Miguel A. González-Gay

ObjectiveThe CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an “ad-interim” study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity.

The term metabolic syndrome (MetS) encompasses a cluster of risk factors such as central obesity, high blood pressure, impaired fasting glucose, high triglycerides, and low high- density lipoprotein cholesterol (HDL-C), all of which are specific to cardiovascular (CV) disease.1 MetS is frequently observed in patients with rheumatoid arthritis (RA).2,3 In this regard, MetS abnormalities increase the risk of CV disease in these patients.4,5

Mean platelet volume (MPV), which represents the average platelet size in femtoliters, has emerged as a reliable biomarker in several systemic and chronic disorders. However, its relationship with disease characteristics in large series of patients with systemic lupus erythematosus (SLE) has not been exhaustively studied to date. In the present work, we aimed to analyze how disease characteristics, including disease activity and cumulative damage, relate to MPV in a well-characterized series of SLE patients. In total, 179 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood counts including MPV were assessed. Linear multivariable analysis was performed to evaluate the relationship between MPV and SLE disease characteristics, including composite scores of disease activity and damage. MPV was significantly lower in patients with SLE compared to controls after multivariable analysis (beta coefficient, −0.7 [95% confidence interval, −1.1 to −0.3)] fL, p < 0.001). Although the SLEDAI disease activity index was not related to MPV, the SLICC score measuring cumulative disease damage was significantly associated with lower MPV values after adjustment for covariates. Elements of the SLICC score that were associated with lower MPV levels were those pertaining to the kidney, peripheral vascular, and musculoskeletal manifestations of the disease. In conclusion, MPV is lower in patients with SLE compared to matched controls. This MPV downregulation is primarily due to the renal, peripheral vascular and musculoskeletal manifestations of the disease. MPV may represent a biomarker of accrual …

ObjectiveTo establish the predictive value of the QRESEARCH risk estimator version 3 (QRISK3) algorithm in identifying Spanish patients with ankylosing spondylitis (AS) at high risk of cardiovascular (CV) events and CV mortality. We also sought to determine whether to combine QRISK3 with another CV risk algorithm: the traditional SCORE, the modified SCORE (mSCORE) EULAR 2015/2016 or the SCORE2 may increase the identification of AS patients with high-risk CV disease.MethodsInformation of 684 patients with AS from the Spanish prospective CARdiovascular in ReuMAtology (CARMA) project who at the time of the initial visit had no history of CV events and were followed in rheumatology outpatient clinics of tertiary centers for 7.5 years was reviewed. The risk chart algorithms were retrospectively tested using baseline data.ResultsAfter 4,907 years of follow-up, 33 AS patients had experienced CV events …

Several retrospective multicentre open-label studies [1, 2] and randomized controlled trials [3, 4] have demonstrated that the anti-IL-6 receptor antibody tocilizumab is safe and effective to induce disease remission and reduce relapses, yielding a strong glucocorticoid-sparing effect, in patients with Giant Cell Arteritis (GCA). However, in these studies patients were treated with high-dose glucocorticoids for at least 26weeks [3, 4]. In this regard, Muratore et al. reported the results of a prospective observational trial aimed at establishing the potential impact of tocilizumab monotherapy after ultrashortpulse glucocorticoids on clinical manifestations and vessel inflammation and damage in patients older than 50years with active, newly diagnosed disease (n= 9) or recurrent (n= 9) large vessel (LV)-GCA [5]. Fifteen of the 18 patients had symptoms of active vasculitis at inclusion, while the remaining 3 patients had relapsing …

Background To describe the effectiveness and safety of COVID-19 vaccine in a series of patients with rheumatoid arthritis (RA). Methods Retrospective single-center study of RA patients, fulfilling the ACR 1987 or ACR/EULAR 2010 classification criteria, that received first COVID-19 vaccine between December 2020 and October 2021, had post-vaccination serology and subsequent follow-up of at least 6 months in a university hospital. Vaccine effectiveness was evaluated by the serological response and the incidence of post-vaccine COVID-19, and safety by the incidence of adverse events (AE) and RA flares. Adjusted logistic and linear multivariate regression analyses were carried out with Stata® to identify factors associated with vaccine response. Results We included 118 patients with RA (87.2% women, age 65.4±11.6 years, evolution 12.0±9.6 years). 95.8% received complete vaccination schedule. Most patients (88.1%) developed adequate humoral immunogenicity, and the degree of serological response was significantly related to younger age and previous COVID-19 infection. After vaccination, 18.6% presented mild SARS-CoV-2 infection. Vaccine AE (19.5%) were mostly mild and inversely associated with age (OR 0.95). RA flares were anecdotal (1.7%) and inversely related to age (OR 0.95). Conclusion Our results suggest that COVID-19 vaccine induces adequate humoral immunogenicity, with an acceptable safety profile in RA patients.

Angiogenesis- and NETosis-related risk loci involved in giant cell arteritis susceptibility by a genome-wide association study - White Rose Research Online White Rose logo White Rose Research Online Home Search Browse Contact Angiogenesis- and NETosis-related risk loci involved in giant cell arteritis susceptibility by a genome-wide association study Borrego-Yaniz, G, Ortiz-Fernández, L, Madrid-Paredes, A et al. (49 more authors) (Accepted: 2024) Angiogenesis- and NETosis-related risk loci involved in giant cell arteritis susceptibility by a genome-wide association study. The Lancet Rheumatology. ISSN 2665-9913 (In Press) Metadata Item Type: Article Authors/Creators: Borrego-Yaniz, G Ortiz-Fernández, L Madrid-Paredes, A Kerick, M Hernández-Rodríguez, J Mackie, SL Vaglio, A Morgan, A ORCID logo https://orcid.org/0000-0003-1109-624X Castañeda, S Solans, R Mestre-Torres, J Khalidi, N Langford, …

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system, which includes the evaluation of its three pathways, relates to blood cell counts in a population of patients with SLE. New-generation functional assays of the classical, alternative, and lectin pathways of the complement system were conducted in 284 patients with SLE. Additionally, serum levels of inactive molecules (C1q, C2, C3, C4, factor D) and activated molecules (C3a), as well as regulators (C1-inhibitor and factor H), were evaluated. Complete blood cell counts were analyzed. Multivariable linear regression analysis was performed to study the relationship of hematological profiles with this full characterization of the complement system. After multivariable adjustments that included age, sex, SLICC-DI (damage), and SLEDAI (activity) scores, as well as the use of aspirin, prednisone, methotrexate, azathioprine, and mycophenolate mofetil, several relationships were observed between the C pathways and the individual products and blood cells profile. Lower values of C1q and C2 were associated with lower hemoglobin levels. Lower leukocyte counts showed significantly lower values of C4, C1 inhibitor, C3, factor D, and alternative pathway functional levels. Neutrophil counts showed significant negative relationships only with the alternative pathway and C1-inh. In the case of lymphocytes, associations were found, especially …

Biopsy-proven giant cell arteritis in an elderly woman diagnosed 11 years earlier with microscopic polyangiitis: two different vasculitis in the same patient separated in time. - Abstract - Europe PMC Sign in | Create an account https://orcid.org Europe PMC Menu About Tools Developers Help Contact us Helpdesk Feedback Twitter Blog Tech blog Developer Forum Europe PMC plus Search life-sciences literature (43,429,590 articles, preprints and more) Search Advanced search Feedback This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy. Abstract Full text Biopsy-proven giant cell arteritis in an elderly woman diagnosed 11 years earlier with microscopic polyangiitis: two different vasculitis in the same patient separated in time. Fernandez-Prado R 1 , García-Fernández A 2 , Avello …

Objective Adverse events during pregnancy are common in systemic lupus erythematosus (SLE). For this reason, EULAR recommends its management in specialized pregnancy clinics. Our aim is to report the 10-year experience of a pregnancy clinic in a tertiary center in Spain.Methods Retrospective study of patients with SLE followed up in a specialized pregnancy clinic at a tertiary center in Madrid, Spain, who attended the clinic from December 2012 to January 2023. Categorical variables were described as proportions and/or percentages, while continuous variables were shown as mean and standard deviation (SD) or median and interquartile range (IQR) when appropriate.Results 56 cases of pregnancy counselling’s in 38 patients with SLE were included. The main characteristics are reported in table 1. Preconception consultation was performed in 57.1% (32/56) of the cases since 42.9% (24/56) were already …

ObjectiveTo assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients.MethodsEvaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3).ResultsOver 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four …

Objective The biologic diagnosis of primary Sjögren disease (SjD) mainly relies on anti-Ro60/SSA antibodies, whereas the significance of anti-Ro52/TRIM21 antibodies currently remains unclear. The aim of this study was to characterize the clinical, serological, biologic, transcriptomic, and interferon profiles of patients with SjD according to their anti-Ro52/TRIM21 antibody status. Methods Patients with SjD from the European PRECISESADS (n = 376) and the Brittany Diagnostic Suspicion of primitive Sjögren's Syndrome (DIApSS); (n = 146) cohorts were divided into four groups: double negative (Ro52‾/Ro60‾), isolated anti-Ro52/TRIM21 positive (Ro52+), isolated anti-Ro60/SSA positive (Ro60+), and double-positive (Ro52+/Ro60+) patients. Clinical information; EULAR Sjögren Syndrome Disease Activity Index, a score representing systemic activity; and biologic markers associated with disease severity were evaluated. Transcriptome data obtained from whole blood by RNA sequencing and type I and II interferon signatures were analyzed for PRECISESADS patients. Results In the DIApSS cohort, Ro52+/Ro60+ patients showed significantly more parotidomegaly (33.3% vs 0%?11%) along with higher β2-microglobulin (P =0.0002), total immunoglobulin (P <0.0001), and erythrocyte sedimentation rate levels (P =0.002) as well as rheumatoid factor (RF) positivity (66.2% vs 20.8%?25%) compared to other groups. The PRECISESADS cohort corroborated these observations, with increased arthritis (P =0.046), inflammation (P =0.005), hypergammaglobulinemia (P <0.0001), positive RF (P <0.0001), leukopenia (P =0.004), and lymphopenia (P =0 …

Myositis classification criteria/G. Zanframundo et al. juvenile idiopathic inflammatory myoa pathies and their major subgroups (18). The authors identified different pitfalls in the criteria and suggested actions that a possible revision should take to overa come them. The focus is surely well directed, but we believe that some addia tional issues with these criteria need to be highlighted and hopefully addressed by the future revision. We believe that more emphasis should be addressed toward those disease forms presenting without muscular ina volvement, especially ILD. These casa es are not uncommon, considering that up to 20% of ASSD patients have no myositis (11), and myositis is not coma mon even in both Asian (21) and not Asian (22) patients with anti-MDA5 syndrome. At present, these patients can be easily classified as interstitial pneumonia with autoimmune features (IPAF)(23), but not as IIMs (18), dea spite these conditions are commonly considered amongst the myositis speca trum disorder (MSD). Even the action proposed in the scoping review (20), namely the inclusion of ILD among the criteria, seem insufficient to address this issue, unless ILD (and not just skin involvement) is also to be considered as a condition potentially related to a clinically amyopathic form. Furthermore, the current criteria (18) do not allow the classification of paa tients with short-term disease (< 6 months). This feature can impact the planning of clinical trials addressed to anti-MDA5 positive patients with rapa idly progressive (RP) ILD. In fact, RPILD is an early manifestation of the ana ti-MDA5 syndrome, mainly occurring in the first 2 months from disease onset …

Background & objectivesThis study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs’: TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction.Patients & methodsA total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on …

Glucocorticoids constitute the cornerstone of therapy in the management of polymyalgia rheumatica (PMR)[1]. Nevertheless, their use in a disease that affects people≥ 50 years of age is associated with significant morbidity [2]. This is closely related to the occurrence of frequent relapses when glucocorticoids are tapered [3], resulting in a prolonged duration of glucocorticoid treatment. Consequently, the efficacy of glucocorticoid-sparing agents in the management of PMR patients, in particular in those who have comorbidities or who experience relapses, is a matter of great interest. Although a recent study highlighted the role of the anti-IL-6 receptor sarilumab in sustaining remission and reducing the cumulative glucocorticoid dose in PMR patients with a relapse during glucocorticoid tapering [4], most studies on this issue have focused on the utility of conventional synthetic disease-modifying antirheumatic drugs …

Background. Oxidative stress has been involved in the pathogenesis of rheumatoid arthritis (RA). The serum malondialdehyde (MDA) level is a reliable biomarker of oxidative stress status. In the present work, we aimed to analyze how a comprehensive characterization of the disease characteristics in RA, including a lipid profile, insulin resistance, and subclinical atherosclerosis, relates to serum MDA levels. Methods. In a cross-sectional study that included 430 RA patients, serum MDA levels were evaluated. Multivariable analysis was performed to examine the relationship of MDA with disease activity scores and disease characteristics, including subclinical carotid atherosclerosis, a comprehensive lipid molecule profile, and indices of insulin resistance and beta cell function indices. Results. The erythrocyte sedimentation rate (ESR) showed a significant and positive relationship with MDA. However, this did not occur for other acute phase reactants such as C-reactive protein or interleukin-6. Although the DAS28-ESR score (Disease Activity Score in 28 joints) had a positive and significant association with MDA serum levels, other disease activity scores that do not use the erythrocyte sedimentation rate in their formula did not show a significant relationship with MDA. Other disease characteristics, such as disease duration and the existence of rheumatoid factor and antibodies against citrullinated protein, were not related to serum MDA levels. This also occurred for lipid profiles, insulin resistance indices, and subclinical carotid atherosclerosis, for which no associations with circulating MDA were found. Conclusions. The disease characteristics are …

The most critical forms of coronavirus disease 2019 (COVID-19) are associated with excessive activation of the inflammasome. Despite the COVID-19 impact on public health, we still do not fully understand the mechanisms by which the inflammatory response influences disease prognosis. Accordingly, we aimed to elucidate the role of polymorphisms in the key genes of the formation and signaling of the inflammasome as biomarkers of COVID-19 severity. For this purpose, a large and well-defined cohort of 377 COVID-19 patients with mild (n = 72), moderate (n = 84), severe (n = 100), and critical (n = 121) infections were included. A total of 24 polymorphisms located in inflammasome-related genes (NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, IL18, NFKB1, ATG16L1, and MIF) were genotyped in all of the patients and in the 192 healthy controls (HCs) (who were without COVID-19 at the time of and before the study) by RT-qPCR. Our results showed that patients with mild, moderate, severe, and critical COVID-19 presented similar allelic and genotypic distribution in all the variants studied. No statistically significant differences in the haplotypic distribution of NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, and ATG16L1 were observed between COVID-19 patients, who were stratified by disease severity. Each stratified group of patients presented a similar genetic distribution to the HCs. In conclusion, our results suggest that the inflammasome polymorphisms studied are not associated with the worsening of COVID-19.

Fibroblast growth factor 23 (FGF23), a hormone secreted by osteocytes and osteoblasts, is a major regulator of vitamin D and phosphate homeostasis. FGF23 has been associated with the disturbance of mineral homeostasis, and with kidney and cardiovascular diseases. Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect virtually any organ. In the present work, we set out to analyze the relationship of FGF23 with the expression of SLE, including patterns of activity, damage, and severity. A total of 284 well-characterized patients with SLE were recruited. Activity (SLEDAI), severity (Katz), and damage index (SLICC-DI) scores were determined. The serum levels of FGF23 were also assessed. Multivariable linear regression analysis was performed to study the relationship between disease characteristics and FGF23. FGF23 and 25(OH) vitamin D were negatively correlated. Furthermore, prednisone use was associated with higher circulating FGF23 after an adjustment for confounding factors. SLICC-DI was related to higher serum levels of FGF23 after a multivariable analysis. However, when the SLICC-DI index items and domains were analyzed separately, apart from proteinuria ≥3.5 gm/24 h, only the musculoskeletal domain, encompassing arthritis and osteoporosis, was significantly associated with higher serum levels of FGF23. In conclusion, an association is observed between elevated serum FGF23 levels and disease damage, particularly related to musculoskeletal complications and proteinuria, in patients with SLE.

Background Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents. Methods We searched 6 databases until January 2023 for phase 2–4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response. Results The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113–10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554–3.161, p < 0.001) for ACR70 compared to tocilizumab. Conclusion We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On …

IntroductionPolymyalgia rheumatica (PMR) has emerged as a relatively common condition in Western countries. Although the diagnosis is relatively straightforward in people over 50 years of age who complain of sudden onset of pain and stiffness in the shoulder and hip girdles along with elevation of biomarkers of inflammation, manifestations of polymyalgia can also occur in the context of different conditions. For this reason, a complete history and examination is required, including looking for symptoms and signs suggestive of giant cell arteritis (GCA).Areas coveredThe review describes when and how to identify PMR, as well as when to suspect the presence of associated GCA or multiple conditions mimicking PMR.Expert opinionPMR does not have a specific diagnostic test. For this reason, a thorough clinical history searching for clinical data of GCA is needed. Moreover, the possibility of other diseases …