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ID PMID Title PublicationDate abstract
30266125 Fibromodulin: Structure, Physiological Functions, and an Emphasis on its Potential Clinica 2018 Oct Fibromodulin (FMOD) is one of the small leucine-rich proteoglycans. A search of the literature did not reveal any paper that specifically reviews the potential clinical applications of FMOD in the management of human diseases. First, the structure and physiological functions of FMOD were reviewed. Then its potential clinical applications in various diseases including diseases of the skin, tendons, joints, intervertebral discs, blood vessels, teeth, uterus, bone and kidney were reviewed. FMOD is able to switch the adult response to skin wounding to the desired fetal response of scarless healing. Lowered levels of FMOD would be desirable in the management of tendinopathy, uterine fibroids, tumors resistant to radiotherapy, glioblastomas, small-cell lung cancer, and primary liver/lung fibrosis. In contrast, increased levels of FMOD would be desirable in the management of acute tendon injuries, osteoarthritis, rheumatoid arthritis, temporo-mandibular disease, joint laxity, intervertebral disc disease, neo-intimal hyperplasia of vein grafts, teeth caries, periodontal disease, endometrial atrophy, osteoporosis and diabetic nephropathy. Furthermore, FMOD may be used as a prognostic marker of cerebrovascular events in patients undergoing carotid endarterectomy and a marker for prostatic cancer. Finally, the use of FMOD in the treatment of symptomatic endometrial atrophy should be explored in women who are unable to use the standard estrogen management for endometrial atrophy. The review concluded that clinical trials in humans should be initiated to investigate the potential therapeutic effects of FMOD.
30176059 Simultaneous determination of tiopronin and its primary metabolite in plasma and ocular ti 2019 Feb Tiopronin, formally 2-mercaptopropionylglycine (MPG), is currently prescribed to treat cystinuria and rheumatoid arthritis, and its antioxidant properties have led to its investigation as a treatment for cataracts, a condition in which oxidative stress is strongly implicated. To study its accumulation in the eye, a reliable, isocratic HPLC method was developed for the determination of MPG and its primary metabolite 2-mercaptopropionic acid (MPA) in plasma and relevant ocular tissues. This method utilizes pre-column derivatization and fluorescence detection. The 3.5 min separation enables high-throughput analysis, and validation experiments demonstrated that this method is suitable for evaluating ocular accumulation of MPG and MPA at concentrations as low as 66 and 33 nm, respectively. Excellent linearity was achieved over the working concentration range with R(2)  > 0.997. Extraction recovery was reproducible within each matrix and exceeded 97%. Accuracy was within 13.3% relative error, and intra- and inter-day precisions were within 6% CV and 7% CV, respectively. Sample stability was demonstrated under various storage conditions, and the use of an internal standard conferred exceptional ruggedness. This method has been successfully applied for the determination of MPG and MPA in plasma, cornea, lens and retina following intraperitoneal administration of the drug in Wistar rats.
29930301 The role of neutrophil extracellular traps in rheumatic diseases. 2018 Aug Rheumatic diseases are a collection of disorders defined by the presence of inflammation and destruction of joints and internal organs. A common feature of these diseases is the presence of autoantibodies targeting molecules commonly expressed in neutrophils. These preformed mediators are released by neutrophils but not by other immune cells such as macrophages. Neutrophils, major players in the host innate immune response, initiate a cell death mechanism termed neutrophil extracellular trap (NET) formation as a way to ensnare pathogens. NETs are also a source of released self-molecules found in rheumatic diseases. Subsequently, research on the role of NETs in the onset, progression and resolution of inflammation in rheumatic diseases has intensified. This Review has two aims. First, it aims to highlight the mechanisms required for the generation of NETs, the research landscape of which is rapidly changing. Second, it aims to discuss the role of neutrophils and NETs in systemic lupus erythematosus, vasculitis (specifically anti-neutrophil cytoplasmic autoantibody-associated vasculitis), rheumatoid arthritis and gout. Our goal is to clarify the field of NET research in rheumatic diseases in the hope of improving the therapeutic approaches utilized for these diseases.
29701842 The Emerging Immunogenetic Architecture of Schizophrenia. 2018 Aug 20 Schizophrenia is a severe psychiatric disorder of complex etiology. Immune processes have long been proposed to contribute to the development of schizophrenia, and accumulating evidence supports immune involvement in at least a subset of cases. In recent years, large-scale genetic studies have provided new insights into the role of the immune system in this disease. Here, we provide an overview of the immunogenetic architecture of schizophrenia based on findings from genome-wide association studies (GWAS). First, we review individual immune loci identified in secondary analyses of GWAS, which implicate over 30 genes expressed in both immune and brain cells. The function of the proteins encoded by these immune candidates highlight the role of the complement system, along with regulation of apoptosis in both immune and neuronal cells. Next, we review hypothesis-free pathway analyses which have so far been inconclusive with respect to identifying immune pathways involved in schizophrenia. Finally, we explore the genetic overlap between schizophrenia and immune-mediated diseases. Although there have been some inconsistencies across studies, genome-wide pleiotropy has been reported between schizophrenia and Crohn's disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and ulcerative colitis. Overall, there are multiple lines of evidence supporting the role of immune genes in schizophrenia. Current evidence suggests that specific immune pathways are involved-likely those with dual functions in the central nervous system. Future studies focused on further elucidating the relevant pathways hold the potential to identify novel biomarkers and therapeutic targets for schizophrenia.
29183642 Tick-borne diseases and autoimmunity: A comprehensive review. 2018 Mar Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by ticks, which portray wide heterogeneity and global distribution. TBDs may present acute clinical pictures that resemble those of autoimmune diseases (i.e., musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal failure, etc.), and in some cases infection is considered a triggering factor for autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease, vasculitides). The clinician should consider TBDs among the differential diagnoses when approaching autoimmune-like signs in areas of tick infestation. Epidemiological setting (e.g., endemic areas, seasons) and an accurate diagnostic approach (i.e., clinical history, physical examination and laboratory tests) are necessary to confirm TBDs. Further, control and prevention of TBDs is warranted. Research in the fields of ticks microbiome and vaccination (i.e., wildlife and humans) are ahead to control vector transmission and bacterial infection. This review offers a comprehensive update on TBDs and their relationship with autoimmunity.
28914372 The role of gut microbiota in the pathogenesis of rheumatic diseases. 2018 Jan Rheumatic diseases refer to many diseases with a loss of immune self-tolerance, leading to a chronic inflammation, degeneration, or metabolic derangement in multiple organs or tissues. The cause of rheumatic diseases remains to be elucidated, though both environmental and genetic factors are required for the development of rheumatic diseases. Over the past decades, emerging studies suggested that alteration of intestinal microbiota, known as gut dysbiosis, contributed to the occurrence or development of a range of rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, and Sjogren's syndrome, through profoundly affecting the balance between pro- and anti-inflammatory immune responses. In this article, we discussed the role of gut microbiota in the pathogenesis of rheumatic diseases based on a large number of experimental and clinical materials, thereby providing a new insight for microbiota-targeted therapies to prevent or cure rheumatic diseases.
28757452 Will we ever have better glucocorticoids? 2018 Jan Glucocorticoids are cost-effective drugs with potent anti-inflammatory and immunosuppressive effects. They are used successfully to treat many disorders, including rheumatoid arthritis, polymyalgia rheumatic and other rheumatic diseases. However, these drugs also have the potential to cause adverse effects, particularly if high doses are used for prolonged periods. Therefore, continuous efforts are being made to implement recommendations for optimal dosing of glucocorticoids, monitoring for potential adverse events, adverse event prevention and management. Apart from this, novel and interesting work is underway to develop innovative glucocorticoids or glucocorticoid receptor ligands in order to improve the therapeutic balance. This article briefly mentions a recent publication discussing the question under which conditions long-term treatment with glucocorticoids has an acceptably low level of harm, and focuses then on two current approaches to minimize glucocorticoid adverse effects while keeping or even enhancing their anti-inflammatory efficacy, liposomal glucocorticoids and dissociated agonists of the glucocorticoid receptor.
29343461 Effects of Psychiatric Comorbidity in Immune-Mediated Inflammatory Disease: Protocol for a 2018 Jan 17 BACKGROUND: Immune-mediated inflammatory diseases (IMID), such as inflammatory bowel disease (IBD), multiple sclerosis (MS), and rheumatoid arthritis (RA), are highly prevalent in Canada and the United States and result in substantial personal and societal burden. The prevalence of psychiatric comorbidities, primarily depression and anxiety, in IMID exceeds those in the general population by two- to threefold, but remains underdiagnosed and undertreated. Furthermore, the effects of psychiatric comorbidity on IMID are not well understood. OBJECTIVE: The objectives of this study were (1) to compare health-related quality of life and work ability in persons with IMID and psychiatric comorbidity with those of persons with IMID without psychiatric comorbidity and with those of persons with depression and anxiety disorders alone, and (2) to validate existing case identification tools for depression and anxiety in persons with IMID to facilitate improved identification of depression and anxiety by clinicians. To achieve these objectives, we designed a prospective 3-year longitudinal study. In this paper, we aim to describe the study rationale and design and the characteristics of study participants. METHODS: Between November 2014 and July 2016, we recruited 982 individuals from multiple clinic and community sources; 18 were withdrawn due to protocol violations. RESULTS: The final study sample included 247 participants with IBD, 255 with MS, 154 with RA, and 308 with depression or anxiety. The majority were white, with the proportion ranging from 85.4% (IBD [210/246]; MS [217/254]) to 74.5% (114/153, RA; P=.01). There was a female predominance in all groups, which was highest in the RA cohort (84.4%, 130/154) and least marked in the IBD cohort (62.7%, 155/247). Participants with depression or anxiety were more likely to be single (36.0%, 111/308) than participants in any other group (11.8% [30/255]-22.7% [56/247], P<.001). CONCLUSIONS: This paper presents the rationale for this study, describes study procedures, and characterizes the cohort enrolled. Ultimately, the aim is improved care for individuals affected by IMID.
30116555 Prevalence and clinical correlates of rheumatoid factor and anticitrullinated protein anti 2018 OBJECTIVE: As rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPAs) are not routinely tested in idiopathic inflammatory myositis (IIM), little is known about their prevalence and clinical implications in this patient group. In antisynthetase syndrome (ASS), presence of ACPA is reportedly associated with more severe and erosive arthritis. We aim to retrospectively determine the prevalence of RF and ACPA in a cross-sectional cohort of 121 patients diagnosed with IIM and to assess clinical associations. METHODS: Serum samples from 121 patients diagnosed with polymyositis (n=30), dermatomyositis (n=41), ASS (n=37), inclusion body myositis (n=1), necrotising autoimmune myopathy (n=5) or overlap myositis (n=7) were analysed. RF was evaluated by nephelometry (Immage 800, Beckman-Coulter); anti-CCP antibodies were identified using fluoro enzyme immunoassays (Immuno-Cap 250, Thermo Fisher). Values above 40 IU/mL and 7 U/mL were considered positive for RF and ACPA, respectively. RESULTS: The prevalence of RF and ACPA was 9.09% and 4.96%, respectively. No significant differences were observed between RF/ACPA positive versus negative patients. There was a numerical trend for RF-positive IIM patients to be older and have lower forced expiratory volume in 1 s levels. CONCLUSIONS: RF and ACPA are prevalent in IIM, although we detected a lower prevalence than reported in previous studies. Presence of these antibodies in patients with IIM patients is not clinically relevant in our cohort.
30449652 Palliative and end-of-life care in rheumatology: High symptom prevalence and unmet needs. 2019 Aug OBJECTIVES: To determine the extent of end-of-life suffering and predictors of high symptom prevalence in the last one year of life in patients with systemic rheumatic diseases (SRDs) and the extent of supportive care received. METHODS: We identified adult patients with SRDs who died between 1 April 2006 and 1 April 2016. We collected data within 1 year before their death, on the following: (i) cumulative symptom prevalence, (ii) rates of Advance Care Planning (ACP), Do-Not-Resuscitate (DNR) orders and referral to a palliative physician. We analyzed the predictors of total symptom prevalence and palliative physician referral. RESULTS: Of the 161 patients studied, 34.2% had rheumatoid arthritis and 21.6% had systemic lupus erythematosus. Pain (81.4%), anorexia (80.1%) and dyspnea (77%) afflicted the majority of patients. On multivariate analysis, patients of the following profile had higher total symptom prevalence: (i) older age (β = 0.027, SE = 0.013, p = 0.044); (ii) more comorbidities measured by the Charlson Comorbidity Index (β = 0.192, SE = 0.159, p = 0.044); (iii) more admissions (β = 0.263, SE = 0.090, p = 0.004) and (iv) recurrent infections (β = 0.923, SE = 0.423, p = 0.031). Five patients (3.1%) received ACP and 25 (15.5%) were referred to a palliative physician. The median time between referral to palliative medicine and death was 8 days (IQR0-19). Of the 106 (67.5%) who had DNR orders, the median time between DNR and death was 3 days (IQR 0-10). CONCLUSIONS: Palliative and supportive care is relevant to patients with SRDs at the end-of-life. These patients experienced high physical suffering, particularly those who were elderly, with more comorbidities, hospital admissions and recurrent infections. Rheumatologists and physicians caring for patients with SRDs must be empowered to provide supportive care to these patients at the last phase of life, particularly by facilitating early ACP.
29955945 Association of gout with osteoporotic fractures. 2018 Sep PURPOSE: Previous studies have shown that serum uric acid levels and inflammation are associated with bone mineral density. Gout, a disease characterized by hyperuricemia and inflammation, contributes to the risk of osteoporotic fractures. However, this association is controversial. Therefore, this study investigated whether gout in older people (age > 55 years) is associated with osteoporotic fracture risk. METHODS: This population-based, cross-sectional study included 2674 participants (147 cases of gout and 388 fractures). Standardized and self-administered questionnaires were employed and physical examinations, blood tests, and bone mineral density examinations were performed; multivariate-adjusted logistic regression models were used to evaluate associations between gout and osteoporotic fracture risk. RESULTS: The data were adjusted for age; smoking status; alcohol status; physical activity; body mass index; waist circumference; hypertension; cardiovascular events; diabetes mellitus; rheumatoid arthritis; serum levels of total cholesterol (TC), triglycerides, and high- and low-density lipids; and T-scores. We found a significant association between gout and osteoporotic fracture risk in women (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.12-3.56; P = 0.019), but no such association in men (OR, 1.30; 95% CI, 0.58-2.88; P = 0.525). Further stratified analyses showed a significant association between gout and osteoporotic fracture risk in women without rheumatic arthritis and in those with high TC levels or with osteoporosis (all, P < 0.05). CONCLUSIONS: In older Chinese adults, gout is significantly associated with the risk of osteoporotic fractures in women, especially those without rheumatic arthritis and in those with high TC levels or with osteoporosis.
30477826 Yoga for systemic lupus erythematosus (SLE): Clinician experiences and qualitative perspec 2018 Dec Systemic lupus erythematosus (SLE) is an autoimmune disease associated with widespread inflammation and tissue damage. It is more common and severe among Blacks, Hispanics, and Asians; with higher incidence in women. While the goals of medical treatment are to prevent flares and reduce organ damage, up to 50% of patients perceive their health to be suboptimal with unaddressed needs including fatigue and pain. Recent SLE treatment guidelines focus on improving quality of life. Yoga has shown improvements in quality-of-life and fatigue in various diagnoses. While there is growing evidence that yoga therapy may help osteoarthritis and rheumatoid arthritis symptoms, there is only one reference in the literature related to SLE. METHODS/SETTING: An adjunct study was undertaken to evaluate adapting the Yoga as Self Care for Arthritis in Minority Communities study for a bilingual population living with SLE in the Washington, DC area. Informants included 7 patients enrolled onto the study, and 3 yoga instructors living with SLE. Qualitative methods included journals and semi-structured interviews. RESULTS: Enrolling patients clarified revisions for intake questionnaires, and symptoms that may impact class participation. Participants demonstrated increased balance, body awareness, and tolerated a faster-paced yoga class when compared to those in the parent study. Yoga instructors' recommendations included modifying yoga based on energy levels and frequent changes in physical ability. CONCLUSION: This paper shares perspectives from various informants and affirms the feasibility of progressing to a larger study. It summarizes our findings and recommendations towards creating a randomized controlled trial, as there are currently none in the literature.
29395681 Complement involvement in bone homeostasis and bone disorders. 2018 Jun An integral part of innate immunity is the complement system, a defence system, consisting of fluid-phase and cell surface-bound proteins. Its role to ensure adequate responses to danger factors and thus promoting host defence against pathogens has been well described already for decades. Recently, numerous further reaching functions of complement have been discovered, among these are tissue homeostasis and regeneration, also with respect to the skeletal system. The influence of complement activation on bone was recognised first in pathological conditions of inflamed bone tissue and surrounding areas, observed, for example, in rheumatoid arthritis and osteoarthritis. Greatly enhanced levels of complement proteins were detected in synovial fluids and sera of arthritic patients compared to healthy individuals. Additionally, complement-mediated signalling was shown to modulate periodontitis disease development and progression. Periodontitis is an infectious condition of the periodontium, which involves severe bone loss. Moreover, the complement system critically modulates bone regeneration and healing outcome after fracture. This is seen in uneventful fracture healing, but particularly under severe inflammatory conditions induced by an additional traumatic injury. Therefore, complement activation plays an important role in both sterile and non-sterile inflammatory conditions of the bone, which will be addressed here in respect of findings in bone fractures, arthritides, periodontitis and osteomyelitis. Importantly, complement proteins are thought to be critical not simply in the states of an activated immune system, but also for bone growth during physiological development and bone homeostasis, given for example their presence in long-bone growth-plate cartilage. Furthermore, bone-cell development from precursor cells and bone-cell metabolism and communication, for example, between bone-forming osteoblasts and bone-resorbing osteoclasts, are dependent on or even critically influenced by the presence of complement proteins and complement-mediated signalling. The present review summarises the current view on the role of the complement cascade on bone, both under homeostatic physiological conditions and under inflammatory and infectious conditions, which strongly affect the bone and skeletal health. Furthermore, this review addresses the potential and the feasibility of therapeutic interventions involving the complement cascade, derived from experimental and clinical data. Modulating the complement system could help in the future to reduce bone infections, ensure a balanced bone turnover and to generally improve skeletal health.
30199330 Characteristics and Outcome of Twenty-Nine Implant-Related Infections of the Hand and Fing 2018 Oct BACKGROUND: Implant-related infections in hand surgery are dreaded complications, potentially leading to loss of finger joint function or amputation. Knowledge about the clinical presentation and treatment concepts of these infections is limited. The aim of this study is to present a consecutive series of patients with implant-related infections of the finger joints and wrist. PATIENTS AND METHODS: We identified 25 patients with 29 implant-related infections. Infections were categorized as osteosynthesis-related infections (ORIs) or arthroplasty-related infections (ARIs). Further categorization included early and late post-operative (four weeks or less or more than four weeks after implantation) and exogenous and hematogenous infection. RESULTS: Compared with patients with ARIs (n = 11), those with ORIs (n = 14) were predominantly male (n = 11), were younger (mean 43 vs. 65 years, p = 0.0023), had few or no comorbidities, and had an exogenous source of infection. Patients with ARIs were predominantly female with rheumatoid arthritis (n = 8) and had a hematogenous pathogenesis. Infections occurred late in 22 (88%) patients. The most commonly isolated micro-organism was Staphylococcus aureus (n = 12; 48%). All ORIs were treated with implant removal and a median antimicrobial treatment duration of 39 days (interquartile range [IQR] 28-50 days). In the ARI group, the implant was removed in three patients and exchanged in three patients (one-stage exchange in one patient, two-stage exchange in two patients). In five individuals, debridement and implant retention was performed. The median antimicrobial treatment duration for ARIs was 42 days (IQR 30-75 days). The median follow-up time was 96 days (IQR 42-258 days) and infection was cured or presumably cured in 22 patients (88%). CONCLUSION: Our series shows distinct host and clinical patterns in ORIs and ARIs, supporting this categorization. The infection prognosis in ORIs is excellent with implant removal and antimicrobial treatment. Treatment concepts in ARIs are often derived from algorithms for periprosthetic joint infections of larger joints and need to be further elucidated.
30358903 Glucocorticoid activation by 11β-hydroxysteroid dehydrogenase enzymes in relation to infl 2019 Jan OBJECTIVE: Patients with chronic kidney disease (CKD) have dysregulated cortisol metabolism secondary to changes in 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes. The determinants of this and its clinical implications are poorly defined. METHODS: We performed a cross-sectional study to characterize shifts in cortisol metabolism in relation to renal function, inflammation and glycaemic control. Systemic activation of cortisol by 11β-HSD was measured as the metabolite ratio (tetrahydrocortisol [THF]+5α-tetrahydrocortisol [5αTHF])/tetrahydrocortisone (THE) in urine. RESULTS: The cohort included 342 participants with a median age of 63 years, median estimated glomerular filtration rate (eGFR) of 28 mL/min/1.73 m(2) and median urine albumin-creatinine ratio of 35.5 mg/mmol. (THF+5αTHF)/THE correlated negatively with eGFR (Spearman's ρ = -0.116, P = 0.032) and positively with C-reactive protein (ρ = 0.208, P < 0.001). In multivariable analysis, C-reactive protein remained a significant independent predictor of (THF+5αTHF)/THE, but eGFR did not. Elevated (THF+5αTHF)/THE was associated with HbA1c (ρ = 0.144, P = 0.008) and diabetes mellitus (odds ratio for high vs low tertile of (THF+5αTHF)/THE 2.57, 95% confidence interval 1.47-4.47). Associations with diabetes mellitus and with HbA1c among the diabetic subgroup were independent of eGFR, C-reactive protein, age, sex and ethnicity. CONCLUSIONS: In summary, glucocorticoid activation by 11β-HSD in our cohort comprising a spectrum of renal function was associated with inflammation and impaired glucose control.
30261673 Immune Response Targeting Sjögren's Syndrome Antigen Ro52 Suppresses Tear Production in F 2018 Sep 27 Autoantibodies reactive against Ro52 are present in 70% of Sjögren's syndrome patients and are associated with higher disease severity. However, their role in causing aqueous deficient dry eye, a major cause for morbidity in Sjögren's syndrome, is unclear. To investigate whether immune responses targeting Ro52 contribute towards the dry eye, male and female NZM2758 mice were immunized with recombinant Ro52. Tear production was measured by the phenol red thread test. Sera were analyzed for anti-Ro52 levels by immunoprecipitation. Lacrimal glands were evaluated for inflammatory foci and IgG deposits. Our results showed that, although all mice generated anti-Ro52 antibodies, only females developed a significant drop in tear production. None of the mice developed severe lacrimal gland inflammation, and female mice with anti-Ro52 showed higher levels of IgG deposits within their glands. Passive transfer of anti-Ro52 sera caused reduced tear production in female mice, but not in males. This study demonstrates for the first time that immune responses initiated by Ro52 induce aqueous dry eye, and this may be driven by anti-Ro52 antibodies. Furthermore, the sexual dimorphism in glandular dysfunction suggests that the lacrimal glands in females are more susceptible to autoantibody-mediated injury.
28941024 Association of High Mobility Group Box Chromosomal Protein 1 and Receptor for Advanced Gly 2018 Jun OBJECTIVE: To assess serum levels of high mobility group box chromosomal protein 1 (HMGB-1) and the soluble receptor for advanced glycation end products (sRAGE) in patients with Sjögren's syndrome (SS) and explore correlations with disease activity. METHODS: Thirty-nine patients with SS and 21 healthy controls were included in this cross-sectional study. Clinical and laboratory values were obtained from all patients. Disease activity was assessed using the European League Against Rheumatism SS Disease Activity Index (ESSDAI). Serum samples were collected and HMGB-1 and sRAGE levels were measured using enzyme-linked immunosorbent assay (ELISA), and HMGB-1 concentrations were semiquantified by Western blotting. RESULTS: In ELISA, HMGB-1 serum levels did not differ between healthy controls and patients with SS (P = 0.783). When measured by semiquantitative Western blotting, HMGB-1 levels were increased in patients with SS compared to healthy controls (P = 0.012). HMGB-1 serum levels detected by Western blotting were higher in patients with extraglandular manifestations (P = 0.003) and were correlated with ESSDAI disease activity (r = 0.544, P < 0.0001). Furthermore, sRAGE was elevated in the sera of patients with SS (P = 0.003) compared to healthy controls and was also correlated with the ESSDAI (r = 0.545, P = 0.002). CONCLUSION: Serum levels of total HMGB-1 and sRAGE were elevated in patients with SS compared to healthy controls and correlated with disease activity as measured by the ESSDAI. Patients with extraglandular involvement had high serum levels of HMGB-1.
29582130 Conventional radiography in juvenile idiopathic arthritis: Joint recommendations from the 2018 Sep BACKGROUND: Juvenile idiopathic arthritis (JIA) can cause structural damage. However, data on conventional radiography (CR) in JIA are scant. OBJECTIVE: To provide pragmatic guidelines on CR in each non-systemic JIA subtype. METHODS: A multidisciplinary task force of 16 French experts (rheumatologists, paediatricians, radiologists and one patient representative) formulated research questions on CR assessments in each non-systemic JIA subtype. A systematic literature review was conducted to identify studies providing detailed information on structural joint damage. Recommendations, based on the evidence found, were evaluated using two Delphi rounds and a review by an independent committee. RESULTS: 74 original articles were included. The task force developed four principles and 31 recommendations with grades ranging from B to D. The experts felt strongly that patients should be selected for CR based on the risk of structural damage, with routine CR of the hands and feet in rheumatoid factor-positive polyarticular JIA but not in oligoarticular non-extensive JIA. CONCLUSION: These first pragmatic recommendations on CR in JIA rely chiefly on expert opinion, given the dearth of scientific evidence. CR deserves to be viewed as a valuable tool in many situations in patients with JIA. KEY POINTS: • CR is a valuable imaging technique in selected indications. • CR is routinely recommended for peripheral joints, when damage risk is high. • CR is recommended according to the damage risk, depending on JIA subtype. • CR is not the first-line technique for imaging of the axial skeleton.
30219766 Presence of Autoantibodies in Erosive Hand Osteoarthritis and Association with Clinical Pr 2019 Jan OBJECTIVE: To investigate whether 3 rheumatoid arthritis-associated antibodies [rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) or anticarbamylated protein (anti-CarP) antibodies] are present in hand osteoarthritis (HOA) and associate with erosive OA (EOA). METHODS: Anti-CarP IgG was measured by ELISA in baseline sera of patients with HOA from 3 cohorts: HOSTAS (n = 510, 27.2% EOA), ECHO (n = 47), and EHOA (n = 23), and in sera of healthy controls (HC; n = 196, mean age 44.1 yrs, 51.0% women). Moreover, ACPA-IgG and RF-IgM were additionally determined in HOSTAS and HC. The prevalence of autoantibodies was compared between HOA and HC and between erosive and nonerosive HOA. In HOSTAS, hand radiographs were scored (Kellgren-Lawrence, Osteoarthritis Research Society International osteophyte and joint space narrowing) and C-reactive protein (CRP) levels, representing inflammation, were assessed. Groups were compared using nonparametric tests. RESULTS: The prevalence of anti-CarP was low and not significantly different between the total HOA group and HC (6.6% vs 3.6%, p = 0.12). In HOSTAS, the prevalence of all tested autoantibodies was low (anti-CarP 7.1%, ACPA 0.8%, RF 6.1%), and there were no significant differences observed between HOA patients and HC or between erosive and nonerosive HOA. Further, radiographic damage and CRP levels were similar in anti-CarP+ and anti-CarP-, and RF+ and RF- HOSTAS patients. CONCLUSION: The prevalence of autoantibodies is similar in HOA patients and HC, and these autoantibodies are not associated with erosive disease, structural damage, or inflammation in patients with HOA, indicating that another mechanism is driving erosive disease.
29934134 Protective role of commensal bacteria in Sjögren Syndrome. 2018 Sep CD25 knock-out (CD25KO) mice spontaneously develop Sjögren Syndrome (SS)-like inflammation. We investigated the role of commensal bacteria by comparing CD25KO mice housed in conventional or germ-free conditions. Germ-free CD25KO mice have greater corneal barrier dysfunction, lower goblet cell density, increased total lymphocytic infiltration score, increased expression of IFN-γ, IL-12 and higher a frequency of CD4(+)IFN-γ(+) cells than conventional mice. CD4(+) T cells isolated from female germ-free CD25KO mice adoptively transferred to naive immunodeficient RAG1KO recipients caused more severe Sjögren-like disease than CD4(+) T cells transferred from conventional CD25KO mice. Fecal transplant in germ-free CD25KO mice reversed the spontaneous dry eye phenotype and decreased the generation of pathogenic CD4(+)IFN-γ(+) cells. Our studies indicate that lack of commensal bacteria accelerates the onset and severity of dacryoadenitis and generates autoreactive CD4(+)T cells with greater pathogenicity in the CD25KO model, suggesting that the commensal bacteria or their metabolites products have immunoregulatory properties that protect exocrine glands in the CD25KO SS model.