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ID PMID Title PublicationDate abstract
31204589 A case of neutrophilic dermatosis with MEFV gene variant and abnormal activation of periph 2019 Mar A healthy 32-year-old man had a fever and elevated levels of white blood cells (WBC) and C-reactive protein (CRP). In addition, he presented with a skin rash on his forehead, around the neck, and from the anterior chest to the abdomen. His laboratory findings showed elevated levels of hepatic enzyme, CRP, and ferritin; therefore, he was suspected to have adult-onset Still's disease (AOSD) and referred to our department. We ruled out hematological malignancy and established diagnosis of AOSD according to Yamaguchi's criteria and treated with 20 mg/day prednisolone. His clinical condition did not improve, therefore, we increased the dosage of prednisolone to 40 mg/day; however, his rash gradually expanded with papules and plaques. A cervical skin biopsy revealed neutrophil dermatosis and analysis of the MEFV gene revealed a heterozygous variant in exon 2 (E148Q). We found an elevated percentage of CD86(+)CD14(+)CD16(-) classical monocytes in the peripheral blood using flow cytometry. We added oral potassium iodide as a treatment for neutrophil dermatosis. Despite this treatment, his eruption and fever did not subside, therefore, we changed potassium iodide to colchicine, this improved his clinical condition. This case suggests the importance of autoinflammation-related gene abnormalities and macrophage activation in the pathogenesis of neutrophil dermatosis.
31074727 The influence of immunosuppressants on the non-melanoma skin cancer among patients with sy 2019 Nov OBJECTIVES: To investigate the influence of corticosteroids and hydroxychloroquine on the association with non-melanoma skin cancer (NMSC) among patients with systemic lupus erythematosus (SLE) or primary Sjögren's syndrome (pSS). METHODS: This nationwide retrospective case-control study retrieved data from Taiwan National Health Insurance Research Database from 1995-2013. Cases with newly-diagnosed NMSC (n=19,603) and controls without NMSC were matched in a 1:1 ratio according to age, sex, and reference date. SLE, pSS, NMSC, and co-morbidities were determined by ICD-9-CM code. Cumulative drug exposures were defined by cumulative dosages or total defined daily dose (TDDD) of the Anatomical Therapeutic Chemical code of medicines. The analysis used conditional logistic regression and adjusted for age, sex, residential area, occupation, and co-morbidities. Case-control studies cannot infer the causality. RESULTS: Compared to patients without SLE or pSS, the patients with SLE had significantly higher associations with NMSC (cases/controls: n=23/10, adjusted odds ratio (AOR)=2.33, 95% confidence interval (CI) 1.08-5.01), particularly those using corticosteroids with a cumulative dosage >5g (cases/controls: n=17/5, AOR=2.96, 95%CI 1.06-8.23); and those using hydroxychloroquine with a cumulative dosage >100 TDDD (cases/controls: n=18/6, AOR=2.7, 95%CI 1.04-6.98). The patients with pSS had significantly higher associations with NMSC (cases/controls: n=28/11, AOR=2.56, 95%CI 1.25-5.23), particularly those using hydroxychloroquine with a cumulative dosage >100TDDD (cases/controls: n=20/4, AOR=5.41, 95%CI 1.82-16.11), and those using corticosteroids with a cumulative dosage >1g (cases/controls: n=13/3, AOR=4.92, 95%CI 1.37-17.61). CONCLUSIONS: The patients with SLE or pSS had significantly increased associations with NMSC, especially those receiving higher cumulative doses of corticosteroids and hydroxychloroquine.
31280278 Antifibrotics in interstitial lung disease related to connective tissue diseases - a parad 2019 Apr Interstitial lung disease (ILD) is one of the major causes of morbidity and mortality in patients with connective tissue disease (CTD) and the treatments available until nowadays are in most cases unable to halt disease progression. CTD-ILD pathogenesis includes an initial inflammatory phase, followed by a fibrotic phase, in which extracellular matrix proteins are produced and fibrotic scaring tissue within the lung develops. Steroids and immunosuppressants are the weapons we currently have to treat CTD-ILD. However, mortality rates remain high and identification of new therapeutic targets is crucial. Antifibrotic drugs, which include nintedanib and pirfenidone, have been approved for the treatment of idiopathic pulmonary fibrosis (IPF) and due to similar pathogenesis between IPF and CTD-ILD, their use seems attractive in patients with CTD-IL. We report 3 cases of patients with different CTDs, with predominantly fibrotic changes in high resolution computed tomography that progressed despite immunosuppression, and who have attained disease stability after introduction of antifibrotic drugs.
30906788 High-Risk Indicators of Renal Involvement in Primary Sjogren's Syndrome: A Clinical Study 2019 OBJECTIVE: A retrospective analysis of clinical characteristics and immunological manifestations of primary Sjogren's syndrome (pSS) patients with or without renal involvement was conducted in order to elucidate the potential risk factors of renal damage in pSS and evaluate the condition. METHODS: A total of 1002 patients, who fulfilled the 2002 classification criteria for pSS from the Second Affiliated Hospital of Shanxi Medical University, were enrolled in the cross-sectional study. Clinical, immunological, and histological characteristics were compared between pSS patients with and without renal involvement, and potential risk factors of renal involvements in pSS patients were examined by multivariate analysis. RESULTS: Among these pSS patients, there were 162 cases (16.17%) with and 840 cases (83.83%) without renal damage. Serious edema of both lower limbs, interstitial nephritis, and renal tubular acidosis were found in the pSS with renal damage group. Compared with simple pSS patients, the levels of creatinine, cystatin C, and alpha-1-microglobulin (α (1)-MG) in the pSS with renal damage group were significantly increased. The difference between the two groups was statistically significant (P < 0.05). The AUC of the combination of creatinine and α (1)-MG and creatinine, α (1)-MG, and creatinine was statistically larger than that of creatinine, and the biomarker of the biggest AUC is the combination of creatinine and α (1)-MG. CONCLUSION: The main clinical manifestations of pSS with renal damage were edema of the lower limbs, interstitial nephritis, and renal tubular acidosis. Creatinine and α (1)-MG are effective indicators for renal function in pSS, which may provide a better understanding for clinical decision-making.
30334118 Evaluation of subclinical atherosclerosis by ultrasound radiofrequency data technology in 2019 Mar Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease, and inflammation is highly associated with atherosclerosis and increased cardiovascular risk. Carotid intima-media thickness (CIMT) and arterial stiffness measurements are commonly used to detect subclinical atherosclerosis. The aim of this study was to non-invasively demonstrate the presence of subclinical atherosclerosis in patients with pSS through these measurements, using ultrasound (US) radiofrequency (RF) data technology. 30 pSS patients as the study group and 30 age-and sex-matched healthy volunteers as the control group were included in this study. The age of the participants in the entire sample ranged from 18 to 60 years, and no primary cardiovascular risk factors were present, such as diabetes mellitus, hypertension, hyperlipidemia, or obesity. The participants in the study and control groups were evaluated with doppler ultrasonography. Arterial stiffness and CIMT measurements were made from the bilateral common carotid arteries (CCA) using US RF data technology. No statistically significant difference was identified between the patients with pSS and the controls in terms of the right, left, and mean CCA IMT; the right side distensibility coefficient (DC) and compliance coefficient (CC); or the right- and left-side α and β stiffness indices values (p > 0.05). Compared to the control subjects, the pSS patients had higher right and left side pulsed wave velocity (PWV), the mean value of the right and the left sides α stiffness index, β stiffness index, and PWV (p < 0.05). The pSS patients' left DC, left CC, and the mean value of the right and left sides DC and CC were lower than controls (p < 0,05). It was found that patients with pSS show evidence of subclinical atherosclerosis. To determine this situation in patients with pSS, CIMT and PWV measurements may serve as a guide. Radiofrequency data technology represents a non-invasive approach to the accurate and quantitative measurement of CIMT elevation and decreases in vascular elasticity.
31672775 EULAR recommendations for the management of Sjögren's syndrome with topical and systemic 2020 Jan The therapeutic management of Sjögren syndrome (SjS) has not changed substantially in recent decades: treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. In view of this scenario, the European League Against Rheumatism (EULAR) promoted and supported an international collaborative study (EULAR SS Task Force) aimed at developing the first EULAR evidence and consensus-based recommendations for the management of patients with SjS with topical and systemic medications. The aim was to develop a rational therapeutic approach to SjS patients useful for healthcare professionals, physicians undergoing specialist training, medical students, the pharmaceutical industry and drug regulatory organisations following the 2014 EULAR standardised operating procedures. The Task Force (TF) included specialists in rheumatology, internal medicine, oral health, ophthalmology, gynaecology, dermatology and epidemiology, statisticians, general practitioners, nurses and patient representatives from 30 countries of the 5 continents. Evidence was collected from studies including primary SjS patients fulfilling the 2002/2016 criteria; when no evidence was available, evidence from studies including associated SjS or patients fulfilling previous sets of criteria was considered and extrapolated. The TF endorsed the presentation of general principles for the management of patients with SjS as three overarching, general consensus-based recommendations and 12 specific recommendations that form a logical sequence, starting with the management of the central triplet of symptoms (dryness, fatigue and pain) followed by the management of systemic disease. The recommendations address the use of topical oral (saliva substitutes) and ocular (artificial tear drops, topical non-steroidal anti-inflammatory drugs, topical corticosteroids, topical CyA, serum tear drops) therapies, oral muscarinic agonists (pilocarpine, cevimeline), hydroxychloroquine, oral glucocorticoids, synthetic immunosuppressive agents (cyclophosphamide, azathioprine, methotrexate, leflunomide and mycophenolate), and biological therapies (rituximab, abatacept and belimumab). For each recommendation, levels of evidence (mostly modest) and TF agreement (mostly very high) are provided. The 2019 EULAR recommendations are based on the evidence collected in the last 16 years in the management of primary 2002 SjS patients and on discussions between a large and broadly international TF. The recommendations synthesise current thinking on SjS treatment in a set of overarching principles and recommendations. We hope that the current recommendations will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations.
31486595 Evaluation of IL8 pathway on the ocular surface: new insights in patients with ocular muco 2020 Mar PURPOSE: To evaluate the expression of IL8/CXCL8 cytokine and its receptor CXCR1 in tear film and ocular surface of patients with ocular mucous membrane pemphigoid (oMMP). METHODS: Ten patients with oMMP in the quiescent phase, 20 patients with primary Sjogren syndrome (pSS) and 13 age- and sex-matched healthy controls (HCs) were included in this study. All patients undergone complete eye examination including lacrimal function tests and ocular surface staining assessed by ocular staining score. Ocular mucous membrane pemphigoid (oMMP) staging according to Mondino classification and dry eye severity grade according to Dry Eye Workshop 2007 classification were recorded. Tear samples and conjunctival epithelium were collected. IL-8 tear concentration was measured by enzyme-linked immunosorbent assay, and conjunctival IL8 was analysed by Western blot; conjunctival expression of CXCR1 was evaluated by immunohistochemistry. Il-8 and CXCR1 expression in oMMP patients were compared with HCand pSS patients and correlated with ocular clinical findings. RESULTS: Tear levels of IL-8 were significantly increased in patients with oMMP (260.1 ± 70 pg/ml) when compared to both HCs (98.5 ± 71.35 pg/ml; p = 0.001) and patients with pSS (96.3 ± 87.5 pg/ml; p = 0.001). Conjunctival expression of IL8 and CXCR1 was significantly increased in oMMP patients when compared to both healthy subjects and pSS patients. CONCLUSION: The significant increase of tear and conjunctival IL8 and CXCR1 levels in patients with oMMP when compared to healthy subjects and patients with Sjogren syndrome suggests that changes of IL8 pathway are specific of oMMP and may represent a potential biomarker of the disease and/or therapeutic target.
31110500 Subclinical Atherosclerosis in Primary Sjögren's Syndrome: Does Inflammation Matter? 2019 Sjögren's syndrome (SS) is a systemic autoimmune disease mainly characterized by inflammatory involvement of exocrine gland. Atherosclerosis is a complex process leading to plaque formation in arterial wall with subsequent cardiovascular (CV) events. Recently, numerous studies demonstrated that SS patients bear an increased CV risk. Since activation of immune system is a key element in atherosclerosis, it is interesting to analyze whether and how the autoimmune and inflammatory events characterizing SS pathogenesis directly or indirectly contribute to atherosclerosis risk in these patients. An increase in circulating endothelial microparticles and integrins, which may be a consequence of endothelial damage and impaired repair mechanisms, has been demonstrated in SS. Increased endothelial expression of adhesion molecules with subsequent infiltration of inflammatory cells into arterial wall is also a critical event in atherosclerosis. The early inflammatory events taking place in the atherosclerotic plaque cause an increase in alarmins, such as S100A8/A9, which seems to be associated with SS disease activity and, in turn, induce up-regulation of interleukin (IL)-1β and other pro-atherogenic cytokines. Interestingly, increased IL-1β levels were also detected in tertiary lymphoid structures developing in vessel adventitia adjacent to the atherosclerotic plaque, suggesting a direct role of IL-1β in this process. Similar to these structures, germinal center-like structures arising in SS exocrine glands are also tertiary lymphoid systems where T-helper (Th) cell subsets govern the adaptive immune response. Th1 cells are the most prevalent subtype and have been shown to be strongly involved in both SS pathogenesis and atherosclerosis. Th17 cells are attracting great interest and few studies showed its importance in SS development. Albeit in low amounts, a Th17 signature was also detected in atherosclerotic plaques and some animal models demonstrated a significant pro-atherogenic role and positive effects of IL-17A blockade. Despite the fact that T cells have a pivotal role in the inflammatory process that ultimately leads to atherosclerosis, B cells have also been detected in atherosclerotic plaques, although their exact role is still mostly unknown with studies showing contrasting results. In this scenario, the role of inflammation in atherosclerosis pathogenesis in patients with SS needs to be further explored.
31363829 Serum uric acid increases in patients with systemic autoimmune rheumatic diseases after 3 2019 Oct In patients with gout, the serum uric acid (SUA) is usually lower during acute gouty attacks than during intercritical periods. It has been suggested that systemic inflammatory response can cause this phenomenon. The objective is to determine whether therapy with TNF inhibitors (TNFis) affects SUA levels in patients with systemic autoimmune rheumatic diseases (SARDs) and whether SUA changes correlate with pro-inflammatory cytokines or with the oxidative stress marker allantoin. In this study, SUA, CRP, creatinine, MCP-1, IFN-α2, IFN-γ, Il-1β, IL-6, IL-8, IL-10, IL-12, IL-17a, IL-18, IL-23, IL-33, TNF-α, and allantoin levels were measured prior to and after 3 months of TNFis treatment in patients with SARDs. The values obtained in the biochemical assays were then tested for associations with the patients' demographic and disease-related data. A total of 128 patients (rheumatoid arthritis, n = 44; ankylosing spondylitis, n = 45; psoriatic arthritis, n = 23; and adults with juvenile idiopathic arthritis, n = 16) participated in this study. Among the entire patient population, SUA levels significantly increased 3 months after starting treatment with TNFis (279.5 [84.0] vs. 299.0 [102.0] μmol/l, p < 0.0001), while the levels of CRP, IL-6, IL-8, and MCP-1 significantly decreased. Male sex was the most powerful baseline predictor of ΔSUA in univariate and multivariate models. None of the measured laboratory-based parameters had statistically significant effects on the magnitude of ΔSUA. 3 months of anti-TNF therapy increased the levels of SUA in patients with SARDs, but neither the measured pro-inflammatory cytokines nor the oxidation to allantoin appeared responsible for this effect.
32226164 Clinical features and outcome of mixed connective tissue disease in developmental age - ob 2019 OBJECTIVES: Mixed connective tissue disease is a rare systemic connective tissue disease of developmental age and it includes the features of arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus and systemic sclerosis, with presence of anti-ribonucleoprotein antibodies (anti-RNP) in serum. Early diagnosis of the disease is difficult but essential in preventing development of systemic complications, which are often irreversible. International literature does not report many studies on large cohorts of children with this disease. The aim of this retrospective study was to define clinical characteristics and long-term results of treatment of the disease in 60 children with mixed connective tissue disease hospitalized in the period between 1978 and 2018. The diagnosis was established on the basis of Kasukawa's criteria. MATERIAL AND METHODS: It was a group of 60 children (46 girls and 16 boys) aged 10.5 on average (4-16.5). When assessing general symptoms at the onset of the disease according to Kasukawa's criteria, the highest number, over 80% of children, demonstrated symptoms suggesting SLE, about 40% suggesting DM and about 25% suggesting SSC. In the period of observation the number of children with clinical symptoms suggesting SSC increased. The most common clinical symptoms included Raynaud syndrome, arthritis and myositis and the most common irregularities in the test results included presence of anti-RNP antibodies and rheumatoid factor and hematological symptoms such as leukopenia/thrombocytopenia. Restrictive lung function impairment was demonstrated by 20% of children. Treatment most often included combined therapy (glucocorticosteroids + methotrexate/azathioprine). RESULTS: In 70% of the patients stable improvement was observed. Remission concerned 7% of the patients, frequent exacerbations were found in almost 20% of patients, and 2 children (3.5%) died. CONCLUSIONS: The long term observations of patients in developementeal age with mixed connective tissue disease revealed that the majority of them had domination of SLE symptoms, only in 7% achieved remission and 70% remained in stable improvement. Serious infections with septic state were the cause of death in two cases.
31391580 Locally renewing resident synovial macrophages provide a protective barrier for the joint. 2019 Aug Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis(1). However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy and single-cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of subsets of macrophages within healthy and inflamed joints, and study the roles of these macrophages during arthritis. We find that dynamic membrane-like structures, consisting of a distinct population of CX(3)CR1(+) tissue-resident macrophages, form an internal immunological barrier at the synovial lining and physically seclude the joint. These barrier-forming macrophages display features that are otherwise typical of epithelial cells, and maintain their numbers through a pool of locally proliferating CX(3)CR1(-) mononuclear cells that are embedded into the synovial tissue. Unlike recruited monocyte-derived macrophages, which actively contribute to joint inflammation, these epithelial-like CX(3)CR1(+) lining macrophages restrict the inflammatory reaction by providing a tight-junction-mediated shield for intra-articular structures. Our data reveal an unexpected functional diversification among synovial macrophages and have important implications for the general role of macrophages in health and disease.
30264875 Exposure measurement error when assessing current glucocorticoid use using UK primary care 2019 Feb PURPOSE: To quantify misclassification in glucocorticoid (GC) exposure defined using UK primary care prescription data. METHODS: A cross-sectional study including patients with rheumatoid arthritis prescribed oral GCs in the past 2 years. Glucocorticoid exposure based on electronic prescription records was compared with participant-reported GC use captured using a paper diary. Prescription data (containing information about prescriptions issued but no dispensing information) was provided by the Clinical Practice Research Datalink. The following variables were defined: current use and dose of oral GCs and if (and when) participants had received a GC injection. For oral GCs, self-reported use was taken to represent "true" exposure. A dataset representing a hypothetical population was generated to assess the impact of the misclassification found for current use. RESULTS: A total of 67 of 78 study participants (86%) were correctly classified as currently on/off oral GCs; 32/38 (84.2%) participants reporting current GC use and 35/40 (87.5%) participants not reporting current use were correctly classified. Estimated values of current dose were imprecise (correlation coefficient 0.46). Concordance between reported and prescribed GC injections was poor (kappa statistic 0.14). Misclassification bias was demonstrated in the hypothetical population: For "true" relative risks of 1.5, 4, and 9, the "observed" relative risks were 1.33, 2.48, and 3.58, respectively. CONCLUSIONS: Misclassification of current use of oral GCs was low but sufficient to lead to significant bias. Researchers should take care to assess the likely impact of exposure misclassification on their analyses.
31787331 Long-term outcomes of distal humeral epiphyseal separations treated via closed reduction a 2020 Feb BACKGROUND: The purpose of this study is to report the longterm radiological and clinical outcomes of the distal humeral epiphyseal separations (DHESs) treated by arthrogram-assisted closed pinning, retrospectively. METHODS: Among patients surgically treated from February 2000 to March 2010, 12 patients followed-up for at least 7 years were investigated. After careful inspection of initial simple radiographs, we performed intraoperative arthrogram for all children, confirmed DHES status, and concluded with closed reduction and pinning. At the final follow-up, the radiological and clinical outcomes were evaluated. RESULTS: The mean age at injury was 23.5 months, and four patients were male (42%). The mean age at final follow-up of 12 children/adolescents was 11.6 years. The mean follow-up period was 9.7 years (116.2 months). The dominant arm was injured in seven children. Two, seven, and three children were of the modified DeLee classifications A, B, and C, respectively. At the final follow-up, the mean humeral lengths of the injured and contralateral (normal) sides were 24.00 cm and 24.1 cm, thus not significantly different (P = 0.32). The final carrying angles were 10.75°, with significantly different with contralateral side (13.67°, P = 0.011). However, final shaft-condylar angles were not different (P = 0.207). There was no finding of avascular necrosis around trochlear area in all patients. The mean MEPS was satisfactory and the flexion/extension ranges were similar to those of the normal side (P = 0.317, 0.083). CONCLUSIONS: K-wire fixation via the arthrogram is useful when treating DHES, as it enhances anatomical reduction and minimizes later risk of cubitus varus. The clinical outcomes in school-age children and adolescents were satisfactory in most cases; however, longer follow-up of adolescents with cubitus varus is required. LEVEL OF EVIDENCE: Level IV, Therapeutic.
31575380 Proposal for a definition for response to treatment, inactive disease and damage for JIA a 2019 Oct 1 BACKGROUND: JIA-associated uveitis (JIAU) is a serious, sight-threatening disease with significant long-term complications and risk of blindness, even with improved contemporary treatments. The MIWGUC was set up in order to propose specific JIAU activity and response items and to validate their applicability for clinical outcome studies. METHODS: The group consists of 8 paediatric rheumatologists and 7 ophthalmologists. A consensus meeting took place on November 2015 in Barcelona (Spain) with the objective of validating the previously proposed measures. The validation process was based on the results of a prospective open, international, multi-centre, cohort study designed to validate the outcome measures proposed by the initial MIWGUC group meeting in 2012. The meeting used the same Delphi and nominal group technique as previously described in the first paper from the MIWGUC group (Arthritis Care Res 64:1365-72, 2012). Patients were included with a diagnosis of JIA, aged less than 18 years, and with active uveitis or an uveitis flare which required treatment with a disease-modifying anti-rheumatic drug. The proposed outcome measures for uveitis were collected by an ophthalmologist and for arthritis by a paediatric rheumatologist. Patient reported outcome measures were also measured. RESULTS: A total of 82 patients were enrolled into the validation cohort. Fifty four percent (n = 44) had persistent oligoarthritis followed by rheumatoid factor negative polyarthritis (n = 15, 18%). The mean uveitis disease duration was 3.3 years (SD 3.0). Bilateral eye involvement was reported in 65 (79.3%) patients. The main findings are that the most significant changes, from baseline to 6 months, are found in the AC activity measures of cells and flare. These measures correlate with the presence of pre-existing structural complications and this has implications for the reporting of trials using a single measure as a primary outcome. We also found that visual analogue scales of disease activity showed significant change when reported by the ophthalmologist, rheumatologist and families. The measures formed three relatively distinct groups. The first group of measures comprised uveitis activity, ocular damage and the ophthalmologists' VAS. The second comprised patient reported outcomes including disruption to school attendance. The third group consisted of the rheumatologists' VAS and the joint score. CONCLUSIONS: We propose distinctive and clinically significant measures of disease activity, severity and damage for JIAU. This effort is the initial step for developing a comprehensive outcome measures for JIAU, which incorporates the perspectives of rheumatologists, ophthalmologists, patients and families.
31473619 C reactive protein level as a marker for dyslipidaemia, diabetes and metabolic syndrome: r 2019 Aug 30 OBJECTIVE: Plasma C reactive protein (CRP) is a marker of inflammation, and increased plasma CRP is reported in many diseases, including cardiovascular disease, diabetes, metabolic syndrome, arthritis and malignancies. The aim of the study was to evaluate the association between plasma CRP levels and cardiovascular disease, metabolic syndrome, malignancies and other comorbidities. DESIGN: A retrospective, cross-sectional survey study. SETTING: Large population survey in Korea. METHODS: A total of 5887 (weighted n=40 251 868) participants aged 19 years or older from the 2016 Korea National Health and Nutrition Examination Survey were included for analysis. Weighted prevalence and OR of comorbidities were analysed according to the continuous variable of log plasma high-sensitivity CRP levels. RESULTS: The mean age was 46.7±0.37 years and the median plasma CRP was 0.58 mg/L (IQR 0.36-1.09). The mean plasma CRP levels were higher in participants with cardiovascular diseases and cardiovascular risk factors, osteoarthritis, rheumatoid arthritis, pulmonary tuberculosis, and several cancers, including gastric, colon, breast and cervix, than in the general population. In the multivariable analysis, plasma CRP concentration was associated with increased prevalence of hypertriglyceridaemia (OR 1.157, 95% CI 1.040 to 1.287, p=0.007), diabetes (OR 1.204, 95% CI 1.058 to 1.371, p=0.005) and metabolic syndrome (OR 1.228, 95% CI 1.112 to 1.357, p<0.001) after adjustment for socioeconomic and lifestyle characteristics. There was no significant association between plasma CRP level and cancers. CONCLUSION: Plasma CRP was associated with an increased risk of dyslipidaemia, diabetes and metabolic syndrome in the general population.
30732563 A case report of severe recurrent varicella in an ankylosing spondylitis patient treated w 2019 Feb 7 BACKGROUND: Tumor necrosis factor-α (TNF-α) antagonists, most of which are monoclonal antibodies, became a widespread treatment for autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, psoriasis, psoriatic arthritis, hidradenitis suppurativa and uveitis. Their use is based on the blockage of TNF-α, which plays an important role in granulomas formation, development of phagosomes, activation and differentiation of macrophages, immune response against viral pathogens. The multiple adverse effects of TNF-α inhibition have been identified, including a two-to four-fold increased risk of active tuberculosis and other granulomatous conditions and an increased occurrence of some other serious bacterial, fungal and certain viral infections. CASE PRESENTATION: A 34-year-old male patient with disseminated varicella and pneumonitis was admitted to our hospital. The diagnosis of varicella was established serologically by enzyme immunoassay (EIA) and by polymerase chain reaction confirmation of the virus in vesicular fluid. The patient has been receiving adalimumab and methotrexate for the last 3 years due to ankylosing spondylitis and was seropositive to varicella zoster virus prior to the introduction of TNF-α antagonists. Acyclovir was administered for 10 days with the resolution of clinical illness and radiological signs of pneumonitis. CONCLUSION: Due to the use of biological agents, particularly TNF-α inhibitors, as a well-established therapy for some autoimmune diseases, new potential adverse events can be expected in the future and we wanted to point out one of them. To our knowledge this is the first case of recurrent disseminated varicella in a patient taking TNF-α antagonists.
31796497 The 2019 American College of Rheumatology/European League Against Rheumatism classificatio 2020 Jan IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serological, radiological and pathological data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4-RD. An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Investigators used consensus exercises; existing literature; derivation and validation cohorts of 1879 subjects (1086 cases, 793 mimickers); and multicriterion decision analysis to identify, weight and test potential classification criteria. Two independent validation cohorts were included. A three-step classification process was developed. First, it must be demonstrated that a potential IgG4-RD case has involvement of at least one of 11 possible organs in a manner consistent with IgG4-RD. Second, exclusion criteria consisting of a total of 32 clinical, serological, radiological and pathological items must be applied; the presence of any of these criteria eliminates the patient from IgG4-RD classification. Third, eight weighted inclusion criteria domains, addressing clinical findings, serological results, radiological assessments and pathological interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% CI 97.2% to 99.8%) and a sensitivity of 85.5% (95% CI 81.9% to 88.5%). In the second, the specificity was 97.8% (95% CI 93.7% to 99.2%) and the sensitivity was 82.0% (95% CI 77.0% to 86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds. ACR/EULAR classification criteria for IgG4-RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiological and basic science investigations.
31231373 Downregulation of Transcription Factor T-Bet as a Protective Strategy in Monosodium Urate- 2019 Gout is sterile joint inflammation triggered by the damaging effects of monosodium urate (MSU) crystals accumulation. Previous studies suggest transcription factor T-bet plays an important role in inflammatory arthritis. Notably, mice lacking T-bet markedly reduced joint inflammation of rheumatoid arthritis models, however, the involvement of T-bet in gouty inflammation has yet to be clarified. Here, we took advantage of T-bet knockout (KO) mice to investigate the role of T-bet in the pathogenesis of MSU-induced gout inflammation. T-bet KO and wild type (WT) mice were used for models of acute inflammation induced with MSU crystals, including footpad, air pouch and peritonitis models. Inflammatory cytokines and phagocytosis were detected in bone-marrow-derived macrophages (BMDMs) from T-bet KO and WT mice treated with MSU crystals in vitro. In addition, T-bet expression in peripheral blood mononuclear cells (PBMCs) from gout patients was measured, as well as plasma inflammatory cytokines. We found that the levels of interleukin (IL)-17, IL-23, and interferon-γ were reduced, but tumor necrosis factor-α was not, in BMDMs from T-bet KO compared with WT mice after MSU challenge in vitro, as well as MSU phagocytosis. In comparison with WT mice in vivo, the swelling index of T-bet KO mice was significantly decreased in the footpad model. T-bet deficiency also dramatically relieved MSU-induced inflammatory cell infiltration in peritonitis and air pouch models in vivo, and as well as the IL-1β levels of air pouch lavage fluid (APLF). In addition, plasma IL-17 and IL-23 levels were elevated in acute gout, whereas protein levels of T-bet were downregulated in PBMCs from acute gout patients and intercritical gout treated with MSU crystals in vitro as well. Transcription factor T-bet deficiency protects against MSU-induced gouty inflammation, suggesting that downregulation of T-bet could be a protective strategy and contribute to spontaneous remission of inflammation in acute gout.
30572134 Disease activity assessment of rheumatic diseases during pregnancy: a comprehensive review 2019 Feb Pregnancy requires a special management in women with inflammatory rheumatic diseases (RDs), with the aim of controlling maternal disease activity and avoiding fetal complications. Despite the heterogeneous course of RDs during pregnancy, their impact on pregnancy largely relates to the extent of active inflammation at the time of conception. Therefore, accurate evaluation of disease activity is crucial for the best management of pregnant patients. Nevertheless, there are limitations in using conventional measures of disease activity in pregnancy, as some items included in these instruments can be biased by symptoms or by physiological changes related to pregnancy and the pregnancy itself may influence laboratory parameters used to assess disease activity. This article aims to summarize the current literature about the available instruments to measure disease activity during pregnancy in RDs. Systemic lupus erythematosus is the only disease with instruments that have been modified to account for several adaptations which might interfere with the attribution of signs or symptoms to disease activity during pregnancy. No modified-pregnancy indices exist for women affected by other RDs, but standard indices have been applied to pregnant patients. The current body of knowledge shows that the physiologic changes that occur during pregnancy need to be either adapted from existing instruments or developed to improve the management of pregnant women with RDs. Standardized instruments to assess disease activity during pregnancy would be helpful not only for clinical practice but also for research purposes.
30459279 Humanised effector-null FcγRIIA antibody inhibits immune complex-mediated proinflammatory 2019 Feb OBJECTIVE: Immune complexes (ICs) play a critical role in the pathology of autoimmune diseases. The aim of this study was to generate and characterise a first-in-class anti-FcγRIIA antibody (Ab) VIB9600 (previously known as MEDI9600) that blocks IgG immune complex-mediated cellular activation for clinical development. METHODS: VIB9600 was humanised and optimised from the IV.3 Ab. Binding affinity and specificity were determined by Biacore and ELISA. Confocal microscopy, Flow Cytometry-based assays and binding competition assays were used to assess the mode of action of the antibody. In vitro cell-based assays were used to demonstrate suppression of IC-mediated inflammatory responses. In vivo target suppression and efficacy was demonstrated in FcγRIIA-transgenic mice. Single-dose pharmacokinetic (PK)/pharmacodynamic study multiple dose Good Laboratory Practice (GLP) toxicity studies were conducted in non-human primates. RESULTS: We generated a humanised effector-deficient anti-FcγRIIA antibody (VIB9600) that potently blocks autoantibody and IC-mediated proinflammatory responses. VIB9600 suppresses FcγRIIA activation by blocking ligand engagement and by internalising FcγRIIA from the cell surface. VIB9600 inhibits IC-induced type I interferons from plasmacytoid dendritic cells (involved in SLE), antineutrophil cytoplasmic antibody (ANCA)-induced production of reactive oxygen species by neutrophils (involved in ANCA-associated vasculitis) and IC-induced tumour necrosis factor α and interleukin-6 production (involved in rheumatoid arthritis). In FcγRIIA transgenic mice, VIB9600 suppressed antiplatelet antibody-induced thrombocytopaenia, acute anti-GBM Ab-induced nephritis and anticollagen Ab-induced arthritis. VIB9600 also exhibited favourable PK and safety profiles in cynomolgus monkey studies. CONCLUSIONS: VIB9600 is a specific humanised antibody antagonist of FcγRIIA with null effector function that warrants further clinical development for the treatment of IC-mediated diseases.