR 0.8, 95% CI 0.75⁻0.87). Glucocorticoid dose (OR 1.09, 95% CI 1.01⁻1.17), age (OR 1.09, 95% CI 1.06⁻1.12), and disease duration (OR 1.01, 95% CI 1⁻1.01) were independent risk factors for fracture. (4) Conclusions: The proportion of RA patients with a high risk of osteoporotic fractures was 33.4%⁻61%. Only 69.2%⁻77% of candidate patients were receiving osteoporotic treatments while applying FRAX criteria. Independent risk factors for osteoporotic fractures in RA patients were age, the dose of glucocorticoid, and disease duration.
29956284 Establishment of a Modified Collagen-Induced Arthritis Mouse Model to Investigate the Anti 2018 Progranulin (PGRN) was found to play an anti-inflammatory and protective role in both inflammatory and degenerative arthritis (Tang et al., Science 332:478-484, 2011; Zhao et al., Ann Rheum Dis 74:2244-2253, 2015). We recently published a visualized protocol to demonstrate a surgically-induced mouse model for examining the protective role of PGRN in degenerative osteoarthritis (Zhao et al., J Vis Exp:e50924, 2014). Herein we describe a modified collagen-induced arthritis (CIA) mouse model to investigate the anti-inflammatory activity of PGRN in inflammatory arthritis. CIA model is the most commonly used autoimmune model of inflammatory arthritis which shares both immunological and pathological features with human rheumatoid arthritis. Autoimmune inflammatory arthritis is induced by immunization with an emulsion of complete Freund's adjuvant and chicken type II collagen (CII) using a modified procedure in PGRN deficient mice and control littermates. Using the protocol described here, the investigator should be able to reproducibly induce a high incidence of CIA in PGRN deficient mice and also learn how to critically evaluate the severity and incidence of this disease model.
29208331 Autoimmune and medication-induced lymphadenopathies. 2018 Jan This article will provide a discussion of some common autoimmune disorders that could affect the lymph nodes and potentially mimic B and T-cell lymphomas. Some of these disorders are more characteristic of individuals in the pediatric age group (autoimmune lymphoproliferative syndrome, Kawasaki disease), while others present in older individuals (rheumatoid arthritis, lupus erythematosus, sarcoidosis). A common finding that groups all of these disorders together is the overall relative preservation of the architecture, a feature that can be particularly helpful to distinguish them from many B and T-cell lymphomas. Another area of interest, that will be discussed in this review, is the pathologic manifestations that can be present in lymph nodes secondary to medications. Such alterations range from 'reactive' forms of follicular, interfollicular or paracortical hyperplasia, to specific B and T-cell lymphoproliferative disorders (particularly documented in association with methotrexate and TNF-inhibitors).
29030294 Type I interferon pathway activation in COPA syndrome. 2018 Feb Mutations of the COPA gene cause an immune dysregulatory disease characterised by polyarticular arthritis and progressive interstitial lung disease with pulmonary haemorrhages. We report the case of a young girl that presented at age 3 with polyarticular arthritis, chronic cough and high titer rheumatoid factor. Radiologic imaging showed interstitial lung disease with tree-in-a-bud nodules and air-filled cysts. Targeted genetic analysis of COPA gene showed the reported c.698G>A mutation. The patient was lost to follow up for 3years during which therapy was discontinued with the development of joint damage and deformities. Analysis of peripheral blood showed activation of type 1 interferon pathway, which was also confirmed in 4 previously reported COPA patients. Our observations underline the importance of early treatment in COPA disease to avoid loss of joint function. Furthermore, our results suggest a role for type 1 interferon in disease pathogenesis opening the possibility for targeted therapeutic approaches.
28782470 Novel Insights into the Pathogenesis of Osteoarthritis. 2018 Osteoarthritis represents the most frequently diagnosed condition of the musculoskeletal system and accounts for a high amount of direct and indirect socioeconomic costs worldwide. While for rheumatoid arthritis much progress has been made in the past decades both in understanding its pathogenesis and in creating novel therapies, the pathophysiology of osteoarthritis still holds several secrets to be unraveled in the near future in order to also allow for the development of effective novel pharmacotherapeutical options. Though first categorized as a joint disorder being primarily non-inflammatory in nature for a long period of time with research focused on biomechanic aspects and imbalanced wear and tear, recent evidence including immunological processes helped to refine disease interpretation. Thus, showing true inflammatory characteristics that clinically emerge as synovitis, osteoarthritis is nowadays recognized to include signs of inflammation that at least histologically may sometimes be indistinguishable from rheumatoid synovial infiltration. Although this was known already more than 25 years ago, efforts made in solving pathophysiologic key issues did not succeed sufficiently. This review is thought to summarize elementary pathogenic aspects including genetic predisposition and epigenetic regulation and highlights important central innate but also putative adaptive immunological mechanisms today generally accepted to drive inflammation and tissue destruction in osteoarthritis.
30403265 Association between systemic activity ındex and dry eye severity in patients with primary 2019 Jan PURPOSE: The aim of the present study was to compare the severity of ocular and systemic findings among patients with primary Sjögren syndrome. METHODS: The study followed a prospective controlled design and comprised two groups; the test group included 58 eyes of 58 patients newly diagnosed with primary Sjögren syndrome with poor dry eye test findings and the control group included 45 right eyes of 45 healthy age- and sex-matched individuals. The ocular surface disease index score, tear osmolarity, Schirmer I test without anesthesia, fluorescein tear breakup time, and cornea-conjunctiva staining with lissamine green (van Bijsterveld scoring) were used to examine tear function in the patients via a complete ophthalmological examination. The results were graded and classified on the basis of a Dry Eye WorkShop report and results of the corneal and conjunctival staining test, Schirmer's test, and fluorescein tear breakup time test. Discomfort, severity and frequency of symptoms, visual symptoms, conjunctival injection, eyelid-meibomian gland findings, and corneal-tear signs were interpreted. Disease activity was scored per the EULAR Sjögren's syndrome disease activity index (ESSDAI) via systemic examination and laboratory evaluations, and the EULAR Sjögren's syndrome patient-reported index (ESSPRI) assessed via a survey of patient responses. RESULTS: Mean patient age was 48.15 ± 16.34 years in the primary Sjögren syndrome group and 44.06 ± 9.15 years in the control group. Mean fluorescein tear breakup time was 4.51 ± 2.89s in the primary Sjögren syndrome group and 10.20 ± 2.39 s in the control group. Mean Schirmer I test result was 3.51 ± 3.18 mm/5 min in the primary Sjögren syndrome group and 9.77±2.30 mm/5 min in the control group. Mean ocular surface disease index score was 18.56 ± 16.09 in the primary Sjögren syndrome group, and 19.92 ± 7.16 in the control group. Mean osmolarity was 306.48 ± 19.35 in the primary Sjögren syndrome group, and 292.54 ± 10.67 in the control group. Mean lissamine green staining score was 2.17 ± 2.76 in the primary Sjögren syndrome group, and 0.00 in the control group. Statistically significant differences were found berween the primary Sjögren syndrome group and control group in terms of fluorescein tear breakup time, Schirmer's test, lissamine green staining, and osmolarity tests (p=0.036, p=0.041, p=0.001, and p=0.001 respectively). The Dry Eye WorkShop score was 2.15 ± 0.98, the EULAR Sjögren's syndrome disease activity index score was 11.18 ± 4.05, and the EULAR Sjögren's syndrome patient-reported index score was 5.20±2.63. When potential associations of the Dry Eye Workshop Study scores and osmolarity scores with the Eular Sjögren's syndrome disease activity index scores were evaluated, the results were found to be statistically significant (p=0.001, p=0.001 respectively). CONCLUSION: The results showed an association between dry eye severity and systemic activity index in primary Sjögren syndrome patients.