Rheumatology (Oxford, England)最新文献

{"title":"Clinical vignette: paraneoplastic diffuse systemic sclerosis.","authors":"Katarzyna Nowak, Gary Wright","doi":"10.1093/rheumatology/keac106","DOIUrl":"https://doi.org/10.1093/rheumatology/keac106","url":null,"abstract":"","PeriodicalId":379078,"journal":{"name":"Rheumatology (Oxford, England)","volume":" ","pages":"e323"},"PeriodicalIF":5.5,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39932142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disparities in the prevalence of clinical features between systemic juvenile idiopathic arthritis and adult-onset Still's disease.","authors":"Piero Ruscitti,&nbsp;Valentina Natoli,&nbsp;Alessandro Consolaro,&nbsp;Roberta Caorsi,&nbsp;Silvia Rosina,&nbsp;Gabriella Giancane,&nbsp;Roberta Naddei,&nbsp;Ilenia Di Cola,&nbsp;Claudia Di Muzio,&nbsp;Onorina Berardicurti,&nbsp;Daniela Iacono,&nbsp;Ilenia Pantano,&nbsp;Gelsomina Rozza,&nbsp;Silvia Rossi,&nbsp;Ludovico De Stefano,&nbsp;Silvia Balduzzi,&nbsp;Antonio Vitale,&nbsp;Francesco Caso,&nbsp;Luisa Costa,&nbsp;Marcella Prete,&nbsp;Luca Navarini,&nbsp;Annamaria Iagnocco,&nbsp;Fabiola Atzeni,&nbsp;Giuliana Guggino,&nbsp;Federico Perosa,&nbsp;Luca Cantarini,&nbsp;Bruno Frediani,&nbsp;Carlomaurizio Montecucco,&nbsp;Francesco Ciccia,&nbsp;Paola Cipriani,&nbsp;Marco Gattorno,&nbsp;Roberto Giacomelli,&nbsp;Angelo Ravelli","doi":"10.1093/rheumatology/keac027","DOIUrl":"https://doi.org/10.1093/rheumatology/keac027","url":null,"abstract":"<p><strong>Objective: </strong>To compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still's disease (AOSD).</p><p><strong>Methods: </strong>The clinical charts of consecutive patients with sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered.</p><p><strong>Results: </strong>A total of 166 patients (median age at diagnosis 5 years) with sJIA and 194 patients with AOSD (median age at diagnosis 41 years) were included. The frequency of fever, rash, arthralgia, abdominal pain, MAS, parenchymal lung disease and increased acute phase reactants and ferritin were comparable between the two cohorts. Patients with sJIA had a higher prevalence of arthritis, whereas patients with AOSD had experienced leucocytosis and extra-articular organ involvement more frequently. Patients with AOSD were given more commonly low-dose corticosteroids, whereas biologic DMARDs were administered first-line more frequently in patients with sJIA.</p><p><strong>Conclusion: </strong>We found remarkable disparities in the prevalence of clinical manifestations between the two illnesses, which may partly depend on their classification by different criteria.</p>","PeriodicalId":379078,"journal":{"name":"Rheumatology (Oxford, England)","volume":" ","pages":"4124-4129"},"PeriodicalIF":5.5,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39735586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical features and immune-related protein patterns of anti-MDA5 positive clinically amyopathic dermatomyositis Dutch patients.","authors":"Marjolein P M Hensgens,&nbsp;Eveline M Delemarre,&nbsp;Julia Drylewicz,&nbsp;Mareye Voortman,&nbsp;Roline M Krol,&nbsp;Virgil A S H Dalm,&nbsp;Jelle R Miedema,&nbsp;Ivo Wiertz,&nbsp;Jan Grutters,&nbsp;Maarten Limper,&nbsp;Stefan Nierkens,&nbsp;Helen L Leavis","doi":"10.1093/rheumatology/keac030","DOIUrl":"https://doi.org/10.1093/rheumatology/keac030","url":null,"abstract":"<p><strong>Objectives: </strong>The presence of melanoma differentiation-associated protein 5 (MDA5) antibodies in patients with DM is associated with the development of a rapidly progressive interstitial lung disease (RPILD), unresponsive to conventional treatment. We characterize patients and provide more insight into potential biomarkers to identify patients with RPILD.</p><p><strong>Methods: </strong>Patients diagnosed with anti-MDA5 positive DM between December 2015 and November 2017 were included in this study. Clinical data were retrospectively retrieved from medical records. A total of 180 immune-related markers were measured in sera of 16 patients and 15 healthy controls using proximity extension assay-based technology.</p><p><strong>Results: </strong>Twenty patients were included, with a median time from symptoms till diagnosis of 4 months. All patients had clinically amyopathic DM. Interstitial lung disease (ILD) was present at diagnosis in 94% of the patients, 45% presented with RPILD. The mortality rate was 35% within 4 months after diagnosis and respiratory failure was the main cause of death in these patients. Furthermore, unsupervised analysis revealed that patients with RPILD show clearly different inflammatory serum profiles than healthy controls. In addition, in comparison to healthy controls, the IFN, IL1, IL10 and IL18 signalling pathways are different regulated in anti-MDA5 positive patients.</p><p><strong>Conclusion: </strong>In this Dutch anti-MDA5 positive clinically amyopathic DM (CADM) cohort, one-third of the patients died due to RPILD soon after diagnosis, which underlines the severity of this disease. In addition, we have found several possible pathways that are differentially regulated in RPILD vs no RPILD DM and healthy controls. These markers await further validation before clinical use.</p>","PeriodicalId":379078,"journal":{"name":"Rheumatology (Oxford, England)","volume":" ","pages":"4087-4096"},"PeriodicalIF":5.5,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39836767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning algorithms for magnetic resonance imaging of inflammatory sacroiliitis in axial spondyloarthritis.","authors":"Karina Ying Ying Lin,&nbsp;Cao Peng,&nbsp;Kam Ho Lee,&nbsp;Shirley Chiu Wai Chan,&nbsp;Ho Yin Chung","doi":"10.1093/rheumatology/keac059","DOIUrl":"https://doi.org/10.1093/rheumatology/keac059","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to develop a deep learning algorithm for detection of active inflammatory sacroiliitis in short tau inversion recovery (STIR) sequence MRI.</p><p><strong>Methods: </strong>A total of 326 participants with axial SpA, and 63 participants with non-specific back pain (NSBP) were recruited. STIR MRI of the SI joints was performed and clinical data were collected. Region of interests (ROIs) were drawn outlining bone marrow oedema, a reliable marker of active inflammation, which formed the ground truth masks from which 'fake-colour' images were derived. Both the original and fake-colour images were randomly allocated into either the training and validation dataset or the testing dataset. Attention U-net was used for the development of deep learning algorithms. As a comparison, an independent radiologist and rheumatologist, blinded to the ground truth masks, were tasked with identifying bone marrow oedema in the MRI scans.</p><p><strong>Results: </strong>Inflammatory sacroiliitis was identified in 1398 MR images from 228 participants. No inflammation was found in 3944 MRI scans from 161 participants. The mean sensitivity of the algorithms derived from the original dataset and fake-colour image dataset were 0.86 (0.02) and 0.90 (0.01), respectively. The mean specificity of the algorithms derived from the original and the fake-colour image datasets were 0.92 (0.02) and 0.93 (0.01), respectively. The mean testing dice coefficients were 0.48 (0.27) for the original dataset and 0.51 (0.25) for the fake-colour image dataset. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the algorithms using the original dataset and the fake-colour image dataset were 0.92 and 0.96, respectively. The sensitivity and specificity of the algorithms were comparable with the interpretation by a radiologist, but outperformed that of the rheumatologist.</p><p><strong>Conclusion: </strong>An MRI deep learning algorithm was developed for detection of inflammatory sacroiliitis in axial SpA.</p>","PeriodicalId":379078,"journal":{"name":"Rheumatology (Oxford, England)","volume":" ","pages":"4198-4206"},"PeriodicalIF":5.5,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39878380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning using genetic and clinical data identifies a signature that robustly predicts methotrexate response in rheumatoid arthritis.","authors":"Lee Jin Lim,&nbsp;Ashley J W Lim,&nbsp;Brandon N S Ooi,&nbsp;Justina Wei Lynn Tan,&nbsp;Ee Tzun Koh,&nbsp;Samuel S Chong,&nbsp;Chiea Chuen Khor,&nbsp;Lisa Tucker-Kellogg,&nbsp;Caroline G Lee,&nbsp;Khai Pang Leong","doi":"10.1093/rheumatology/keac032","DOIUrl":"https://doi.org/10.1093/rheumatology/keac032","url":null,"abstract":"<p><strong>Objective: </strong>To develop a hypothesis-free model that best predicts response to MTX drug in RA patients utilizing biologically meaningful genetic feature selection of potentially functional single nucleotide polymorphisms (pfSNPs) through robust machine learning (ML) feature selection methods.</p><p><strong>Methods: </strong>MTX-treated RA patients with known response were divided in a 4:1 ratio into training and test sets. From the patients' exomes, potential features for classifier prediction were identified from pfSNPs and non-genetic factors through ML using recursive feature elimination with cross-validation incorporating the random forest classifier. Feature selection was repeated on random subsets of the training cohort, and consensus features were assembled into the final feature set. This feature set was evaluated for predictive potential using six ML classifiers, first by cross-validation within the training set, and finally by analysing its performance with the unseen test set.</p><p><strong>Results: </strong>The final feature set contains 56 pfSNPs and five non-genetic factors. The majority of these pfSNPs are located in pathways related to RA pathogenesis or MTX action and are predicted to modulate gene expression. When used for training in six ML classifiers, performance was good in both the training set (area under the curve: 0.855-0.916; sensitivity: 0.715-0.892; and specificity: 0.733-0.862) and the unseen test set (area under the curve: 0.751-0.826; sensitivity: 0.581-0.839; and specificity: 0.641-0.923).</p><p><strong>Conclusion: </strong>Sensitive and specific predictors of MTX response in RA patients were identified in this study through a novel strategy combining biologically meaningful and machine learning feature selection and training. These predictors may facilitate better treatment decision-making in RA management.</p>","PeriodicalId":379078,"journal":{"name":"Rheumatology (Oxford, England)","volume":" ","pages":"4175-4186"},"PeriodicalIF":5.5,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39570832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab.","authors":"Maike H M Wientjes,&nbsp;Titia M G Gijzen,&nbsp;Nathan den Broeder,&nbsp;Karien Bloem,&nbsp;Annick de Vries,&nbsp;Bart J F van den Bemt,&nbsp;Alfons A den Broeder,&nbsp;Lise M Verhoef","doi":"10.1093/rheumatology/keac024","DOIUrl":"https://doi.org/10.1093/rheumatology/keac024","url":null,"abstract":"<p><strong>Objectives: </strong>The REDO trial (REtreatment with Rituximab in RhEumatoid arthritis: Disease Outcome after Dose Optimisation) showed that ultra-low-dose rituximab (500 mg or 200 mg) was similarly effective to a 1000 mg dosage in the majority of RA patients. This pre-planned secondary analysis investigated (1) associations between rituximab dosage, drug levels, anti-drug antibodies (ADAs) and B-cell counts and (2) the predictive value of pharmacokinetic and pharmacodynamic parameters, and of patient, disease and treatment characteristics in relation to response to ultra-low-dose rituximab.</p><p><strong>Methods: </strong>For 140 RA patients from the REDO trial, differences in drug levels, ADAs and B-cell counts were examined at baseline, and at 3 and 6 months after dosing. Treatment response was defined as absence of flare and no extra rituximab or >1 glucocorticoid injection received during follow-up. The association between potential predictors and response was investigated using logistic regression analyses.</p><p><strong>Results: </strong>Lower doses of rituximab resulted in lower drug levels but did not significantly affect ADA levels or B-cell counts, and 3 (10.7%), 12 (20.7%) and 7 (13.0%) patients failed to meet the response criteria in, respectively, the 1000 mg, 500 mg and 200 mg dosage groups. Drug levels, ADAs, B-cell counts, and patient, disease and treatment characteristics were not predictive for response to ultra-low-dose rituximab.</p><p><strong>Conclusion: </strong>The results of this study further support the hypothesis that continued treatment with 500 or 200 mg rituximab is similarly effective to a 1000 mg dosage in RA patients doing well on rituximab. These results, combined with lack of finding a clinical dose-response relationship in the original REDO study, suggest that 200 mg rituximab is not yet the lowest effective rituximab retreatment dose in RA.</p>","PeriodicalId":379078,"journal":{"name":"Rheumatology (Oxford, England)","volume":" ","pages":"3974-3980"},"PeriodicalIF":5.5,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39692235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of biologic and targeted-synthetic disease-modifying antirheumatic drug use in rheumatoid arthritis in Australia.","authors":"Ashley Fletcher,&nbsp;Marissa Lassere,&nbsp;Lyn March,&nbsp;Catherine Hill,&nbsp;Claire Barrett,&nbsp;Graeme Carroll,&nbsp;Rachelle Buchbinder","doi":"10.1093/rheumatology/keac048","DOIUrl":"https://doi.org/10.1093/rheumatology/keac048","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to describe treatment patterns in RA, including the frequency and reasons for switching or stopping biologic and targeted synthetic DMARDs (b/tsDMARDs).</p><p><strong>Methods: </strong>The reasons for switching or stopping b/tsDMARDs were extracted from the Australian Rheumatology Association Database (ARAD) from 2003 to 2018 for RA participants. Switching patterns for each b/tsDMARD and time on first-, second- and third-line b/tsDMARDs were evaluated using Sankey diagrams and survival methods.</p><p><strong>Results: </strong>A total of 2839 participants were included in the analysis. The first-line b/tsDMARDs were etanercept (n = 1414), adalimumab (n = 1024), infliximab (n = 155), golimumab (n = 98), abatacept (n = 66), certolizumab (n = 38), tocilizumab (n = 21) and tofacitinib (n = 23). Of those starting first-, second- and third-line biologic therapy, 24.0%, 31.8% and 24.4% switched to another b/tsDMARD within 12 months, respectively. Inefficacy or adverse effects were the most common reasons for stopping therapy, irrespective of line of treatment. Compared with first-line etanercept, participants were more likely to stop adalimumab [Hazard ratio (HR) 1.16, 95% CI: 1.04, 1.29] and infliximab (HR 1.77, 95% CI: 1.46, 2.16). No differences were seen for other b/tsDMARDs. For second-line therapies compared with etanercept, the risk of stopping was lower for tocilizumab (HR 0.41, 95% CI: 0.25, 0.70), rituximab (HR 0.51, 95% CI: 0.30, 0.85) and tofacitinib (HR 0.29, 95% CI: 0.15, 0.57). Participants taking rituximab, tocilizumab and tofacitinib were also less likely to stop third-line therapy in comparison with participants taking etanercept.</p><p><strong>Conclusions: </strong>Switching between b/tsDMARDs was common among ARAD participants with RA, most commonly due to inefficacy or adverse effects. Durability of exposure and reasons for switching varied between b/tsDMARDs.</p>","PeriodicalId":379078,"journal":{"name":"Rheumatology (Oxford, England)","volume":" ","pages":"3939-3951"},"PeriodicalIF":5.5,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/72/keac048.PMC9536792.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39732733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological characteristics of DISH in patients with OPLL and its association with high-sensitivity CRP: inflammatory DISH.","authors":"Tran Canh Tung Nguyen,&nbsp;Yasuhito Yahara,&nbsp;Taketoshi Yasuda,&nbsp;Shoji Seki,&nbsp;Kayo Suzuki,&nbsp;Kenta Watanabe,&nbsp;Hiroto Makino,&nbsp;Katsuhiko Kamei,&nbsp;Kanji Mori,&nbsp;Yoshiharu Kawaguchi","doi":"10.1093/rheumatology/keac051","DOIUrl":"https://doi.org/10.1093/rheumatology/keac051","url":null,"abstract":"<p><strong>Objectives: </strong>To characterize and clarify evidence as to whether the ectopic bone formations of DISH in patients with ossification of the posterior longitudinal ligament (OPLL) are caused by inflammatory or degenerative processes.</p><p><strong>Methods: </strong>Whole-spine CT and serum high-sensitivity CRP (hs-CRP) levels were obtained from 182 cervical OPLL patients (DISH+, n = 104; DISH-, n = 78). In the DISH+ group, ectopic bone formations were categorized into Flat and Jaggy types, then further divided into three subgroups: group 1 (Jaggy-dominant pattern), group 2 (Equivalence of pattern) and group 3 (Flat-dominant pattern). Data were compared between the DISH+ and DISH- groups, and among the three subgroups.</p><p><strong>Results: </strong>The upper thoracic spine was most affected by the Flat type, whereas the Jaggy type was more frequent in the middle and lower thoracic regions. There was no difference in hs-CRP levels between the DISH+ and DISH- groups. Among the three subgroups, hs-CRP levels in group 3 [mean (s.d.) 0.16 (0.09) mg/dl] were significantly higher than in group 1 [0.04 (0.02) mg/dl] and group 2 [0.08 (0.06) mg/dl]. Higher levels of hs-CRP were associated with a greater number of vertebral units with Flat-type formations (β = 0.691, P < 0.0001) and with a lesser number of vertebral units with Jaggy-type formations (β = -0.147, P = 0.036).</p><p><strong>Conclusion: </strong>The Flat type in DISH might be caused by an inflammatory pathogenesis rather than a degenerative process presented in the Jaggy type.</p>","PeriodicalId":379078,"journal":{"name":"Rheumatology (Oxford, England)","volume":" ","pages":"3981-3988"},"PeriodicalIF":5.5,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39740211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of 18F-fluorodeoxyglucose positron emission tomography to standardize clinical trial recruitment in Takayasu's arteritis.","authors":"Kaitlin A Quinn,&nbsp;Hugh D Alessi,&nbsp;Cristina Ponte,&nbsp;Emily Rose,&nbsp;Mark A Ahlman,&nbsp;Christopher Redmond,&nbsp;Yiming Luo,&nbsp;Ertugrul Cagri Bolek,&nbsp;Carol A Langford,&nbsp;Peter A Merkel,&nbsp;Peter C Grayson","doi":"10.1093/rheumatology/keac021","DOIUrl":"https://doi.org/10.1093/rheumatology/keac021","url":null,"abstract":"<p><strong>Objectives: </strong>To assess whether data from 18F-fluorodeoxyglucose (FDG) PET should be incorporated into eligibility criteria for clinical trials in Takayasu's arteritis (TAK).</p><p><strong>Methods: </strong>The study was conducted in two parts. Part one was an international online survey among physicians with experience managing TAK to determine, using clinical vignettes, whether FDG-PET data influence decisions about enrolment in trials. Part two used patient data from an observational cohort study in TAK to assess agreement regarding decisions about enrolment into trials, based on clinical assessment with and without incorporation of FDG-PET data.</p><p><strong>Results: </strong>In part one, 68 physicians responded to the survey. Most physicians had used FDG-PET to diagnose TAK (82%) or monitor disease activity (66%). In vignettes representing active clinical disease, FDG-PET findings increased physician confidence in disease assessment and reduced outlier assessments. The greatest variability in decisions regarding enrolment into trials was observed in vignettes representing constitutional symptoms alone and elevated acute-phase reactants. In these cases, FDG-PET findings influenced decisions about enrolment and improved physician confidence. In multivariable models, FDG-PET findings were 1.29 times more strongly associated with enrolment decisions compared with levels of acute-phase reactants. In part two, incorporation of FDG-PET data significantly improved agreement about enrolment decisions between raters [inter-rater reliability (IRR) = 0.68 (95% CI 0.67, 0.69) to IRR = 0.88 (95% CI 0.87, 0.89); P < 0.01].</p><p><strong>Conclusions: </strong>Incorporation of FDG-PET data into assessment of TAK influences decisions about enrolment of patients into trials, improves physician confidence about clinical assessment and could help reduce variability in study populations. Future trials in TAK should consider incorporating FDG-PET data into eligibility criteria.</p>","PeriodicalId":379078,"journal":{"name":"Rheumatology (Oxford, England)","volume":" ","pages":"4047-4055"},"PeriodicalIF":5.5,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536789/pdf/keac021.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39815560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbamylation of β2-glycoprotein I generates new autoantigens for antiphospholipid syndrome: a new tool for diagnosis of 'seronegative' patients.","authors":"Antonella Capozzi,&nbsp;Simona Truglia,&nbsp;Brigitta Buttari,&nbsp;Serena Recalchi,&nbsp;Gloria Riitano,&nbsp;Valeria Manganelli,&nbsp;Silvia Mancuso,&nbsp;Cristiano Alessandri,&nbsp;Agostina Longo,&nbsp;Vincenzo Mattei,&nbsp;Elisabetta Profumo,&nbsp;Tina Garofalo,&nbsp;Roberta Misasi,&nbsp;Fabrizio Conti,&nbsp;Maurizio Sorice","doi":"10.1093/rheumatology/keac045","DOIUrl":"https://doi.org/10.1093/rheumatology/keac045","url":null,"abstract":"<p><strong>Objectives: </strong>Antiphospholipid syndrome (APS) is a prothrombotic condition defined by recurrent thrombosis, pregnancy complications and circulating antiphospholipid antibodies (aPL), including anti-β2-glycoprotein I (β2-GPI). In clinical practice it is possible to find patients with APS persistently negative for the aPL tests according to Sydney criteria ('seronegative APS', SN-APS). Recently, several autoimmune responses have been described as a consequence of post-translational modifications of their target autoantigens. This study was undertaken to test carbamylated-β2-GPI (Carb-β2-GPI) as a new autoantigen of APS.</p><p><strong>Methods: </strong>β2-GPI was carbamylated by potassium cyanate and used to investigate its effect on monocyte-derived dendritic cell (moDC) phenotype and function. Sera from 114 SN-APS patients, 60 APS, 20 patients with RA, 20 non-APS thrombosis and 50 healthy donors were analysed for anti-Carb-β2-GPI by ELISA.</p><p><strong>Results: </strong>Carb-β2-GPI is able to activate moDCs, inducing upregulation of CD80, CD86 and CD40, activation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase and nuclear factor-κB, and IL-12p70 release. Serological results showed that both 37/114 SN-APS (32.46%) and 23/60 APS (38.33%) patients resulted positive for anti-Carb-β2-GPI. Interestingly, SN-APS patients who tested positive for anti-Carb-β2-GPI showed a higher prevalence of thrombocytopenia (P = 0.04, likelihood positive ratio of 3.9).</p><p><strong>Conclusion: </strong>Data obtained from both functional tests on moDCs and immunological approaches prompted identification of Carb-β2-GPI as a 'new' antigenic target in APS. In particular, anti-Carb-β2-GPI revealed a potential usefulness in identification of a significant proportion of SN-APS patients. Moreover, since patients who tested positive for anti-Carb-β2-GPI reported a high risk of thrombocytopenia, this test may be considered a suitable approach in the clinical evaluation of SN-APS.</p>","PeriodicalId":379078,"journal":{"name":"Rheumatology (Oxford, England)","volume":" ","pages":"4187-4197"},"PeriodicalIF":5.5,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39757914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}