Systemic sclerosis (SSc) is a chronic autoimmune disease with multi-organ involvement. Historically, SSc classification has focused on the type of skin involvement (limited versus diffuse); however, a growing evidence of organ-specific variability suggests the presence of more than two distinct subtypes. We propose a semi-supervised generative deep learning framework leveraging expert-driven definitions of organ-specific involvement and severity. We model SSc disease trajectories in the European Scleroderma Trials and Research (EUSTAR) database, containing 14,000 patients across 67,000 medical visits, and identify clinically meaningful subtypes to enhance patient stratification and prognosis. We systematically evaluate the model’s predictive accuracy, robustness to missing data, and clinical interpretability. We identified five patient clusters, separating patients based on the degree of organ involvement. Notably, a subset with limited skin involvement still showed high risks of lung and heart complications, underscoring the importance of data-driven methods and multi-organ models to complement established insights from clinical practice.

To evaluate the main outcomes of disease activity and their association with other measures of activity, damage, and quality of life in patients with idiopathic inflammatory myopathy (IIM) according to time since diagnosis and positivity to antisynthetase autoantibodies (ASAs). Cross-sectional multicenter study within the Spanish Myo-Spain registry. Cases were classified as incident (≤ 12 months since diagnosis) and prevalent. The main outcomes of disease activity were the Myositis Disease Activity Assessment visual analogue scale (MYOACT), the Manual Muscle Test 8 (MMT-8), physician global activity (PhGA), and extramuscular activity. Other measures of activity, damage, and quality of life included patient global disease activity, MYOACT muscular, creatine phosphokinase, Health Assessment Questionnaire, physician and patient global damage, global damage of the Myositis Damage Index, and the 12-item Short-Form Health Survey (SF-12). We analyzed associations using a multivariate generalized linear model and a simple linear regression model. A total of 554 patients with different diagnostic subgroups of IIM were included (136 incident and 418 prevalent cases), with 215 ASA-positive patients (58 incident and 157 prevalent cases). All measures of disease activity were higher in the incident cases (p < 0.05), except for MYOACT muscular and creatine phosphokinase, for which no differences were recorded in ASA-positive patients. No differences were found between incident and prevalent cases for measures of damage. Values for the physical component of the SF-12 were higher in the prevalent cases (p < 0.05). The multivariate model was initially significant overall for the main activity outcomes. Positivity to ASAs was positively and negatively associated with the MYOACT index and MMT-8, respectively (p < 0.05), although no association was recorded with PhGA and extramuscular activity. Prevalent cases were negatively associated with the main outcomes of activity, except with MMT-8, for which the association was positive (p < 0.05). The main activity outcomes validated in polymyositis and dermatomyositis could also be used in other subtypes of IIM, such as antisynthetase syndrome. Recent diagnosis is associated with greater disease activity, as assessed based on these activity outcomes. PhGA and extramuscular activity are not modified by ASA positivity, thus supporting their preferred use for assessing treatment response in IIM with ASAs.

OBJECTIVES:Systemic sclerosis (SSc) is a complex autoimmune disease characterized by microvascular damage, immune dysregulation, and tissue fibrosis. While lymphocyte-platelet (PLT) complexes have been implicated in autoimmune diseases, their role in SSc is not well understood. METHODS:In a study of 21 predominantly female SSc patients, 66.7 % had limited SSc (lcSSc), with anti-centromere antibodies (ACA) being the most common autoantibody pattern. We applied flow cytometry to analyze B cells with bound PLTs, enzyme-linked immunosorbent assay (ELISA) to determine plasma levels of activated PLT soluble factors, and co-culture assays to evaluate B cell cytokine secretion and plasma cell differentiation. RESULTS:SSc patients had a higher percentage of B cells, but not T cells, with bound PLTs compared to healthy donors (HD). Despite similar PLT counts, SSc patients showed higher plasmatic levels of P-selectin (CD62P), soluble CD40 ligand (sCD40L), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β). Plasma IL-10 levels were also higher in SSc patients, with increased intracellular IL-10 in B cells with bound PLTs. We observed an increased IL-10 production and plasma cell differentiation when B cells were co-cultured with PLTs, especially from SSc patients. B cells with bound PLTs were associated with calcinosis, digital ulcers, and ACA status, with no effect from previous corticosteroid or aspirin therapy. Logistic regression identified B cells with bound PLTs as a predictor for distinguishing lcSSc patients. CONCLUSIONS:B cells with bound PLTs play a significant role in SSc by modulating B cell function and contributing to disease pathogenesis. Their association with clinical parameters suggests their potential as biomarkers for disease severity and subtype classification in SSc.

BACKGROUND:Idiopathic inflammatory myopathies (IIM) are a diverse group of muscle diseases often complicated by interstitial lung disease (ILD), which significantly impacts morbidity and mortality. Krebs von den Lungen-6 (sKL-6) has been proposed as a biomarker for ILD severity. Nailfold videocapillaroscopy (NVC) detects microvascular changes, but its diagnostic and prognostic value in IIM remains unclear. OBJECTIVE:This study aimed to assess the relationship between NVC abnormalities, sKL-6 levels and pulmonary outcomes in IIM patients. METHODS:A retrospective analysis was conducted in IIM patients from a reference centre, comparing those with and without ILD. Data included epidemiological, clinical and immunological features, pulmonary function tests, sKL-6 levels and NVC findings. Statistical analyses included Spearman's rank correlation coefficient to assess the relationships between sKL-6 levels, pulmonary function tests and NVC parameters. Multiple logistic regression modelling to identify to identify predictors of IIM-ILD. RESULTS:Among 95 patients (34% male, median age 55.3 ± 24 years, disease duration 6.8 ± 7 years), ILD was associated with avascular zones (P = 0.004), capillary loss (P = 0.04) and microhaemorrhages (P = 0.04). Negative correlations were observed between capillary loss and enlarged capillaries with forced vital capacity (%FVC) (rs = -0.46, P = 0.001; rs = -0.57, P < 0.0001) and diffusing capacity of the lungs for carbon monoxide (%DLCO) (rs = -0.32, P = 0.04; rs = -0.23, P = 0.03). sKL-6 levels correlated positively with ILD (rs = 0.77, P = 0.0004), microhaemorrhages (rs = 0.21, P = 0.04) and avascular areas (rs = 0.64, P = 0.03), and negatively with %FVC (rs = -0.47, P = 0.001) and %DLCO (rs = -0.59, P = 0.005). Predictors of ILD included male sex, respiratory symptoms, %FVC, %DLCO, sKL-6, anti-Jo1 positivity and NVC abnormalities. CONCLUSIONS:NVC findings, sKL-6 levels, and autoantibodies are valuable in identifying and monitoring ILD in IIM, highlighting their role in early diagnosis and management.

Objective: To evaluate the real-world safety and efficacy of macitentan (MACI) in patients with systemic autoimmune rheumatic diseases (SARDs) and refractory digital ulcers (DUs). Methods: We conducted a retrospective observational study of 42 patients treated with MACI (10 mg/day) on a compassionate-use basis across Spanish reference hospitals. Given the cohort’s heterogeneity, a two-step analysis was performed: a global assessment of all patients, followed by a subgroup analysis restricted to those with systemic sclerosis (SSc) or fulfilling very early SSc (VEDOSS) criteria to explore predictors of response. Efficacy was defined as complete healing, partial response, or a lack of response based on physician assessment. Safety was evaluated through analysis of adverse events. Results: In the global cohort, MACI demonstrated a high rate of complete ulcer healing (82.9%) at the 3-month follow-up, with a significant reduction in median ulcer count (p < 0.001). Subgroup analysis within the SSc/VEDOSS cohort (n = 36) revealed that the presence of gastrointestinal involvement (GI) and a higher baseline DUs were significant predictors of a poorer therapeutic response (p = 0.022 and p = 0.028). The drug was well-tolerated; adverse events were infrequent and rarely led to treatment discontinuation. Conclusions: In this real-world refractory population, MACI was associated with rapid DU healing and a favorable safety profile. GI and higher ulcer burden predicted diminished treatment response in SSc patients. These results support the use of MACI as a valuable therapeutic option for severe digital vasculopathy in SARDs, although further prospective studies are warranted to confirm these observations.

Purpose of reviewThe intersection of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and interstitial lung disease (ILD) represents a complex and increasingly recognized clinical challenge. This review aims to summarize current understanding, highlight diagnostic and therapeutic approaches, and identify key gaps in the literature regarding ANCA-associated ILD.Recent findingsANCA positivity-particularly MPO-ANCA- is increasingly identified in patients with fibrotic ILD, even in the absence of systemic vasculitis. This overlap raises questions about disease classification and management, especially as radiologic patterns such as usual interstitial pneumonia (UIP) appear to predict prognosis. Immunosuppressive therapy remains the mainstay of treatment, though its role varies depending on the presence of systemic features and lung fibrosis. Emerging biomarkers, and the potential role of antifibrotic agents offer promising avenues for improved monitoring and therapy.SummaryANCA-ILD represents a heterogeneous and underexplored disease spectrum that challenges existing classification systems. A multidisciplinary approach is critical, and prospective studies are urgently needed to redefine diagnostic criteria and guide treatment strategies in order to improve clinical outcomes.

Objectives The 2022 European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines for pulmonary arterial hypertension (PAH) recommend risk stratification to optimize management. However, the performance of generic PAH risk stratification tools in patients with SSc-associated PAH remains unclear. Our objective was to identify the most accurate approach for risk stratification at SSc-PAH diagnosis.Methods In this multicentre, international cohort study from the European Scleroderma Trials and Research (EUSTAR) group database, we screened 11 risk stratification tools upon SSc-PAH diagnosis. We compared the performance of the three top-ranked tools to predict mortality with the ESC/ERS three-strata model, the currently recommended tool for baseline risk assessment. We also assessed the impact of incorporating SSc-specific characteristics into the tools. Kaplan-Meier analyses and Cox regression with area under the ROC curve (AUC) were conducted.Results The ESC/ERS three-strata model had a lower ability to predict mortality than the ESC/ERS four-strata model, 'SPAHR updated' and 'REVEAL Lite 2'. The ESC/ERS four-strata model divided 'intermediate-risk' patients into two groups with significantly different long-term survival rates and is the easiest applicable tool. Incorporating SSc-specific characteristics did not significantly improve the predictive ability of any model, but a low diffusing capacity of the lung for carbon monoxide (DLCO) was an independent predictor of mortality.Conclusion Considering its ability to predict mortality, risk segregation capabilities and clinical applicability, this study provides a rationale for using the simplified ESC/ERS four-strata model at SSc-PAH diagnosis as an alternative to the comprehensive ESC/ERS three-strata model. We propose considering DLCO as an individual prognostic marker in SSc-PAH.

OBJECTIVE:ACA-positive interstitial lung disease (ILD) in SSc is traditionally considered less aggressive than anti-topo I antibody (ATA)-positive ILD. However, its clinical profile and prognosis remain poorly defined. We aimed to characterize ACA-associated SSc-ILD and compare it with other serological subsets. METHODS:Multicentre cross-sectional observational study including 76 ACA-positive SSc-ILD patients, compared with ATA-positive (n = 54) and ACA/ATA-negative (n = 147) groups. RESULTS:ACA-positive patients developed ILD earlier than ATA-positive and ACA/ATA-negative individuals (2.5 vs 5.6 and 3.5 years; P = 0.389). Compared with the other groups, they had higher pFVC (96.3% vs 83.5% and 86.9%; P = 0.013), lower pFEV1/pFVC ratio (91.6% vs 99.2% and 98.8%; P = 0.004) and better functional capacity, with fewer NYHA class III-IV patients (14.5% vs 42.6% and 32%; P = 0.017). They also showed lower pKCO (71.7% vs 85.1% and 77.4%; P = 0.008) and higher pFVC/pDLCO ratio (1.8 vs 1.4 and 1.5; P = 0.016), suggesting indolent microvascular damage and increased pulmonary vascular resistance. Differences in pDLCO were not significant (60.2% vs 60.9% and 65.7%; P = 0.769). ILD worsening (ATS criteria) occurred in 14.5% of ACA-positive patients. No significant differences were found in antifibrotic indication or advanced interventions. However, 2.6% underwent lung transplantation (0% ATA-positive, 1.4% ACA/ATA-negative) and 2.6% received autologous haematopoietic stem cell transplantation (0% and 3.4%, respectively). Overall survival analysis revealed no significant differences across the three groups (P = 0.164), although ACA/ATA-negative patients showed better survival than ACA-positive patients (P = 0.041; HR 0.498, P = 0.045). CONCLUSION:ACA-positive SSc-ILD does not seem to have a more favourable long-term prognosis compared with other serological subsets.

Interstitial lung disease (ILD) is a common and potentially devastating complication of systemic sclerosis (SSc), a chronic autoimmune disorder characterized by fibrosis and vascular abnormalities. The association between SSc and ILD underscores the intricate interplay between immune dysregulation, vasculopathy, and tissue fibrosis. This review provides a comprehensive overview of the immunological, clinical, and radiological features of ILD in the context of SSc. It highlights the diverse spectrum of ILD patterns observed in SSc patients, ranging from non-specific interstitial pneumonia to usual interstitial pneumonia. The intricate pathogenic mechanisms linking SSc and ILD involve aberrant immune responses, endothelial dysfunction, profibrotic cytokine signaling, and genetic factors. Immunological alterations, diagnostic challenges, and prognostic implications are discussed, underscoring the need for multidisciplinary management strategies. By elucidating the complex relationship between SSc and ILD, this review aims to contribute to a deeper understanding of the underlying mechanisms and facilitate the development of interdisciplinary interventions for improved patient outcomes.

Background: Primary Sjögren’s Syndrome (pSS) is a systemic autoimmune disease characterized by salivary gland involvement. Some patients may develop systemic extra glandular manifestations that can determine the prognosis of the disease. The influence of serological and immunological biomarkers on the clinical expression of the disease is still not fully known, nor is their role as prognostic factors of the disease. Objectives: The aim of the study was to assess the prevalence of extraglandular involvement in pSS, as well as to determine the relationship between immunological and serological biomarkers, disease activity, and extraglandular manifestations in patients with pSS. Methods: A cohort of patients with pSS who met the ACR/EULAR classification criteria for pSS in 2016 followed up in our Systemic Autoimmune Diseases Unit between 2000 and 2022 was carried out. The sociodemographic, clinical, serological and immunological data and the Disease activity measures calculated with the ESSDAI index (EULAR Sjögren’s Syndrome disease activity index) were collected. For the comparison of qualitative and/or quantitative variables, Fisher’s exact test or the T-test was performed when necessary. Results: 175 patients with pSS were included (85% were women), with a mean age at diagnosis of 58.8±12.2 years and a disease evolution time of 7.6±5.4 years. 62 patients (35%) had extraglandular manifestations. Anti-Ro60 positivity was found in 68%, Anti-Ro52 in 35.3% and anti-Ro60 and anti-La in 47.4% of patients. Associations between serological markers and systemic manifestations in patients with pSS is summarized in Graph 1 and Table 1. A higher risk of renal involvement was found in anti-Ro60, meanwhile a lung involvement, hypocomplementemia and higher levels of rheumatoid factor and hypergammaglobulinemia were associated with anti-Ro52 positivity. Constitutional symptoms, hematological involvement, lymphadenopathy, higher erythrocyte sedimentation rate and ESSDAI score were associated with both anti-Ro and anti-La positivity. Cutaneous involvement was specifically associated with anti-Ro52, C3 levels, IgG and IgM levels. Articular involvement was associated with higher rheumatoid factor levels. Renal involvement was associated with C3 levels, rheumatoid factor, ESR levels, IgG levels and anti-Ro60. Lung involvement was associated with ESR levels and C-reactive protein, IgG, C3 levels and anti-Ro52 positivity. CNS involvement was associated with C3 levels, C-reactive protein and beta2microglobulin and hematological involvement with C3, rheumatoid factor, beta2microglobulin and IgG levels. Conclusion: Our results have demonstrated the role of immunological and serological biomarkers in the clinical expression of pSS and as prognostic factors for disease progression, as well as their applicability in clinical practice. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.Graph 1Systemic manifestations accordingly to autoantibodies Table 1Associations between serological markers and systemic manifestations in patients with pSSC3C4RFESRCRPbeta2microglobulinIgGIgMAnti-Ro60Anti-LaAnti-Ro52Glandularp= 0.40p=0.91p= 0.06p=0.26p=0.69p=0.94p=0.55p= 0.92p=0.002p=0.04p=0.06Cutaneousp=0.003p=0.44p= 0.12p= 0.946p=0.85p=0.59p=0.03p=0.02p=0.23p=0.12p=0.04Articularp 0.23p 0.87p=0.003p=0.12p=0.23p=0.15p=0.06p=0.15p=0.34p=0.87p=0.32Renalp=0.04p=0.32p=0.007p=0.33p=0.53p=0.12p=0.033p=0.65p=0.40p=0.22p=0.45Lungp=0.03p=0.44p=0.45p=0.04p=0.001p=0.13p=0.02p=0.42p=0.26p=0.75p=0.02CNSp=0.04p=0.45p=0.62p=0.24p=0.12p=0.01p=0.39p=36p=0.52p=0.32p=0.14PNSP=0.62P=0.44P=0.64P=0.39P=0.38P=0.77P=0.55P=0.38P=0.42P=0.13P=0.92Hematologicalp=0.03p=0.179p=0.02p=0.01p=0.98p=0.001p=0.03p=0.22p=0.45p=0.45p=0.33Constitutionalp=0.003p=0.54p=0.21p=0.02p=0.94p=0.89p=0.21p=0.92p=0.42p=0.71p=0.23Lymphadenopathyp=0.19p=0.54p=0.02p=0.17p=0.8p=0.001p=0.49p=0.37p=0.78p=0.13p=0.35

Introduction: There are few studies investigating the clinical profile of older patients with interstitial lung disease (ILD), so this study investigated the characteristics of the older population diagnosed with ILD.Material and Methods: Retrospective study in a population of new referrals at an ILD clinic from January 2013 to September 2017. Patients over 64 years were selected. Data collection included diseases variables, diagnostic procedures and comorbidities. Gender-age-physiology (GAP) stage, composite physiologic index (CPI) and Charlson Index was calculated. Statistical analysis was performed to investigate risk factors associated with survival.Results: A total of 232 patients were included in this study. Mean age was 76.3 years (SD 6.5). As per protocol, 69.3% completed the initial assessment but this was lower in the elderly group (61.5%). The most frequent diagnosis was Unclassifiable ILD (24.1%), followed by ILD associated with connective tissue disease (21.6%), IPF (12.1%) and Hypersensitivity Pneumonitis (10.3%). During follow-up (36,7 months (SD 28.6)) a significant proportion of patients died (55 cases, 23.7% of the cohort), especially in the late older group (30.4%). Kaplan-Meier curves showed that those over 75 years have a worse survival even when adjusted by covariables (p< 0,001). CPI was the only score with statistical significance in a multivariate analysis (HR 1.06. p 0.006).Conclusions: Older adults with ILD featured a distinct clinical profile. Our findings highlight the need to develop non-invasive biomarkers and specific scores adapted to this age-group.

Background: The diagnosis of Immunoglobulin IgG4-related disease (IgG4-RD) lacks a definitive gold standard; however, the prevailing diagnostic criteria to date include those proposed by Umehara1 and Okazaki2. Umehara delineates diagnostic categories as definitive, probable, or possible, while Okazaki establishes the presence or absence of the disease. In 2019, ACR and EULAR3 introduced novel classification criteria necessitating a sequential application of exclusion and inclusion criteria, followed by a point count. IgG4-RD is classified if the score surpasses 20 points. Objectives: To assess the sensitivity and specificity of Okazaki, Umehara, and ACR/EULAR 2019 classification criteria for IgG4-RD in a patient cohort, and to compare them with the definitive diagnosis based on medical criteria. Methods: A retrospective study conducted at a national tertiary university center. Eligible patients were those with elevated serum IgG4 in any analytical determination, reviewing a total of 719 medical records between January 2000 and December 2023. Of these, inclusion criteria were patients with a high clinical suspicion of IgG4-RD due to compatible organ involvement or elevated IgG4. Demographic, clinical, serological, histological data, as well as variables related to classification criteria, were collected. The medical criterion, based on the criteria outlined in Figure 1, served as the reference for a definitive diagnosis. Sensitivity, specificity, positive and negative predictive values, as well as the ROC curve, were calculated. Results: A total of 39 patients with a high suspicion of IgG4-RD were included. Clinical characteristics are detailed in Figure 2. Of the 39 suspected patients, 26 (66.6%) met the definitive diagnosis according to medical criteria. Of the 26 IgG4-RD patients, 24 (92.3%) met Umehara’s criteria; 16 (66.66%) possible, 2 (8.33%) probable, 6 (25%) definitive. Seventeen (65.4%) met Okazaki’s criteria, and 18 (69.2%) met the ACR/EULAR 2019 criteria.The sensitivity of Umehara’s criteria was 69.2% if the disease was categorized as probable or definite (NPV 61.9%, PPV 100% and accuracy 79.5%). Sensitivity for Okazaki’s criteria was 65.4% (NPV 59.1%, PPV 100%, and accuracy 76.9%), and 69.2% for the new ACR/EULAR 2019 criteria (NPV 61.9%, PPV 100%, and accuracy 79.5%). For all three criteria, the specificity was 100%.The area under the curve was 0.962, 0.827, and 0.901 for Umehara, Okazaki, and ACR/EULAR 2019 criteria, respectively (p <0.000). Approximately 8% of patients were not classified by any of the three criteria but were accurately classified by the medical criteria. Conclusion: Sensitivity and the area under the curve were superior for Umehara and ACR/EULAR 2019 criteria. Eight percent of patients were not classified by any criteria, underscoring the significance of considering medical criteria. REFERENCES: [1] Umehara, Okazaki, Masaki, Kawano, Yamamoto, Saeki et. al. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Mod Rheumatol. 2012 Feb;22(1):1-14.[2] Okazaki, Umehara. Are Classification Criteria for IgG4-RD Now Possible? The Concept of IgG4-Related Disease and Proposal of Comprehensive Diagnostic Criteria in Japan. Int J Rheumatol. 2012; 2012: 357071.[3] Wallace, Naden, Chari, Choi. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease. Arthritis Rheumatol. 2020 Jan;72(1):7-19. Acknowledgements: NIL. Disclosure of Interests: None declared.Figure 1Criteria for Classifying Patients with High Suspicion of IgG4 and Medical Classification Criteria. Figure 2Baseline clinical characteristics

Background: Interstitial lung disease (ILD) stands as the primary cause of mortality in patients with Systemic Sclerosis (SSc). Despite the identification of several risk factors to develop ILD in SSc, limited research has been directed towards understanding their impact on the progression of established SSc-ILD. Objectives: This study aims to evaluate the clinical characteristics of SSc patients with ILD and to compare features between those experiencing progressive lung function decline and those without such progression. Methods: We conducted a retrospective study on a cohort of 415 SSc patients. Inclusion criteria required the confirmation of ILD by HRCT. Demographic, clinical, analytical and pulmonary function tests (PFT's) parameters before and after ILD onset were collected. Statistical significance was set at p-values<0.05. Results: 64 patients with SSc-ILD were included, most of them females (93.8%) with a mean age at diagnosis of 60.5 years. Limited SSc was observed in 59.4%, and the predominant specific autoantibody was the anti-topoisomerase (28.1%). Table 1 summarizes the patient's characteristics. Follow-up revealed a significant decline in FVC in all patients since SSc onset (2.80±0.7 vs 2.16±0.76, p=0.000) and after ILD detection (2.37±0.69 vs 2.16±0.76, p=0.000). Male sex was associated with worse %FVC at SSc-ILD onset, persisting throughout follow-up and leading to poor lung function outcomes. However, no significant differences were found in FVC decline based on clinical SSc subset (limited vs. diffuse) or SSc autoantibodies (ATA vs. ACA) after ILD onset. Smoking history, digital ulcers, and pulmonary hypertension were associated with poor lung function outcomes. No significant differences were observed in other clinical features such as myositis, arthritis, gastrointestinal involvement, renal crisis, or cancer. Rheumatoid factor (RF) positivity was associated with poorer pulmonary function after ILD diagnosis (p=0.034). The presence of a UIP pattern did not correlate with worse lung function at the onset of ILD or at follow-up, when compared to non-UIP patterns. Among the twenty-four patients who received ILD treatment, both %FVC and ml-FVC outcomes worsened, with no significant differences noted in DLCO. Conclusion: Worse lung function outcomes after SSc-ILD onset were associated to male sex, smoking history, digital ulcers, pulmonary hypertension, and RF positivity. Notably, in contrast to patients at risk of developing SSc-ILD, no significant differences were observed based on SSc subset or SSc autoantibodies in patients with established ILD. Early volume decline was observed during follow-up, even before ILD onset, in all patients within our cohort. We did not find that treatment prevents pulmonary function decline. It could be explained by the inclusion of patients with unfavorable prognosis factors and the retrospective nature of the analysis. Prospective, multicentric studies to comprehensively assess risk factors for poor prognosis and the progression SSc-ILD patients are needed. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.

OBJECTIVE:To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD). METHODS:Multicentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants. RESULTS:Twenty-eight patients were analyzed. Examining the entire study population, before treatment with RTX the mean decline in %pFVC and %pDLCO from the ASS-ILD diagnosis to the initiation of RTX treatment (T0) was -6.44% and -14.85%, respectively. After six months of treatment, RTX reversed the decline in pulmonary function test (PFT) parameters: ∆%pFVC +6.29% (95% CI: -10.07 to 2.51; p=0.002 compared to T0) and ∆%pDLCO +6.15% (95% CI: -10.86 to -1.43; p=0.013). Twenty-four patients completed one year of therapy and 22 two years, maintaining the response in PFT: ∆%pFVC: +9.93% (95% CI: -15.61 to -4.25; p=0.002) and ∆%pDLCO: +7.66% (95% CI: -11.67 to -3.65; p<0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 18% of cases. In 33% of patients who required oxygen therapy at the start of treatment, it could be discontinued. The frequency of adverse events reached 28.5% of cases. CONCLUSION:Based on our results, RTX appears to be effective as rescue therapy in most patients with recurrent or progressive ASS-ILD unresponsive to conventional treatment. The use of RTX was well tolerated in the majority of patients.

BackgroundThe anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) reported in systemic sclerosis (SSc). Especially due to low prevalence, the clinical relevance of NOR90 in SSc remains uncertain.ObjectivesTo analyze the clinical associations of NOR90 in patients with SSc in a multicentric cohort.MethodsPost-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) database, with additional information on NOR90.Further, we performed a systematic literature search, using the terms “systemic sclerosis” and “NOR90” across three databases: Medline via PubMed, Scopus, and Thomson Reuters’ Web of Science Core Collection, from inception to November 1st, 2023.ResultsOverall, 1318 patients with SSc were included (mean age 58.3 ± 13.7 years, 81.3 % female), of whom 44 (3.3 %) were positive for NOR90. Of these, 32 were also positive for one of the SSc-criteria antibodies: 9/44 (20.5 %) for anti-topoisomerase I, 18/42 (42.9 %) for anti-centromere, and 5/40 (12.5 %) for anti-RNA polymerase III. NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal (GI) symptoms compared to NOR90-negative patients. In multivariable analysis, NOR90 remained significantly associated with lower mRSS and less frequent GI symptoms.The literature search identified 17 articles, including a total number of 87 NOR90-positive out of 3357 SSc patients, corresponding to an overall prevalence of 2.6 %.ConclusionTo our best knowledge, this is the largest SSc cohort tested for NOR90 to date, confirming the NOR90 prevalence in SSc patients is around 3 %.

Background: Juvenile Idiopathic Arthritis (JIA) represents the most prevalent inflammatory rheumatic condition in childhood. Its heterogeneous nature presents challenges in identifying feasible biomarkers for effective disease monitoring. Serum calprotectin (sCal) has emerged as a potentially valuable biomarker for precisely assessing inflammatory activity in JIA. Despite various commercially available methods for sCal determination, their usage remains limited and lacks validation. Objectives: To assess the diagnostic accuracy, define an optimal threshold, and evaluate the association between disease activity status in patients with JIA and serum calprotectin measurements obtained through chemiluminescence (CLIA) and solid-phase enzyme immunoassay (EIA) techniques within a real-world clinical setting. Methods: Serum samples from 25 pediatric patients with JIA were analyzed. sCal levels were determined by CLIA and EIA methodologies. Disease activity data was collected through JADAS-27 and the Anink ACR-modified criteria (1). We conducted a comparative analysis of results obtained through CLIA and EIA techniques. Additionally, we assessed the association between distinct biomarkers and disease activity. Results: The tests demonstrated robust performance of sCal. The ideal cut-off value for sCal in identifying disease activity, as determined by ROC analysis related to JADAS-27, was 2.3 µg/mL for both CLIA and EIA techniques. Remarkably, this value aligned with the threshold routinely utilized in our center's daily clinical practice. When evaluating disease activity based on Anink's criteria, the identified optimal thresholds were 2.0 µg/mL for sCal CLIA and 2.9 µg/mL for sCal EIA. Notably, the sCal CLIA identified threshold (2.0 µg/mL) coincided with the one recommended by its commercial kit. In contrast, the thresholds proposed for CRP and ESR (3.1 mg/L and 10 mm/h, respectively), according to both JADAS-27 and Anink, were lower than the values routinely employed in daily clinical practice (5 mg/L for CRP and 20 mm/h for ESR). A good correlation was observed between sCal levels obtained by CLIA and EIA Kendall's tau-b 0.71, p<0.001). The sensitivity of sCal outperformed the conventional inflammatory biomarkers CRP and ESR, exhibiting superior accuracy in distinguishing patients with active disease. In our cohort, a notable case involved an active patient experiencing concurrent arthritis and uveitis during data collection, exhibiting a significant discrepancy in biomarker measurements showing elevated sCal levels (≥2.3µg/ml) but without a corresponding increase in CRP or ESR. However, sCal showed reduced specificity compared to CRP and ESR, resulting in the conventional biomarkers proving more effective in identifying patients in a state of remission. Conclusion: Serum calprotectin, determined through CLIA and EIA, emerges as a valuable biomarker for monitoring disease activity in patients with JIA. It exhibits good sensitivity for identifying active patients at its cutoff point of 2.3 µg/mL, especially through EIA. The results suggest sCal is superior for identifying activity, while CRP and ESR excel in distinguishing remission. The combined use of various serum biomarkers could enhance the precision of disease activity assessment in JIA. REFERENCES: [1] Anink J, Van Suijlekom-Smit LW, Otten MH, Prince FH, van Rossum MA, Dolman KM, et al. MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis. Arthritis research & therapy. 2015;17(1):200 Acknowledgements: NIL. Disclosure of Interests: None declared.