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Abstract: The Nevado–Filabride complex, the lowest complex in the Betic hinterland, forms a stack of Alpine nappes. The tectonic units consist of metasedimentary sequences whose ages are not well constrained. Gneiss bodies included in the sequences have been one of the few sources of geochronological data in this metamorphic complex. New radiometric data from U-Pb zircon dating on gneisses from the western Sierra Nevada confirm the presence of late Carboniferous intrusive rocks in the Betic hinterland. These results, combined with available data from the literature and a detailed structural analysis, suggest that the gneisses represent a single late Variscan magmatic event. Evidence for a close genetic relation between gneisses and tourmalinites is provided by field and petrographic observations, in conjunction with geochemical data, U-Pb zircon (314±7; 304±23Ma) and 40Ar/39Ar tourmaline (319.85±5.81; 317.85±3.67Ma) geochronology. A pre-late Carboniferous age for the basal formation of the Nevado–Filabride sequence can be inferred. The gneiss protolith and the graphite schist are considered to be the boron source and the precursor of the tourmalinites, respectively. Superposed tectonic units rather than a continuous Palaeozoic sequence is supported by the occurrence of Palaeozoic rocks at the top of the Nevado–Filabride complex. The nappe tectonics, as evidenced from the contractional character of the unit boundaries and the superposition of higher-grade on lower-grade metamorphic rocks, is additionally supported by the superposition of older on younger rocks as revealed from radiometric data. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases that are characterized by inflammation and muscle weakness. Dysferlinopathies are autosomal recessive limb-girdle muscular dystrophies caused by mutations in DYSF, which share a similar clinical presentation and histopathological inflammatory changes. To determine the sonographic differences between dysferlinopathies and IIM and whether these differences allow their classification. This observational, cross-sectional, and analytical study evaluated 20 muscles from 11 patients with dysferlinopathies and 11 patients with IIM. The patients were matched for age, sex, and disease duration. Clinical and laboratory variables were analyzed. Semi-quantitative scales were used to weigh the gray scale and power Doppler muscle abnormalities. Descriptive statistics were computed and discriminant analysis was performed to determine the ultrasound variables that best predicted the final diagnosis. Forty muscles were evaluated. Atrophy and higher Heckmatt scale scores were observed in patients with dysferlinopathies. A set of three muscles (biceps/brachialis, quadriceps, and gastrocnemius) had a diagnostic accuracy of 100% (sensitivity, 100%; specificity, 100%; canonical coefficient, 0.733 p < 0.001). A set of two formulas was used to classify both diseases correctly. In the present study, scanning of three muscle groups showed high diagnostic accuracy in differentiating dysferlinopathies from MII. Ultrasound can be used as an initial test in patients with suspected muscle disease or as an additional tool to support diagnosis in controversial cases., Competing Interests: Declarations. Ethical approval: The studies involving human participants were reviewed and approved by the Ethical and Research Committee of the Instituto Nacional de Rehabilitation. The patients/participants provided their written informed consent to participate in this study. Conflict of interest: The authors declare that they have NO affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Gender impact on phenotypical expression of Behçet's disease (BD) has been specifically investigated only in a few large-scale studies. The main goal of the study was to examine gender differences in a large cohort of patients affected by BD., Methods: Data were retrieved from the International AIDA Network Registry for BD. We assessed differences between males and females in terms of Behçet's syndrome Overall Damage Index (BODI), differences in the disease manifestations at onset and in the cumulative manifestations throughout disease course, as well as differences in the cardiovascular risk. Finally, predictive factors leading to major organ involvement were investigated., Results: In total, 1024 BD patients (567 males, 457 females) were enrolled in the study, with a male-to-female ratio of 1.24/1. Males displayed a significantly higher mean±SD BODI (1.92±2.09) at the last follow-up, compared to female patients (1.25±1.87) (P<0.0001). Uveitis (P<0.0001) and vascular involvement (P=0.0076) were significantly more frequent among males whereas female patients were significantly over-represented in arthralgia (P<0.0001), arthritis (P=0.00025), isolated headache (P<0.0001), central nervous system (CNS) involvement (P=0.040), and gastrointestinal involvement (P=0.00046). Regarding cardiovascular risk, no differences between the two groups emerged (P=0.617). Four variables were associated with the development of major organ involvement: male gender (OR=2.104, P=0.001), current treatment with biologic agents (OR=2.257, P=0.0003), origin from endemic countries (OR=2.661, P=0.0009), and disease duration (OR=1.002, P=0.024)., Conclusion: BD displays a more severe course among males. This subgroup develops more irreversible damage and presents more frequently ocular and vascular involvement during disease course. On the other hand, female patients are prone to experience articular involvement, headache, CNS and gastrointestinal involvement. These data suggest the existence of a gender-driven disease expression., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To evaluate the cardiac involvement in patients with Still's disease with a focus on myocarditis included in the multicenter AIDA (AutoInflammatory Disease Alliance) network Still's disease registry. To exploit the predictive factors for myocarditis in deriving a clinical risk patient profile for this severe manifestation., Methods: A multicenter observational study was built up assessing consecutive patients with Still's disease characterized by the cardiac involvement among those included in the AIDA Network Still's Disease Registry. The cardiac involvement was defined according to the presence of pericarditis, tamponade, myocarditis, and/or aseptic endocarditis., Results: In total, 73 patients with Still's disease and cardiac involvement were assessed (mean age 36.3±19.9 years, 42.5% male sex); out of them, 21.9% were children. The most common cardiac manifestation was the pericarditis in 90.4% of patients, 26.0% presented with myocarditis, and less frequently endocarditis (2.7%) and tamponade (1.4%). Comparing clinical features of patients with myocarditis than others, significantly increased frequencies of skin rash, and pleuritis as well as higher values of systemic score were recognised. Furthermore, an enhanced mortality rate was registered in patients with myocarditis. In regression models, the skin rash and the systemic score independently predicted the myocarditis., Conclusion: The characteristics of patients with Still's disease and cardiac involvement were assessed in the AIDA network. The most common feature was the pericarditis but also a more severe clinical picture was reported in patients with myocarditis. The latter was associated with increased mortality rate and with higher systemic score, identifying patients to be carefully managed.

Anti-synthetase syndrome (AS) is a subset of idiopathic inflammatory myopathy (IIM) characterized by the presence of anti-aminoacyl-transfer RNA synthetase accompanied by myositis, interstitial lung disease and other clinical features. According to a recent multicentric study, 31% of AS patients present skin lesions compatible with dermatomyositis, but sclerodermiform features are rare. Therefore, we aimed to report the case of a patient with simultaneous diagnosis of AS, deep morphea, vasculitic neuropathy, and myelodysplastic syndrome and review the current literature regarding these uncommon associations. A 57 year old man with axial and symmetrical proximal muscle weakness, skin thickening and B symptoms, later diagnosed with PL7 + AS, deep morphea, myelodysplastic syndrome (MDS) and vasculitic neuropathy documented by histopathologic studies and immunologic assessments. Since both AS and deep morphea share the vasculopathic changes and type II interferon-induced inflammation, we hypothesize that they may share pathogenic mechanisms. The muscle biopsy of the patient was consistent with AS and showed focal neutrophil infiltration. The patient received intensive immunosuppressive therapy for AS and vasculitic neuropathy, with high dose steroids, intravenous immunoglobulin (IVIg) and rituximab. Nonetheless, he suffered an unfavorable evolution with a fatal outcome due to septic shock. Albeit sclerodermiform features are rare in patients with AS, we propose a pathogenic link among AS, deep morphea and the autoimmune/autoinflammatory signs of MDS. The vasculopathic changes along with the activation of the innate and adaptive immune system leading to the production of proinflammatory cytokines may have been one of the contributing factors for the coexisting diagnosis of the patient., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, the pathologic significance of these autoantibodies has been questioned due to the assumption that autoantibodies cannot enter living muscle cells. This study aims to investigate the validity of this assumption., Methods: Confocal immunofluorescence microscopy was employed to localise antibodies and other proteins of interest in myositis muscle biopsies. Bulk RNA sequencing was used to examine the transcriptomic profiles of 669 samples, including those from patients with myositis, disease controls and healthy controls. Additionally, antibodies from myositis patients were introduced into cultured myoblasts through electroporation, and their transcriptomic profiles were analysed using RNA sequencing., Results: In patients with myositis autoantibodies, antibodies accumulated inside myofibres in the same subcellular compartment as the autoantigen. Bulk RNA sequencing revealed that muscle biopsies from patients with autoantibodies targeting transcriptional regulators exhibited transcriptomic patterns consistent with dysfunction of the autoantigen. For instance, in muscle biopsies from patients with anti-PM/Scl autoantibodies recognising components of the nuclear RNA exosome complex, an accumulation of divergent transcripts and long non-coding RNAs was observed; these RNA forms are typically degraded by the nuclear RNA exosome complex. Introducing patient antibodies into cultured muscle cells recapitulated the transcriptomic effects observed in human disease. Further supporting evidence suggested that myositis autoantibodies recognising other autoantigens may also disrupt the function of their targets., Conclusions: This study demonstrates that, in myositis, autoantibodies are internalised into living cells, causing biological effects consistent with the disrupted function of their autoantigen., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Systemic lupus erythematosus (SLE) is an autoimmune disorder that often leads to kidney injury, known as lupus nephritis (LN). Although renal biopsy is the primary way to diagnose LN, it is invasive and not practical for regular monitoring. As an alternative, several groups have proposed urinary extracellular vesicles (uEVs) as potential biomarkers for LN, as recent studies have shown their significance in reflecting kidney-related diseases. As a result, we developed a flow cytometry approach that allowed us to determine that LN patients exhibited a significantly higher total uEV concentration compared to SLE patients without kidney involvement. Additionally, an analysis of different-sized uEV subsets revealed that microvesicles ranging from 0.3 to 0.5 μm showed the most promise for distinguishing LN. These findings indicate that evaluating uEV concentration and size distribution could be a valuable diagnostic and monitoring tool for LN, pending further validation in more comprehensive studies.

The coronavirus disease 2019 (COVID-19) survivors are frequently observed to present persistent symptoms constituting what has been called "post-acute COVID-19 syndrome" (PACS) or "long COVID-19". Some clinical risk factors have been identified to be associated with PACS development; however, specific mechanisms responsible for PACS pathology remain unknown. This study investigates clinical, immunological, and metabolomic risk factors associated with post-acute COVID-19 syndrome (PACS) in 51 patients, assessed 7-19 months after acute infection. Among the participants, 62.7% were male and 37.2% were female, with an average age of 47.8 years. At the follow-up, 37.2% met the criteria for PACS, revealing significant differences in immunological and metabolomic profiles at the time of acute infection. Patients with PACS were characterized by elevated levels of mature low-density granulocytes (LDGs), interleukin-8 (IL-8), pyruvate, pseudouridine, and cystine. Baseline multivariate analysis showed increased pyruvate and decreased alpha tocopherol levels. At follow-up, there was a decrease in absolute B lymphocytes and an increase in non-classical monocytes and 3-hydroxyisovaleric acid levels. These findings suggest that specific immunological and metabolomic markers during acute infection can help identify patients at higher risk of developing persistent PACS.

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune disorders characterized by progressive muscle weakness and the histopathologic findings of inflammatory infiltrates in muscle tissue. Although their pathogenesis remains indefinite, the association of autoantibodies with clinical manifestations and the evidence of high effectiveness of depleting therapies suggest that B cells could be implicated. Therefore, we explored the landscape of peripheral B cells in this disease by multiparametric flow cytometry, finding significant numerical decreases in memory and double-negative subsets, as well as an expansion of the naive compartment relative to healthy controls, that contribute to defining disease-associated B-cell subset signatures and correlating with different clinical features of patients. Additionally, we determined the potential value of these subsets as diagnostic biomarkers, thus positioning B cells as neglected key elements possibly participating in idiopathic inflammatory myopathy onset or development., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Purpose: The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet's disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown., Methods: Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time., Results: Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed ( p  = 0.465). With regard to VA, a significant difference was detected in median BCVA ( p  = 0.046), which was not maintained after Bonferroni correction ( p  = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD ( p  = 0.025). No differences emerged in the occurrence of macular edema ( p  = 0.99)., Conclusions: Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features.