Search Results (1,239)

Objective: Chronic lung diseases (CLDs), for example, interstitial lung disease, manifest as an extra-articular complication of rheumatoid arthritis (RA). The contribution of anti-bactericidal permeability-increasing protein antibodies (BPI Abs) in lung involvement in RA or primary Sjögren’s syndrome has been reported. Studies related to anti-BPI Abs in RA with CLD are infrequent. Here, the involvement of anti-BPI Abs with RA and CLD complications was evaluated. Methods: Enzyme-linked immunosorbent assays were used to measure anti-BPI Abs in RA sera. Results: Higher anti-BPI Ab amounts were present in the RA with usual interstitial pneumonia (UIP) than without CLD (mean ± standard deviation, 10.4 ± 23.5 [ng/mL] vs. 1.3 ± 3.8, p = 0.0020). Area under the curve values of receiver operating characteristic curves for anti-BPI Ab and Krebs von den lungen-6 were alike between RA with UIP and without CLD (0.8616, 95% CI 0.8184–0.9048; 0.8716, 95% CI 0.8151–0.9282, p = 0.5933, respectively). A relationship between anti-BPI Ab and anti-carbamylated protein Ab levels was observed in RA patients (rho 0.3508, p = 1.47 × 10⁻¹⁴). Conclusions: Anti-BPI Abs were related to UIP in RA patients and might be biomarkers for UIP. These findings predict anti-BPI Abs involvement in UIP pathogenesis in RA. Full article

Tick-borne encephalitis (TBE) is a neuroinvasive flavivirus infection with a wide spectrum of clinical manifestations whose molecular mechanisms remain insufficiently characterized. MiRNAs regulate pro-inflammatory cytokine production; therefore, changes in their profiles across different forms of TBE may determine the nature of the cytokine response. The aim of this work was to identify the specific features of the circulating miRNA and cytokine profiles in different clinical forms of TBE, as well as to analyze the correlations between them. The study included patients with febrile, meningeal, and encephalitic forms of TBE, patients with inflammatory rheumatic diseases (IRD), and healthy donors. Plasma concentrations of eight miRNAs (miR-25-3p, miR-29a-3p, miR-92a-3p, miR-146a-5p, miR-146b-5p, miR-181a-5p, miR-486-3p, and miR-766-3p) were measured by stem-loop real-time RT-PCR. Cytokine concentrations (IL-1β, IL-2, IL-8, IL-18, TNF-α) were measured by ELISA. Kendall’s rank correlation test was used for the correlation analysis. In all forms of TBE, a distinct circulating miRNA signature emerges (↑ miR-25-3p, miR-146b-5p, ↑ miR-766-3p, and ↓ miR-29a-3p), which is associated with an acute antiviral response and is not specific to chronic autoimmune inflammation. Several miRNAs (miR-29a-3p, miR-92a-3p, miR-146b-5p, and miR-486-3p) showed opposite changes in TBE and IRD, pointing to fundamentally different mechanisms of immune regulation in acute neuroinfection and systemic autoimmune pathology. Several statistical associations between circulating miRNA and pro-inflammatory cytokine levels were identified. TNF-α levels positively correlated with miR-146b-5p and negatively with miR-25-3p, while IL-2 positively correlated with miR-25-3p. In the encephalitic form of TBE, IL-1β positively correlated with miR-146b-5p and miR-92a-3p. The present study is of a pilot nature. The miRNA and cytokine patterns identified here were based on a small sample size and should therefore be regarded as preliminary. Once confirmed, these signatures may provide a basis for the differential diagnosis of TBE and the development of prognostic biomarkers of disease severity. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events (irAEs), including rheumatic manifestations affecting 5–10% of treated patients. Managing rheumatic irAEs is challenging, as the use of glucocorticoids (GCs) or disease-modifying antirheumatic drugs (DMARDs) raises concerns about potentially impairing ICI antitumour efficacy. The oncological safety of DMARDs used specifically for rheumatic irAE management remains poorly characterised. Our objective was to evaluate the oncological safety profile of various rheumatic irAE treatment strategies. Methods: This single-centre retrospective observational study included 55 patients out of 104 who underwent rheumatological evaluation between July 2016 and October 2022. Patients were categorised into three groups: symptomatic treatment alone (analgesics/NSAIDs, n = 11), systemic glucocorticoids (GCs) only (n = 27), and conventional synthetic or biological disease-modifying antirheumatic drugs (csDMARDs and/or bDMARDs, n = 17). Overall survival (OS) and progression-free survival (PFS) were compared using a Kaplan–Meier analysis. Results: The three most frequent rheumatic irAE patterns were undifferentiated arthritis (n = 20), rheumatoid arthritis-like presentations (n = 14), and polymyalgia rheumatica (n = 11). Patients in the DMARD group had more severe irAEs (CTCAE grade ≥3: 30% vs. 15%, p < 0.01) and a higher baseline CRP (27.5 vs. 17.4 mg/L, p < 0.05), reflecting greater disease burden at treatment initiation. No significant difference was observed between groups for OS (p = 0.22) or PFS (p = 0.31) over a median follow-up of 34 months. Conclusions: No detrimental oncological safety signal was identified across rheumatic irAE treatment strategies, including GCs combined with csDMARDs or bDMARDs. These results support the cautious use of DMARDs as GC-sparing agents when clinically indicated, consistent with current EULAR and ESMO guidelines, and underline the need for prospective trials to optimise immunosuppressive management in ICI-treated patients. Full article

Background and Objectives: The clinical differentiation of peripheral involvement within the spondyloarthritis (SpA) spectrum remains a significant challenge. Identifying patients at the stage of psoriasis without clinical arthritis (PsO), before the onset of overt arthritis, is crucial for early disease management. MicroRNAs (miRNAs) have emerged as potential epigenetic regulators in inflammatory rheumatic diseases. This study aimed to identify circulating miRNA profiles that serve as discriminative biomarkers between PsO and peripheral SpA (p-SpA). Materials and Methods: This exploratory study was conducted in two phases. In the preliminary discovery phase, plasma miRNA expression was analyzed using high-throughput microarrays in patients with p-SpA (modeled by peripheral psoriatic arthritis, n = 6), PsO (psoriasis without clinical arthritis, n = 3), and osteoarthritis (n = 3). In the validation phase, candidate miRNAs were verified using TaqMan-based qPCR in an independent cohort (n = 30) of various SpA phenotypes, categorized into those with peripheral arthritis (SpA-A) and those without (SpA-N). Results: The preliminary discovery phase identified altered levels of hsa-miR-140-5p, hsa-miR-192-5p, and hsa-miR-146a-5p among the groups; however, due to the small sample size, these initial findings required strict downstream verification. Functional enrichment analysis revealed that these candidate miRNAs primarily targeted the NF-κB signaling pathway (hsa04064) and Toll-like receptor (TLR) signaling pathway (hsa04620). The validation cohort confirmed that these three miRNAs could reliably differentiate SpA-A from SpA-N patients. Furthermore, bioinformatic mapping predicted that downstream targets, including TRAF6, IRAK1, and CXCL2, may be associated with these clinical phenotypes, serving as hypothesis-generating observations for future studies. Conclusions: Our findings suggest that specific plasma miRNA profiles are associated with the inflammatory pathways driving peripheral involvement in the SpA spectrum. These miRNAs represent potential biomarkers associated with peripheral arthritis in the SpA spectrum. While they offer new molecular insights into disease pathogenesis, their predictive value for identifying PsO patients at risk of developing overt arthritis requires confirmation in future longitudinal studies. Full article

Systemic sclerosis (SSc) is a severe autoimmune rheumatic disease with high mortality. Epigenetic factors, particularly micro-RNAs (miRNAs), may contribute to its pathogenesis by regulating gene expression. In this cross-sectional study, we assessed altered miRNA–mRNA regulatory networks in SSc and associated them with disease-related biological processes. We analyzed the miRNA profiles and differentially expressed genes (DEGs) of peripheral blood mononuclear cells (PBMCs) from 52 SSc patients (42 women and 10 men; mean age: 59.1 years) and 24 age- and gender-matched healthy controls. Total RNA was isolated and subjected to high-throughput next-generation sequencing for both miRNA and mRNA profiling. We identified 58 differentially expressed miRNAs (DEMs), 33 upregulated and 25 downregulated in SSc. In parallel, 6610 DEGs were detected (Mann–Whitney U-test, p < 0.05); 31 remained upregulated and nine downregulated after false discovery rate (FDR) correction. Integration of miRNA and mRNA data revealed 180 validated inverse miRNA–mRNA interactions. Notably, 22 of 31 upregulated DEGs corresponded to targets of downregulated miRNAs, indicating coordinated derepression. Functional enrichment analyses highlighted pathways related to extracellular matrix (ECM) remodeling, immune responses, fibrosis, and transcriptional regulation. Our findings suggest that altered miRNA expression contributes to widespread transcriptional dysregulation in SSc, promoting pro-fibrotic and immune-activated molecular pathways through coordinated miRNA–mRNA interactions. Full article

Background and Objectives: Rheumatic diseases confer excess cardiovascular risk, yet prognosis after acute coronary syndrome (ACS) in contemporary angiography-treated care remains incompletely characterized, particularly when psychiatric multimorbidity is considered. We evaluated whether documented rheumatic disease was associated with psychiatric comorbidity and post-discharge mortality after ACS. Materials and Methods: We retrospectively analyzed a predefined two-center registry extract of 2950 consecutive patients who underwent coronary angiography for ACS. Documented rheumatic disease was identified from diagnoses recorded in admission history, prior medical records, or discharge documentation and was not re-adjudicated. The primary outcome was post-discharge all-cause mortality. Results: Documented rheumatic disease was present in 106 patients (3.6%). Compared with patients without documented rheumatic disease, exposed patients were older, more often women, more often hypertensive, and more likely to have a documented psychiatric disorder (25.5% vs. 14.1%). Short-term mortality was similar, whereas crude overall long-term mortality was higher (27.4% vs. 19.3%). Among hospital survivors with usable follow-up, post-discharge survival was worse (log-rank p = 0.013). Documented rheumatic disease was associated with higher post-discharge mortality in unadjusted analysis (hazard ratio 1.66, 95% confidence interval 1.11–2.48) and in a prespecified parsimonious model (adjusted hazard ratio 1.56, 95% confidence interval 1.04–2.34); the association attenuated and was no longer statistically significant in a broader exploratory model (adjusted hazard ratio 1.35, 95% confidence interval 0.87–2.07). Documented psychiatric disorder independently predicted mortality. Conclusions: In angiography-treated ACS, documented rheumatic disease was associated with greater psychiatric comorbidity and worse post-discharge survival in a small, documentation-defined, heterogeneous subgroup. Because the signal attenuated in broader exploratory adjustment and exposure ascertainment was documentation-based, the findings should be regarded as hypothesis-generating rather than disease-specific or causal. Full article

Rheumatoid arthritis (RA) is a systemic rheumatic disease. Its most prominent characteristic is synovitis, which manifests clinically as arthritis, resulting in joint damage. Interstitial lung disease (ILD) is an extraarticular manifestation of RA that hinders therapeutic goals, affects life prognosis, and can be worsened by the administration of disease-modifying antirheumatic drugs (DMARDs). Therefore, proper management of ILD, including consideration of risk factors such as the systemic disease activity of RA and autoantibodies, and early detection with high-resolution computed tomography are required at the introduction of DMARDs. Methotrexate, a class of DMARD used as the anchor drug for RA treatment, has been recognized as likely to worsen RA-ILD. However, there are currently reports suggesting that methotrexate may have beneficial effects on RA-ILD. Conversely, several studies have also shown exacerbations of ILD with the administration of biological DMARDs, which are thought of as tolerable for patients with RA-ILD. Rheumatologists should be wary of emergence or changes in the activity of ILD and arthritis during treatment of any kind with DMARDs. Further studies are warranted to clarify underlying ethnic factors, such as the possible effects of antimelanoma differentiation-associated gene 5 antibodies on RA-ILD. Full article

Background/Objectives: Systemic sclerosis (SSc) is a heterogeneous systemic autoimmune rheumatic disease characterized by immune dysregulation, vasculopathy, and fibrosis involving the skin and internal organs. Interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and cardiac involvement remain major causes of morbidity and mortality, yet prediction of disease progression and therapeutic responsiveness remains difficult. Methods: This narrative review summarizes studies of circulating blood biomarkers in SSc, with emphasis on literature published since 2020 and on Japanese multicenter longitudinal cohort studies. Disease-specific autoantibodies were intentionally excluded from the main scope, and the review focuses on soluble biomarkers measurable in peripheral blood that reflect inflammation, endothelial injury, and fibrotic remodeling. Results: Multiple cytokines, chemokines, adhesion molecules, endothelial markers, extracellular vesicle-associated molecules, and extracellular matrix (ECM)-related molecules have been associated with disease activity, organ involvement, prognosis, and therapeutic response in SSc. Clinically established biomarkers such as KL-6 and surfactant protein-D (SP-D) for SSc-associated interstitial lung disease (ILD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for pulmonary arterial hypertension (PAH), are already used as adjunctive tools in routine clinical assessment, whereas many other candidate biomarkers, including interleukin (IL)-6, CCL2, CXCL8, CXCL4, intercellular adhesion molecule-1 (ICAM-1), CCL18, periostin, endostatin, endothelin-1, extracellular vesicle signatures, and ECM turnover markers remain at varying stages of clinical validation. In particular, Japanese multicenter longitudinal studies have demonstrated the prognostic significance of circulating chemokines and adhesion molecules in early SSc and, more recently, identified biomarker-based clusters associated with distinct pulmonary trajectories. Recent multidimensional proteomic and transcriptomic approaches further support biologically based patient stratification in SSc. Conclusions: Blood biomarkers may contribute to risk stratification, prediction of organ progression, and future precision medicine in SSc. Integrated biomarker signatures may better capture the biological heterogeneity of SSc than single biomarkers alone. However, most candidate biomarkers still require external validation, assay standardization, and demonstration of incremental value over conventional clinical variables before routine clinical implementation. Full article

Background/Objectives: Primary Sjögren’s syndrome (pSS) is a chronic autoimmune rheumatic disease that clinically presents with symptoms of xerostomia and xerophthalmia, as well as a wide range of other symptoms that may affect patients’ daily functioning and life satisfaction. The main purpose of this study was to assess their health-related quality of life (HRQoL) using both general and disease-specific questionnaires. Methods: This cross-sectional observational research with prospective data collection was conducted at the Rheumatology Clinic of the University Clinical Centre of Kragujevac. Participants were divided into two groups: patients with oral manifestations (oral manifestations group) and those presenting with xerostomia only, without other oral lesions or symptoms (xerostomia-only group). A complete clinical examination of the patient’s oral cavity was performed by one doctor of dental medicine. HRQoL was evaluated using various generic and disease-specific instruments. Results: A total of 80 participants were included in the study, of whom 40 were in the oral manifestations group and 40 in the xerostomia-only group. Patients with oral manifestations had significantly higher scores across all PSS-QoL domains compared with the xerostomia-only group (p < 0.001). A statistically significant difference in the total EQ-5D result was detected between groups (0.7 (0.3) vs. 0.8 (0.1), p < 0.001). In multivariable regression analysis (R² = 0.921), the ESSPRI score (β = 0.418, p < 0.001) and the presence of oral manifestations (β = −1.155, p < 0.001) were significant independent predictors of impaired HRQoL, while disease activity showed no significant association (p = 0.895). Conclusions: Patients with primary Sjögren’s syndrome presenting with oral manifestations have poorer HRQoL compared with participants with xerostomia only. Symptom burden, including dryness, pain, fatigue, and oral manifestations, may be associated with decreased HRQoL, in contrast to disease activity. Full article

Background: Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by inflammation, vasculopathy, and fibrosis. It is associated with the highest mortality among rheumatic diseases. Very early SSc may represent a critical phase with risk of developing progressive disease. Although timely treatment may be effective in patients with progressive disease, it carries risks of adverse events, underscoring the need for early identification of individuals at risk. Biomarkers for progression in the early stage offer opportunities for timely intervention and improved long-term outcomes. Therefore, validating biomarkers that predict progression is an important research priority. In this narrative literature review, we summarize and evaluate blood circulating biomarkers associated with different progression endpoints in (very) early SSc. Methods: The literature search was conducted using PubMed. Eligible studies assessed biomarkers in very early SSc or early SSc cohorts with longitudinal follow-up and progression-related outcomes. Results: The identified studies investigated biomarkers associated with interstitial lung disease (ILD), skin progression, overall disease progression, and mortality. Anti-topoisomerase I was associated with ILD development. A high interferon score was linked to reduced lung function and mortality. KL-6 was associated with progression in early SSc-ILD. PRO-C3 and PRO-C6 showed the strongest associations with skin involvement. Finally, IgG anti-centromere antibody was associated with organ involvement and progression to definite SSc. CXCL10 and TNFRII were linked to progression and significant survival differences in the discovery and replication cohorts. However, effect sizes were often modest, and findings were inconsistent across cohorts. Substantial heterogeneity in study design, populations, endpoints, and biomarker assessment methods limited comparability. Moreover, most biomarkers demonstrated associations at the group level but lacked sufficient discriminatory power for individual risk prediction. Only a minority of studies included validation cohorts, and replication of findings was limited. Conclusions: Multiple biomarkers show promising associations with progression in very early and early SSc, but a single biomarker is unlikely to reliably predict disease progression. Full article

Background/Objectives: Ankylosing Spinal Disorders (ASDs) encompass a heterogeneous group of rheumatic diseases characterized by progressive ankylosis of the axial skeleton, including Ankylosing Spondylitis (AS), Diffuse Idiopathic Skeletal Hyperostosis (DISH), and Non-Radiographic Axial Spondyloarthritis (nr-AxSpA). Spinal ankylosis profoundly alters the biomechanical properties of the vertebral column, transforming it into a rigid long-bone equivalent and dramatically increasing fracture risk even after low-energy trauma. Once a fracture occurs, the long lever arm created by the ankylosed segments generates enormous mechanical stress at the fracture site, making surgical stabilization mandatory in the vast majority of cases. Long posterior instrumentation is the treatment of choice; however, no consensus exists regarding the optimal number of instrumented levels. The aim of this study is to clinically and radiologically evaluate long posterior instrumentation in the 3 + 3 (3 proximal and 3 caudal screws), 3 + 2 (3 proximal and 2 caudal screws), or 2 + 2 (2 proximal and 2 caudal screws) configuration for the treatment of traumatic ASD thoracolumbar vertebral fractures, in terms of implant failure, infection rate, and mortality. Methods: Between 2018 and 2023, 65 consecutive patients with ASD-related thoracolumbar vertebral fractures were treated at our institution. After applying pre-defined inclusion and exclusion criteria, 37 patients were enrolled. Patients were retrospectively divided into three groups according to the posterior arthrodesis configuration (notation indicates number of instrumented vertebral levels proximal + distal to the fracture: 3 + 3, 3 + 2, or 2 + 2). Radiological outcomes were assessed for loosening, screw cut-out, and implant breakage. Infection and mortality rates within 3 months from surgery were evaluated as secondary endpoints. Statistical analysis was performed using the Fisher exact test (significance set at p < 0.05). Results: Thirty-seven patients (28 males and 9 females; mean age 77 ± 7.3 years) were included, with a mean follow-up of 30 ± 5.3 months. Instrumentation configurations were as follows: 23 (3 + 3), 5 (3 + 2), and 9 (2 + 2). Three implant failures (8.1%) and four infections (10.8%) were recorded. Eleven patients died within 3 months of surgery. A statistically significant difference was found between instrumentation length and mechanical complications (p = 0.0468), while no significant difference was observed for infection (p = 1) or mortality rate (p = 0.137). Conclusions: In this exploratory retrospective cohort, the 3 + 3 configuration was associated with the lowest observed rate of implant failure in ASD thoracolumbar fractures, suggesting a potential mechanical advantage over shorter constructs that warrants confirmation in larger prospective studies. No significant correlation was found between instrumentation length and infection rate or early mortality. Prospective, multicentre studies with larger cohorts are warranted to establish definitive guidelines for instrumentation length in this challenging patient population. Full article

This study evaluated routinely measured serum complement C3c (C3c) and complement C4 (C4) in relation to systemic inflammation, clinical and immunological phenotypes, and patient-reported outcomes (PROs) in systemic sclerosis (SSc). Seventy SSc patients fulfilling the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria underwent same-day assessment including serum C3c, C4, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), autoantibodies, immunosuppressive therapy and PROs. Associations were analysed using Spearman correlations and linear regression. C3c correlated strongly with CRP (rho = 0.53, p < 0.001) and ESR (rho = 0.49, p < 0.001) and remained independently associated with CRP (regression coefficient β = 0.26 mg/L per mg/dL, 95% confidence interval [CI] 0.14–0.38, p < 0.001) and ESR (β = 0.32 mm/h per mg/dL, 95% CI 0.16–0.47, p < 0.001), explaining ~17% and 15% of their variance. C4 showed weaker correlations with CRP (rho = 0.37, p = 0.004) and ESR (rho = 0.29, p = 0.03). Neither C3c nor C4 correlated with IL-6, modified Rodnan skin score (mRSS), interstitial lung disease (ILD), gastrointestinal involvement, SSc subset, autoantibodies, immunosuppressive therapy or PROs. C3c and C4 levels were significantly lower in patients with secondary Sjögren’s disease (SjD) than SSc-only. Serum C3c reflects acute-phase response in SSc, paralleling CRP and ESR but not clinical phenotype or patient-perceived burden, whereas C4 provides only weaker, secondary information. Full article

Ankylosing Spondylitis (AS) is a chronic inflammatory autoimmune rheumatic disease that primarily affects the spine and sacroiliac joints. This study aimed to investigate the expression levels of immune response-related genes, including IRF7, NFKB1A, TNFAIP3, STAT1, TRIM21, TRIM22, and TRIM25, as well as the serum levels of CXCL10 and SIRPA proteins in patients with AS. In addition, the potential diagnostic performance of these molecular and serum biomarkers in distinguishing patients with AS from healthy controls was evaluated. A total of 45 patients with AS and 44 healthy controls were included in the study. Immune-related gene expression levels were analyzed using RT-PCR. In addition, serum CXCL10 and SIRPA protein levels were evaluated using ELISA. The expression levels of NFKB1A, TNFAIP3, IRF7, STAT1, and TRIM21 were significantly increased in patients with AS compared to healthy controls (p < 0.05). In contrast, no significant differences were detected in the expression levels of TRIM22 and TRIM25. In the ROC analysis, the highest diagnostic performance was obtained for NFKB1A (AUC = 0.741), TNFAIP3 (AUC = 0.720), and TRIM21 (AUC = 0.722). Serum CXCL10 and SIRPA levels were not significantly different between the groups. In AS, genes particularly associated with NF-κB and interferon signaling pathways (NFKB1A, TNFAIP3, IRF7, STAT1, and TRIM21) were found to be significantly altered, and these genes may serve as potential molecular biomarkers for AS. In contrast, the diagnostic power of serum protein biomarkers is limited. These findings indicate that the potential of these genes as biomarkers for AS pathogenesis should be further supported by advanced studies evaluating their expression levels. Full article

(1) Background: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease associated with immune dysregulation. The TYRO3, AXL, and MER (TAM) signaling pathway, comprising AXL receptor tyrosine kinase (AXL), MER tyrosine kinase (MERTK), growth arrest-specific 6 (GAS6), and Protein S, is a key regulator of immune homeostasis. This study investigated these receptor–ligand components in patients with AS. (2) Methods: A total of 45 patients with AS and 44 healthy controls were enrolled. Serum GAS6 and Protein S levels were measured by ELISA, and AXL and MERTK expression levels were analyzed by RT-qPCR. Clinical and inflammatory parameters were also evaluated. (3) Results: ESR, CRP, and IL-6 levels were significantly higher, whereas Protein S levels were significantly lower in patients with AS than in controls. No significant differences were observed in GAS6, AXL, or MERTK expression levels, although lower expression trends were detected in patients. Logistic regression analysis identified CRP, IL-6, Protein S, and AXL expression as variables independently associated with AS. ROC analysis demonstrated significant discriminatory performance for AXL expression. (4) Conclusions: Alterations in the TAM signaling pathway, particularly reduced Protein S levels and altered AXL expression, may contribute to immune dysregulation and persistent inflammation in AS. Full article

Background: Systemic autoimmune rheumatic diseases-associated interstitial lung disease (SARD-ILD) presents with varied disease courses, emphasizing the need for reliable predictors of progression. The prognostic utility of bronchoalveolar lavage (BAL) in SARD-ILD remains underexplored. The objective of this study was to evaluate the role of BAL fluid lymphocyte count in predicting disease progression in patients with SARD-ILD. Methods: This observational study included patients with SARD-ILD undergoing BAL as part of their diagnostic workup. Disease progression was defined as either Forced vital capacity (FVC) decrease >10%, two out of the following three criteria within two years: FVC decrease of 5–10%, worsening symptoms, increased fibrosis on imaging, or any of the following: escalation of treatment, Interstitial lung disease (ILD) exacerbation, lung transplantation, or disease-specific mortality. Logistic regression identified predictors of progression. Time-to-progression was assessed using Kaplan–Meier survival curves. The optimal BAL lymphocyte threshold for predicting progression was identified using the Youden Index and the Wilcoxon method. Results: We identified 89 patients, of whom 30 (33.7%) had progressive disease. Progressors had a significantly higher BAL lymphocyte count compared to non-progressors (31.6 ± 24.8% vs. 14.3 ± 16.5%, p < 0.001). BAL lymphocyte proportion was significantly and independently associated with disease progression (odds ratio, 1.05; 95% confidence interval 1.02–1.07; p < 0.01). A lymphocyte count above 9 percent was associated with a markedly increased risk of disease progression (odds ratio, 13.14; 95% confidence interval, 4.20–51.98; p < 0.01). Conclusions: BAL lymphocyte count was associated with a higher likelihood of progression in SARD-ILD. BAL assessment may help identify patients at increased risk of disease progression. However, these findings should be considered exploratory and require validation in larger prospective studies and across individual SARD-ILD subtypes. Full article