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ID PMID Title PublicationDate abstract
32472559 Evaluating the preventive and curative effects of Toxocara canis larva in Freund's complet 2020 Nov Helminthic infection and the parallel host immune reactions are the results of a protracted dynamic co-interaction between the host and worms. An assessment of the effect of Toxocara canis infection on arthritis in rats stimulated by Freund's complete adjuvant (FCA) was the main purpose of the investigation. An arthritis model was established by the administration of 0.1 mL FCA in the palmar surface. Cytokine assessment, evaluating oedema and the use of a rheumatoid arthritis (RA) score provided evidence of the protective effects of T canis against adjuvant-induced arthritis (AIA). The cytokines TGF-β, IFN-ɣ, IL-10 and IL-17 were measured to assess the anti-inflammatory effect of T canis infection. Besides, arthritis swelling findings were evaluated in rat paws. The data showed that T canis infection significantly modulated the immune response by alleviating inflammatory cytokines and increasing TGF-β as an anti-inflammatory cytokine. Evaluations of arthritis swelling showed low severity and faster recuperation. These findings suggest that the products derived from T canis eggs might be a potential therapeutic candidate to treat autoimmune diseases like the arthritis.
32170838 Modified Disease Activity Score at 3 Months Is a Significant Predictor for Rapid Radiograp 2020 Mar OBJECTIVE: Progressive rheumatoid arthritis (RA) is responsible for joint damage causing disabilities, but there is no agreement on which disease measures best predict radiographic progression. We aimed to determine which disease activity measures, including the disease activity score, the modified disease activity score in 28 joints with C-reactive protein testing (M-DAS28-CRP), the Clinical Disease Activity Index, and the Health Assessment Questionnaire Disability Index, at baseline and 3 months best predicted rapid radiographic progression (RRP) in patients with early RA. METHODS: Data were used from PREMIER, a 2-year, multicenter, double-blind, active comparator controlled study with methotrexate (MTX)-naïve patients with RA and active disease for less than 3 years. Treatments included adalimumab plus oral MTX, adalimumab, or oral MTX. Only patients in the MTX arm were analyzed in this study. RRP was defined as a change in the modified total Sharp score of less than 3.5 at month 12. The logistic regression analysis assessed the impact of measures at baseline and 3 months on RRP at 12 months. Best cutoff points of the M-DAS28-CRP were also estimated by using area under the receiver operating characteristic curve. RESULTS: A total of 149 patients were included (female patients: n = 113 [75.8%]; positive rheumatoid factor: n = 127 [85.2%]; mean [SD] age: 52.9 [13.3] years; mean [SD] disease duration: 0.8 [0.9] year; mean [SD] M-DAS28-CRP: 6.3 [0.9]). After adjusting for potential confounders, only the M-DAS28-CRP at baseline (adjusted odds ratio [AOR] = 3.29; 95% confidence interval [CI]: 1.70-6.36) and 3 months (AOR = 2.56; 95% CI: 1.43-4.56) strongly predicted RRP at 12 months. M-DAS28-CRP of 4.5 and 2.6 at baseline and 3 months, respectively, maximized positive and negative predictive values for prediction of RRP. CONCLUSION: The M-DAS28-CRP was a stronger predictor at baseline and 3 months for RRP compared with other disease activity measures. Removing tender joint count and patient global assessment from the DAS28-CRP improves prediction of RRP.
32512639 Work disability in rheumatic diseases: Baseline results from an inception cohort. 2020 Aug AIM: We aimed to characterize work disability in patients with newly diagnosed rheumatic diseases and compare work characteristics between patients with rheumatic diseases and controls without rheumatic diseases at diagnosis. METHODS: Patients with inflammatory arthritis (IA) and osteoarthritis (OA), surrogates for autoimmune and non-autoimmune rheumatic diseases, respectively, and controls of working age were surveyed at diagnosis. Patients with rheumatic diseases who were employed before symptom onset were characterized as having work disability if they reported reduced work ability and productivity while remaining in the same job as before symptom onset, changed to a less demanding job or stopped working/retired. Work characteristics at diagnosis were compared between rheumatic diseases patients and controls. RESULTS: The unemployment rate before symptom onset was lower in patients with IA (20%) compared to patients with OA (32%). Among patients with IA and OA who were employed before symptom onset, 59% and 43% reported work disability, respectively (P = .04). The unemployment rate at diagnosis was comparable in patients with IA (26%) and higher in patients with OA (38%) compared to controls (29%). Employed patients with IA and OA, when compared with controls, reported poorer work ability (score: 37 vs 39 vs 41, P < .01; proportion with poor/moderate work ability: 48% vs 33% vs 21%, P < .01) and greater work productivity loss (score: 32 vs 29 vs 17, P < .01) at diagnosis. CONCLUSION: Rheumatic diseases impose significant work disability at diagnosis, highlighting the need for identification and interventions targeting work disability early in the course of disease.
32851364 Factors Predicting Early Failure of Etanercept in Rheumatoid Arthritis: An Analysis From t 2020 Jun OBJECTIVES: This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis; GISEA) registry. PATIENTS AND METHODS: This registry-based cohort study included 477 RA patients (95 males, 382 females; median age 53 years; range 18 to 83 years) who began ETA as first bDMARD. Patient demographics, disease features and drugs were re-evaluated after 12 months. Baseline predictors of ETA discontinuation were estimated by univariate and multivariate analyses using Cox regression model. RESULTS: Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 55.8%, adverse events in 28.6%, and other reasons in 6.5%). Concurrent conventional synthetic DMARDs (csDMARDs) were reported in 54.3% of patients, mainly methotrexate (MTX), while 52.4% of subjects took low doses of glucocorticoids. Patients stopping ETA more frequently showed one or more comorbidities, mainly cardiovascular diseases (28.6% vs. 15.7% in patients stopping and continuing ETA, respectively, p=0.009). The presence of comorbidities and a combination therapy with csDMARDs other than MTX were independent factors associated with early discontinuation of ETA at multivariate Cox analysis. CONCLUSION: Although ETA demonstrated a high persistence in biologic-naïve RA patients, about 15% of patients discontinued the treatment within 12 months. The presence of comorbidities and a combination therapy with csDMARDs other than MTX were the main factors for an early withdrawal of the drug.
32218599 Exacerbation of symptomatic arthritis by cigarette smoke in experimental arthritis. 2020 INTRODUCTION: Epidemiologically, cigarette smoking is a well-known risk factor for the pathogenesis of rheumatoid arthritis (RA). However, there has been few plausible explanations why cigarette smoking aggravated RA. We investigated the causal effect of smoking in experimental model of arthritis development. METHODS: During induction of experimental arthritis with collagen challenge, mice were exposed to a smoking environment with 3R4F cigarettes. Generated smoke was delivered to mice through a nose-only exposure chamber (ISO standard 3308). Human cartilage pellet was challenged by cigarette smoke extract to identify citrullinating potential in vitro. RESULTS: Cigarette smoke exacerbated arthritis in a collagen-induced arthritis (CIA) model. Exposure to smoke accelerated the onset of arthritis by 2 weeks compared to the conventional model without smoke. Citrullination of lung tissue as well as tarsal joints were revealed in smoke-aggravated CIA mice. Interestingly, tracheal cartilage was a core organ regarding intensity and area size of citrullination. The trachea might be an interesting organ in viewpoint of sharing cartilage with joint and direct smoke exposure. Anti-CCP antibodies were barely detected in the serum of CIA mice, they were significantly elevated in cigarette smoke group. Citrullinated antigens were increased in the serum of smoke-exposed mice. Lastly, a cigarette smoke extract enhanced human cartilage citrullination in vitro. CONCLUSIONS: Missing link of arthritic mechanism between smoke and RA could be partially explained by tracheal citrullination. To control tracheal cartilage citrullination may be beneficial for preventing arthritis development or aggravation if cigarette smoke is becoming a risk factor to pre-arthritic individual.
32370139 Effect of Dysmetabolisms and Comorbidities on the Efficacy and Safety of Biological Therap 2020 May 2 In the present study we evaluated how systemic arterial hypertension (SAH), dyslipidemia and diabetes mellitus influence the efficacy, safety and retention rate of biological disease-modifying anti-rheumatic drug (bDMARD) treatment in rheumatic musculoskeletal disorders (RMDs). The charts of RMD patients treated with the first-line bDMARD were reviewed, collecting data on safety, efficacy and comorbidities at prescription (baseline, BL), after 6 months (6M) and at last observation on bDMARD (last observation time, LoT). In 383 RMD patients, a higher rate of adverse events at 6M (p = 0.0402) and at LoT (p = 0.0462) was present in dyslipidemic patients. Patients who developed dyslipidemia or SAH during bDMARD treatment had similar results (dyslipidemia p = 0.0007; SAH p = 0.0319) with a longer bDMARD retention as well (dyslipidemia p < 0.0001; SAH p < 0.0001). SAH patients on angiotensin converting enzyme inhibitors (ACEis) or angiotensin-II receptor blockers (ARBs) continued bDMARDs for longer than non-exposed patients (p = 0.001), with higher frequency of drug interruption for long-standing remission rather than inefficacy or adverse reactions (p = 0.0258). Similarly, dyslipidemic patients on statins had a better bDMARD retention than not-exposed patients (p = 0.0420). In conclusion, SAH and dyslipidemia may be associated with higher frequency of adverse events but a better drug retention of first-line bDMARD in RMDs, suggesting an additional effect of ACEis/ARBs or statins on the inflammatory process and supporting their use in RMD bDMARD patients with SAH/dyslipidemia.
32180363 Increased CD200 levels in peripheral blood mononuclear cells of patients with primary Sjö 2020 May OBJECTIVES: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with an unknown etiology. CD200 is associated with many autoimmune diseases, but little is known about its role in pSS. This study aims to correlate the expression of CD200 with pSS and evaluate its significance. METHODS: Plasma CD200, CD200R, and interleukin (IL)-17 levels were measured and analyzed by enzyme-linked immunosorbent assay. Messenger RNA levels of CD200 and CD200R in peripheral blood mononuclear cells (PBMCs) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR). Following pretreatment of CD200-Fc, the protein levels of IL-17A were measured in PBMCs from patients and healthy controls. RESULTS: Results showed that, compared to CD200 in healthy controls, the relative levels in PBMCs from pSS were greater than 2-fold. In addition, CD200 levels in plasma positively correlated with IL-17 levels, as well as between plasma CD200 and pSS activity indexes (including immunoglobulin G and European League Against Rheumatism SS Disease Activity Index). While CD200R levels were significantly decreased in pSS patients, no correlation could be found. Furthermore, the protein level of IL-17 decreased after pretreatment of CD200-Fc in PBMCs from pSS patients. CONCLUSION: Our results suggested that the CD200/CD200R pathway is involved in pSS pathogenesis. It is hypothesized that regulation of IL-17 expression affects Th17 differentiation. This newly discovered pathway could give rise to a novel targeted therapy for pSS.
31733111 Decreased circulating CXCR3 + CCR9+T helper cells are associated with elevated levels of 2020 Mar CCR9 + T helper (Th) cells can induce Sjögren-like symptoms in mice and both CCR9 + Th cells and their ligand CCL25 are increased in the salivary glands of primary Sjögren's syndrome (pSS) patients. Increased circulating CCR9 + Th cells are present in pSS patients. CCR9 + Th cells are hyperresponsive to IL-7, secrete high levels of IFN-γ, IL-21, IL-17 and IL-4 and potently stimulate B cells in both patients and healthy individuals. Our aim was to study co-expression of chemokine receptors on CCR9 + Th cells and whether in pSS this might differentially affect CCR9 + Th cell frequencies. Frequencies of circulating CCR9 + and CCR9- Th cells co-expressing CXCR3, CCR4, CCR6 and CCR10 were studied in pSS patients and healthy controls. CCL25, CXCL10, CCL17, CCL20 and CCL27 mRNA and protein expression of salivary gland tissue of pSS and non-Sjögren's sicca (non-SS) patients was assessed. Chemotaxis assays were performed to study migration induced by CXCL10 and CCL25. Higher expression of CXCR3, CCR4 and CCR6 but not CCR10 was observed on CCR9 + Th cells as compared to cells lacking CCR9. Decreased frequencies of circulating memory CCR9 + CXCR3+ Th cells were found in pSS patients, which was most pronounced in the effector memory subset. Increased salivary gland CCL25 and CXCL10 expression significantly correlated and both ligands functioned synergistically based on in vitro induced chemotaxis. Decreased memory CXCR3 + CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation in the salivary glands facilitating their preferential migration and positioning in the lymphocytic infiltrates.
32686529 Expression of NGAL-specific cells and mRNA levels correlate with inflammation in the saliv 2020 Sep Salivary gland involvement is a characteristic feature of primary Sjögren's syndrome (pSS), where tissue destruction is mediated by infiltrating immune cells, and may be accompanied by the presence of adipose tissue. Optimally diagnosing this multifactorial disease requires the incorporation of additional routines. Screening for disease-specific biomarkers in biological fluid could be a promising approach to increase diagnostic accuracy. We have previously investigated disease biomarkers in saliva and tear fluid of pSS patients, identifying Neutrophil gelatinase-associated lipocalin (NGAL) as the most upregulated protein in pSS. In the current study, we aimed to explore for the first time NGAL expression at the site of inflammation in the pSS disease target organ. Immunohistochemical staining was conducted on minor salivary gland biopsies from 11 pSS patients and 11 non-SS sicca subjects, targeting NGAL-specific cells. Additional NGAL/PNAd double staining was performed to study NGAL expression in high endothelial venules, known as specialised vascular structures. Moreover, NGAL mRNA expression was measured utilising quantitative real-time polymerase chain reaction (qRT-PCR) on minor salivary gland biopsies from 15 pSS patients and 7 non-SS sicca individuals that served as tissue controls. Our results demonstrated NGAL expression in acinar and ductal epithelium within the salivary gland of pSS patients, where significantly greater levels of acinar NGAL were observed in pSS patients (p < .0018) when compared to non-SS subjects. Also, acinar expression positively correlated with focus score values (r (2) = 0.54, p < .02), while ductal epithelial expression showed a negative such correlation (r (2) = 0.74, p < .003). Some PNAD(+) endothelial venules also expressed NGAL. An increase in NGAL staining with increased fatty replacement was also observed in pSS patients. Concurringly, a 27% increase in NGAL mRNA levels were also detected in the minor salivary glands of pSS patients when compared to non-SS tissue control subjects. In conclusion, there is a positive association between increase in NGAL expression and inflammation in the pSS disease target organ, which also coincides with its previously demonstrated upregulation in the saliva of pSS patients. Additional functional analyses are needed to better understand the immunological implications of this potential biomarker.
32201227 Gene expression profiling of epithelium-associated FcRL4(+) B cells in primary Sjögren's 2020 May In primary Sjögren's syndrome (pSS), FcRL4(+) B cells are present in inflamed salivary gland tissue, within or in close proximity to ductal epithelium. FcRL4 is also expressed by nearly all pSS-related mucosa-associated lymphoid tissue (MALT) B cell lymphomas, linking FcRL4 expression to lymphomagenesis. Whether glandular FcRL4(+) B cells are pathogenic, how these cells originate, and how they functionally differ from FcRL4(-) B cells in pSS is unclear. This study aimed to investigate the phenotype and function of FcRL4(+) B cells in the periphery and parotid gland tissue of patients with pSS. First, circulating FcRL4(+) B cells from 44 pSS and 54 non-SS-sicca patients were analyzed by flow cytometry. Additionally, RNA sequencing of FcRL4(+) B cells sorted from parotid gland cell suspensions of 6 pSS patients was performed. B cells were sorted from cell suspensions as mini bulk (5 cells/well) based on the following definitions: CD19(+)CD27(-)FcRL4(-) ('naive'), CD19(+)CD27(+)FcRL4(-) ('memory'), and CD19(+)FcRL4(+) B cells. We found that, although FcRL4(+) B cells were not enriched in blood in pSS compared with non-SS sicca patients, these cells generally exhibited a pro-inflammatory phenotype. Genes coding for CD11c (ITGAX), T-bet (TBX21), TACI (TNFRSF13B), Src tyrosine kinases and NF-κB pathway-related genes were, among others, significantly upregulated in glandular FcRL4(+) B cells versus FcRL4(-) B cells. Pathway analysis showed upregulation of B cell activation, cell cycle and metabolic pathways. Thus, FcRL4(+) B cells in pSS exhibit many characteristics of chronically activated, pro-inflammatory B cells and their gene expression profile suggests increased risk of lymphomagenesis. We postulate that these cells contribute significantly to the epithelial damage seen in the glandular tissue and that FcRL4(+) B cells are an important treatment target in pSS.
32047959 Serum CXCL13 levels are associated with lymphoma risk and lymphoma occurrence in primary S 2020 Apr Primary Sjögren's syndrome (pSS) is an autoimmune disease characterised by an increased risk for non-Hodgkin lymphoma (NHL) development. Ectopic germinal centre (GC) in the salivary gland is associated with increased NHL risk in pSS, and the chemokine CXCL13 is implicated in B-cell migration and GC formation. Serum CXCL13 concentrations were quantified by ELISA in 48 healthy individuals, 273 pSS patients without NHL (pSS-nonL), and 38 pSS patients with NHL (pSS-NHL+) from the United Kingdom Primary Sjögren's Syndrome Registry cohort. PSS-nonL patients were stratified into low risk (LR), moderate risk (MR) and high risk (HR) groups according to the lymphoma risk score proposed by Fragkioudaki et al. Differences in serum CXCL13 levels among groups were analysed using the Wilcoxon method. Also, changes in serum CXCL13 over a time period of at least 1 year and a median 4 years were assessed for 200 pSS-nonL and 8 pSS-NHL+ patients. In addition, associations of serum CXCL13 with B-cell and inflammatory markers were investigated by correlation analyses and logistic regression. Serum CXCL13 levels were higher in all pSS groups compared to controls (p < 0.0001), and in pSS-NHL+ compared to pSS-nonL patients (p = 0.0204). LR patients had lower CXCL13 levels than MR patients (p < 0.0001) and pSS-NHL+ patients (p = 0.0008). CXCL13 levels remained stable over the study period for all pSS groups. CXCL13 was associated (p < 0.0005) with Immunoglobulin G (IgG), B-cell activating factor, β2 microglobulin, combined free light chains, κ and λ light chains, anti-Ro/SSA, anti-La/SSB, and erythrocyte sedimentation rate. IgG and C3 controlled for age and gender were significantly associated with NHL risk in pSS. Serum CXCL13 levels were elevated in pSS-NHL+ and MR patients compared to LR patients and remained stable over time. Further study is required to investigate the role of CXCL13 in pSS-associated NHL risk.
33333049 Nimbolide exerts protective effects in complete Freund's adjuvant induced inflammatory art 2021 Feb 1 AIM: Activation of transmembrane Notch-1 receptors through inflammatory cytokines is highly regulated by STAT-3 and NF-κB phosphorylation. Nimbolide (NMB) exhibits potent anti-inflammatory, anti-fibrotic, anticancer activities by targeting various pathways. Here, we have investigated the effect of NMB in regulation of STAT-3/NF-κB/Notch-1 axis in complete Freund's adjuvant (CFA) induced inflammatory arthritis (IA) model. MAIN METHODS: The anti-inflammatory and anti-arthritic activity of NMB was evaluated both in vitro (IL-1β stimulated HIG-82 synovial fibroblasts) and in vivo (CFA induced rat model of IA) models. In vitro anti-arthritic activity was assessed by anti-migratory effect, while in vivo effects were evaluated through radiological and histological analysis. The effect of NMB on STAT-3, NF-κB, Notch-1 signaling pathways and proinflammatory cytokines were studied using western blot, immunohistochemistry and ELISA methods. Key findings NMB attenuated the migration of synovial fibroblasts in vitro. It reduced the progression of arthritis as evidenced from the improved radiological and histological abnormalities in arthritic rats. NMB significantly suppressed the nitrosooxidative stress and levels of pro-inflammatory cytokines. NMB also exhibited remarkable protective activity against upregulation of MAPK, STAT-3 and NF-κB phosphorylation mediated Notch-1 signaling pathway in synovial tissue of arthritic rats. SIGNIFICANCE: NMB may have clinical therapeutic value in rheumatoid arthritis by inhibiting STAT-3/NF-κB/Notch-1 axis and also by reducing the levels of proinflammatory cytokines.
32050468 Physical and Psychological Factors Affecting Falls in Older Patients with Arthritis. 2020 Feb 9 As the population ages, falls are becoming one of the leading causes of morbidity and mortality. Joint disease (either osteoarthritis or rheumatoid arthritis) is a well-known predictor of falls, and these medical conditions increase in accordance with the aging population. This study aimed to describe individual, physical, and psychological characteristics between older adults with and without a fall history. Further, we aimed to identify statistically significant physical or psychological factors associated with falls by controlling individual variables. We analyzed data from the 2014 Survey of Living Conditions and Welfare Needs of Korean Older Adults. Adults aged 65 years or over with doctor-diagnosed joint disease were eligible. A total of 2707 women and 784 men (n = 3491) were enrolled. Of these, 1174 patients suffered a fall within a year (average number of falls = 2.4). We adopted individual variable-adjusted models and found that limited activities of daily living (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.04-1.87), fear of falling (OR 7.18, 95% CI 4.26-12.09), and depression (OR 1.28, 95% CI 1.09-1.50) significantly increased fall risks on logistic regression analysis. Our findings suggest that physical and psychological factors, especially the fear of falling, need to be addressed to prevent falls in elderly patients with arthritis.
33087015 Coexistence of acute poststreptococcal glomerulonephritis and acute rheumatic fever in a J 2020 Jul Although acute poststreptococcal glomerulonephritis (APSGN) and acute rheumatic fever (ARF) are well-known complications of group A streptococcus infection, concomitant occurrence of both diseases is rare. We report an 11-year-old Japanese girl with primary Sjögren's syndrome complicated by acute renal failure about 2 weeks after the onset of pharyngitis. Although histopathological findings of the kidney were not confirmative, APSGN was suggested by the spontaneous recovery of her renal function, typical latent period with high levels of antistreptolysin O and low serum levels of C3 but not of C4. In addition, cardiac hypomotility and regurgitation of the 4 valves progressed in the convalescent phase of APSGN, which was accompanied by elevation of serum C-reactive protein and plasma brain natriuretic peptide (BNP) levels. Myocarditis was suggested by delayed gadolinium-enhancement of cardiac walls on cardiac magnetic resonance imaging. She was diagnosed with APSGN and ARF and was treated with a combination of short course prednisolone and prophylactic penicillin G. There is no relapse of renal or cardiac symptoms during 6 years follow-up. Unexpected elevation of plasma BNP in a convalescent stage of APSGN suggests the development of ARF. Underlying Sjögren's syndrome (SS) may modify the histopathological findings and make it difficult to differentiate APSGN from CTD-associated nephritis such as lupus nephritis (LN) even by renal biopsy.
32896450 [Blepharospasm, dry eye and extractable nuclear antigen antibodies (French translation of 2020 Oct PURPOSE: The goal of this study is to determine a link between benign essential blepharospasm and Sjogren's syndrome by analyzing the presence of extractable nuclear antigens in this population. METHODS: Seventy-two patients with benign essential blepharospasm (BEB) were included in this study. We eliminated patients with hemifacial spasm or blepharospasm secondary to corneal pathology. We collected the values of the Schirmer I test and the results of the anti-SSA and anti-SSB antibodies. RESULTS: Our study included 72 patients (144 eyes) whose 62 women (86.1%). Mean age was 74.3 years±10.73. Average Schirmer I test was 3.14mm±4.00mm. Five women (8% of this female population) had positive anti-SSA and SSB antibodies. Their mean age was 65.66 years±13.24 whereas the negative antibody patients had an average age of 75.42±9.27. There was no significant difference between their Schimer I test and the Schirmer I of negative antibody population. CONCLUSION: This study illustrates the possible association between the presence of Sjögren's syndrome and the occurrence of a BEB justifying the search for anti-SSA and anti SSB in blepharospasm patients.
32669454 Mixed results with baricitinib in biological-resistant adult-onset Still's disease and und 2020 Jul This clinical case series describes our experience with the use of Janus kinase 1/2 inhibitor baricitinib in two patients suffering from refractory adult-onset Still's disease (AOSD) as well as in one case suffering from AOSD-like autoinflammatory disease in the context of myelodysplastic syndrome. All patients suffered from disease non-responsive to conventional Disease-modifying antirheumatic drugs (DMARDs) as well as biological therapies including interleukin (IL)-1 and IL-6 blockade, relying instead on high daily doses of prednisolone. We also report the first case of Pneumocystis jirovecii infection following baricitinib use.
31707561 Clonal relationship of marginal zone lymphoma and diffuse large B-cell lymphoma in Sjogren 2020 Mar The occurrence of diffuse large B-cell lymphoma (DLBCL) in the course of Sjogren's syndrome (SS) is considered to be equally related either to the development of DLBCL de novo or to the transformation from marginal zone lymphoma (MZL). However, the question of possible clonal relationship between MZL and DLBCL in the group of SS patients remains open. Here we present the data concerning 194 patients with lymphoma complicated SS followed up at Nasonova Research Institute of Rheumatology during the last 22 years. Molecular analysis of tumor cells was performed for 6 SS patients who had developed both MZL and DLBCL. To assess clonal relationship between each of the tumor pairs immunoglobulin heavy chain (IGH) gene rearrangements were identified according BIOMED-2 protocol by means of multiplex polymerase chain reaction followed by GeneScan fragment analysis. Despite different localization MZL and DLBCL were clonally related in five tumor pairs. The median time to transformation was 11 months (range 0-78 months). MZL and DLBCL were clonally related in most cases from our cohort of SS patients. No statistically significant difference in survival between patients with DLBCL transformed from MZL and patients with de novo DLBCL was found in the cohort of SS patients investigated.
31274159 CXCL13 as biomarker for histological involvement in Sjögren's syndrome. 2020 Jan 1 OBJECTIVES: SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres' formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres' activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation. The aim of this study was to evaluate the potential role of CXCL13 as a biomarker of SG pathology in two independent SS cohorts. METHODS: 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n = 60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n = 49). Both sera and matched minor SG biopsy were available. Sicca (n = 57) and healthy subjects' (n = 19) sera were used as control. RESULTS: CXCL13 serum level was higher in SS patients compared with controls. Correlations between its serum levels and a series of histomorphological parameters, including size of the aggregates and the presence germinal centres', were observed. CONCLUSION: Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies.
33148701 Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficien 2020 Nov 4 OBJECTIVES: To evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy. METHODS: SELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts ('non-responders') and at week 26 based on Clinical Disease Activity Index (CDAI) >10 ('incomplete-responders') without washout. RESULTS: A total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups. CONCLUSIONS: These observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.
32190559 Consensus approach for 3D joint space width of metacarpophalangeal joints of rheumatoid ar 2020 Feb BACKGROUND: Joint space assessment for rheumatoid arthritis (RA) by ordinal conventional radiographic scales is susceptible to floor and ceiling effects. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides superior resolution, and may detect earlier changes. The goal of this work was to compare existing 3D methods to calculate joint space width (JSW) metrics in human metacarpophalangeal (MCP) joints with HR-pQCT and reach consensus for future studies. Using the consensus method, we established reproducibility with repositioning as well as feasibility for use in second-generation HR-pQCT scanners. METHODS: Three published JSW methods were compared using datasets from individuals with RA from three research centers. A SPECTRA consensus method was developed to take advantage of strengths of the individual methods. Using the SPECTRA method, reproducibility after repositioning was tested and agreement between scanner generations was also established. RESULTS: When comparing existing JSW methods, excellent agreement was shown for JSW minimum and mean (ICC 0.987-0.996) but not maximum and volume (ICC 0.000-0.897). Differences were identified as variations in volume definitions and algorithmic differences that generated high sensitivity to boundary conditions. The SPECTRA consensus method reduced this sensitivity, demonstrating good scan-rescan reliability (ICC >0.911) except for minimum JSW (ICC 0.656). There was strong agreement between results from first- and second-generation HR-pQCT (ICC >0.833). CONCLUSIONS: The SPECTRA consensus method combines unique strengths of three independently-developed algorithms and leverages underlying software updates to provide a mature analysis to measure 3D JSW. This method is robust with respect to repositioning and scanner generations, suggesting its suitability for detecting change.