Search Results (87)

Background: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Despite the implementation of the treat-to-target (T2T) strategy and the introduction of several classes of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), a considerable proportion of patients continues to exhibit active, refractory disease. In 2021, the European Alliance of Associations for Rheumatology (EULAR) defined this condition as Difficult-to-Treat Rheumatoid Arthritis (D2T-RA). This study aimed to identify clinical, laboratory, and therapeutic factors associated with D2T-RA. Methods: A total of 344 patients with established RA were retrospectively evaluated. Among them, 164 fulfilled the 2021 EULAR criteria for D2T-RA (D2T group), while 180 did not (NO-D2T group). Clinical (age, sex, disease duration, BMI, smoking, comorbidities), laboratory (RF, ACPA, ESR, CRP), clinimetric (DAS28, CDAI, PhGA, PGA, HAQ), and therapeutic data (glucocorticoid use, methotrexate treatment and dose, monotherapy, advanced therapy exposure, number of failed advanced therapies, current DMARD regimen) were analyzed. Results: Factors significantly associated with D2T-RA included female sex, longer disease duration, higher RF and ACPA titers, elevated ESR levels, glucocorticoid therapy, and a greater number of failed advanced therapies. Although both groups achieved low disease activity or remission by DAS28 and CDAI, JAK inhibitors—particularly Filgotinib and Upadacitinib—were significantly more common in the D2T cohort and appeared associated with clinical stabilization. Conclusions: This study strengthens the understanding of the predictive profile of D2T-RA, confirming the role of disease chronicity and persistent inflammation in the development of treatment resistance. Importantly, the observed trend toward clinical stabilization achieved under JAK inhibitor therapy reinforces their potential to address unmet therapeutic needs in D2T-RA, providing a mechanistically grounded strategy for patients refractory to conventional and biologic DMARDs. Full article

Background/Objectives: Vitamin D levels tend to be lower in patients with inflammatory rheumatic diseases (IRDs), including rheumatoid arthritis (RA), but there are minimal data on vitamin D levels in rheumatology patients with inflammatory vs. non-inflammatory diagnoses. Methods: In this retrospective, observational study, we used electronic health record data from patients presenting for their first visit at a large rheumatology clinic to assess vitamin D levels and deficiency based on diagnosis, and to evaluate the association between vitamin D and inflammatory markers (including C-reactive protein [CRP]) or autoimmune markers (including rheumatoid factor [RF], anti-citrullinated peptide antibody, and anti-nuclear antibodies). Logistic regression analysis with 13 clinical variables was used to evaluate the association between vitamin D levels and IRD diagnosis, and linear regression was used to evaluate the association between vitamin D levels and CRP or RF. Results: The patient cohort included 4979 patients; 1385 (27.8%) had an IRD. Vitamin D levels were significantly lower in the IRD vs. non-inflammatory subgroup (mean [SD] of 26.6 [13.3] vs. 27.7 [14.3]; p = 0.009), but the difference was not clinically relevant given the small effect size. Vitamin D deficiency rates (<20 ng/mL) were not significantly different between the subgroups, and vitamin D was not associated with an IRD diagnosis in logistic regression analysis. In linear regression analysis, vitamin D was not associated with CRP or RF in the full patient cohort or in the subgroup with RA (n = 539). Conclusions: We conclude that vitamin D levels do not differ substantially based on IRD versus non-inflammatory diagnosis, CRP levels, or RF levels in this clinical cohort. Full article

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitis. The prevalence of RA is estimated to be 0.5–1% worldwide. Methods: This work investigated the therapeutic effects and underlying mechanisms of blue mussel (Mytilus galloprovincialis) oil (BMO) on RA in rats, using green-lipped mussel oil (GMO) and Antarctic krill oil (KO) as controls. Results: The results suggested that BMO, GMO, and KO all alleviated paw swelling in rats and reduced serum levels of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and pro-inflammatory cytokines such as TNF-$\alpha$ and IL-17. Histopathological assessment further revealed that BMO, GMO, and KO prevented synovial fibroplasia, mitigated inflammatory cell infiltration, and improved cartilage damage in ankle joints. Overall, BMO exhibited slightly superior alleviating effects compared with GMO and KO. Plasma lipidomics analysis revealed that the lipid metabolites altered by BMO showed significant correlations with RA-related indicators, particularly pro-inflammatory cytokines. Functional enrichment analysis suggested the involvement of inflammation-related pathways, particularly the NF-$\kappa$B signaling pathway. Further validation demonstrated that BMO effectively suppressed the production of inflammatory cytokines (TNF-$\alpha$, IL-17) and the expression of NF-$\kappa$B p65, JAK2, and STAT3 proteins in synovial tissue. And IL-17 production in footpad tissues is closely associated with CD3-positive T cells. Similar effects were also observed for GMO and KO. Conclusions: Collectively, BMO might ameliorate RA by inhibiting NF-$\kappa$B and JAK2/STAT3 signaling pathways. Full article

Background: Janus kinase inhibitors (JAKi) are approved for the treatment of rheumatoid arthritis (RA), aiming to achieve clinical remission. Composite scores such as Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP) are influenced by subjective factors, and JAKi may impact these dimensions beyond inflammation. Ultrasound provides a sensitive and objective assessment of synovial activity. Objective: To evaluate clinical and ultrasound-defined remission in RA patients treated with JAKi under routine care. Methods: This cross-sectional study included all consecutive patients treated with baricitinib, filgotinib, tofacitinib, or upadacitinib between 1 November 2022 and 30 April 2023. Clinical remission was defined as DAS28-CRP and ultrasound remission as absence of power Doppler (PD) signal across a standardized 32-joint evaluation. Results: We include 78 patients with established RA; 87.2% were female, with mean age of 59.5 ± 10.8 years and disease duration of 10.6 ± 8.0 years. Most were seropositive for RF and/or ACPA (74.4%), and comorbidities were highly prevalent (93.6%). Clinical remission was observed in 42.3% and ultrasound remission in 56.4%, with no statistically significant differences between JAKi groups. Among 50 patients meeting remission by either definition, 30 (60%) fulfilled both criteria, 11 (22%) had ultrasound remission only, and 9 (18%) met clinical remission without sonographic confirmation. Discordant cases were often associated with osteoarthritis, fibromyalgia, mood disorders, and elevated inflammatory markers. Conclusions: JAKi were effective in achieving remission in many RA patients. Ultrasound revealed residual synovitis despite clinial remission and, conversely, silent remission in cases not meeting DAS28-CRP criterion, reinforcing its value for accurate monitoring and personalized therapeutic decisions. No meaningful clinical or ultrasonographic differences were observed between the various JAK inhibitors, indicating comparable perfomance across agents in routine practice. Full article

Background: Seronegative rheumatoid arthritis (SNRA), defined by the absence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), represents 20–30% of rheumatoid arthritis cases. Once considered a milder phenotype, SNRA is now recognised as a heterogeneous entity in which a substantial subset of patients develops structural progression comparable to seropositive RA. The binary RF/ACPA-based definition is increasingly viewed as insufficient, as the broader anti-modified protein antibody (AMPA) family—including antibodies against carbamylated, acetylated and malondialdehyde–acetaldehyde–modified proteins—indicates that many “seronegative” patients may harbour unconventional humoral autoimmunity undetected by standard assays. Objectives: To synthesise contemporary insights into the epidemiology, immunopathology, diagnostic challenges and therapeutic management of SNRA, with emphasis on erosive versus non-erosive phenotypes and the implications of the AMPA paradigm. Methods: A comprehensive literature search of PubMed, Cochrane Library and Google Scholar identified randomised trials, observational cohorts and systematic reviews, with focus on studies published within the past decade. Results: SNRA displays partially distinct immune features, including lower formation of tertiary lymphoid structures and variable activation of innate inflammatory circuits. However, the traditional adaptive–versus–innate dichotomy is overly reductionist. Growing evidence suggests that unconventional humoral responses directed against non-classical post-translational modifications may be present in a proportion of RF/ACPA-negative patients. Additional qualitative dimensions—such as IgA isotypes and fine-specificity profiles—represent further heterogeneity with potential prognostic significance. Although ACPA remains the strongest predictor of erosive progression, up to one-third of seronegative patients develop erosions within five years. The 2010 ACR/EULAR criteria may delay diagnosis in SNRA. Cytokine inhibitors and JAK inhibitors show largely serostatus-independent efficacy, whereas B-cell and T-cell–targeted therapies demonstrate attenuated responses in SNRA. Conclusions: SNRA is clinically and immunologically diverse. Integrating the AMPA framework is essential for refining classification and prognostication. Distinguishing erosive from non-erosive forms may guide treatment, while future work should prioritise biomarkers predicting progression and therapeutic response. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint damage. Although serum biomarkers such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) are widely used, blood-based testing is invasive. Saliva has emerged as a noninvasive diagnostic medium with clinical potential. This study aimed to evaluate the potential utility of salivary calprotectin and anti-CCP antibodies for discriminating patients with RA from healthy controls. Methods: Saliva samples were collected from 58 RA patients and 50 healthy controls. Salivary calprotectin and anti-CCP antibody levels were quantified using enzyme-linked immunosorbent assay. The diagnostic performance was evaluated using receiver operating characteristic curve analysis and logistic regression models that incorporated both biomarkers and clinical variables. Results: Patients with RA exhibited significantly higher salivary calprotectin and anti-CCP levels than controls (both p < 0.001). Calprotectin showed high sensitivity (79.31%), whereas anti-CCP displayed high specificity (84.00%). Salivary calprotectin was associated with disease duration and joint damage, while anti-CCP correlated with the erythrocyte sedimentation rate, RF, and serum anti-CCP. A multivariate model combining salivary biomarkers with clinical factors indicated an excellent diagnostic discrimination. Conclusions: Salivary calprotectin and anti-CCP antibodies show potential as complementary noninvasive biomarkers for distinguishing patients with established RA from healthy controls. However, as saliva samples were not collected at the time of initial diagnosis, these findings primarily support disease discrimination rather than early detection. Further prospective studies involving newly diagnosed and at-risk populations are required to clarify their role in early diagnosis, monitoring, and clinical implementation. Full article

Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized primarily by symmetrical small joint inflammation and damage, often accompanied by anti-cyclic citrullinated peptide (ACPA) and rheumatoid factor (RF) positivity. While conventional imaging modalities such as plain radiographs, ultrasound (US), and magnetic resonance imaging (MRI) are widely used to assess articular and some extra-articular manifestations, each presents limitations in terms of accessibility, comprehensiveness, and diagnostic scope. Nuclear imaging techniques, including positron emission tomography (PET), scintigraphy, and single-photon emission computed tomography (SPECT), offer whole-body imaging capabilities and the potential to simultaneously detect multi-system involvement, making them uniquely suited to the complex, systemic nature of RA. This review explores the current and potential roles of nuclear imaging in RA, highlighting its advantages in detecting both articular and extra-articular disease and its emerging promise as a routine tool in RA management. Full article

Background and Objective: Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting synovial joints including the temporomandibular joint (TMJ). This study aimed to assess the prevalence and characteristics of temporomandibular disorders (TMDs) in RA patients and correlate these findings with disease activity markers. Materials and Methods: This cross-sectional study included 40 RA patients meeting the 2010 ACR/EULAR criteria and 40 healthy subjects (HSs). Research diagnostic criteria for TMD were used to assess TMD. RA severity was evaluated using ESR, CRP, rheumatoid factor (RF), anti-CCP antibodies, Disease Activity Score (DAS) 28, and disease duration. Results: TMD prevalence was significantly higher in RA patients (75%) than in HS. Orofacial pain was a predominant TMD reported in 82.5% of RA patients. In RA patients there was a difference in myofascial pain, TMJ pain, and TMJ sounds in comparison to HS. All masticatory muscles were painful on palpation in RA patients and the pain intensity was higher in RA than in HS. The most painful muscles were the medial pterygoid muscles, the anterior belly of digastric muscle, and the tendon of the temporal muscle. Slight crepitations were the most frequent. Maximal active mouth opening was reduced and negatively correlated with CRP levels. The most frequent jaw function limitations were chewing and yawning difficulties and tinnitus. There were no correlations between TMD and DAS, RF, and disease duration. Conclusions: Active inflammation in RA is a crucial factor reducing mouth opening. TMD screening independent of disease duration should be integrated into RA management protocols, particularly for patients with elevated inflammatory markers, to eliminate other pathological factors contributing to faster TMJ functional changes, TMJ involvement, and the severity of TMD during RA course. Full article

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis. In addition, 60–80% of patients express anti-citrullinated protein antibodies (ACPAs), which serve as a diagnostic marker for RA. The effector functions of these autoantibodies can be heavily affected by the N-glycosylation of their Fc region. Here we present a comparison of the Fc N-glycosylation of ACPA IgG to that of non-ACPA IgG from the same patients, and of healthy controls, in an IgG isoform-specific manner. We isolated ACPA and normal serum IgG, digested by trypsin, and separated the resulting peptide mixture by a reversed-phase nanoLC coupled to a Bruker Maxis II Q-TOF, and determined the relative abundance of glycoforms. The paired analysis of galactosylation and sialylation of the IgG subclasses of ACPA and non-ACPA IgG has shown a significant, moderate negative correlation with the inflammatory markers, the level of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as with rheuma-factor (RF), but not with the disease activity score (DAS) or cyclic citrullinated peptide specific antibodies (anti-CCP). However, we detected a significant negative correlation between glycosylation and DAS in the non-ACPA IgG fractions. Furthermore, the isoform-specific analysis revealed additional insight into the changes of the glycosylation features of IgG in RA: changes in the frequencies of the bisecting GlcNAc unit between sample groups could be explained by only the IgG1 isoform; while invariance in fucosylation is the result of the superposition of two isoforms with opposite changes. These results highlight the importance of analyzing immunoglobulin glycosylation in an isoform-specific manner. Full article

Introduction. The Italian Committee for Tailored BIOlogic Therapy (ITABIO), in a first report, has reviewed the literature to identify the best strategy for the choice of second-line biologic therapy in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). To verify the application of ITABIO recommendations in real life and how the recommendations perform in maintaining the health status of patients affected by inflammatory arthritis (RA, SpA, PsA), a database has been developed by Pharmaceutical Governance to evaluate the appropriateness of prescriptions. Methods. We have analyzed retrospectively 616 patients, 288 (46.7%) affected by RA, 117 (19%) affected by SpA, and 211 (34.3%) affected by PsA. Age, sex, diagnosis, current treatment, previous treatments with csDMARDs, b-DMARDs, ts-DMARDs, presence of risk factors for cardiovascular (CV) events, liver disease, infections, extra-articular manifestations such as interstitial lung disease (ILD) for RA, enthesitis, dactylitis, uveitis, inflammatory bowel disease for SpA and PsA, neoplasms, diabetes, presence or absence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) for RA were evaluated. Results. The percentage of treatments with anti-TNF biosimilars was 65.1, 52.4, and 24.3% in SpA (76 patients(pt)), PsA (110 pt), and RA (69 pt), respectively. The percentage of monotherapy was 68% (418 pt) in the three diseases. For RA, 34.2% of patients were difficult to treat (D2T) (98 pt), 54.8% (157 pt) were in monotherapy (tocilizumab-sarilumab-upadacitinib-filgotinib). Abatacept was the most prescribed treatment in RF and ACPA-positive patients and in those with ILD. The anti-IL-17A secukinumab was prescribed in 12% of SpA, of which 71% had enthesitis and dactylitis (14 pt). Ixekizumab was prescribed in 10.4% of PsA patients over 65 years with previous CV events, enthesitis, and dactylitis (21 pt). Apremilast was present in 71% of PsA with previous cancer. Conclusions. The cross-sectional analysis of prescriptions in patients with RA, SpA, and PsA demonstrates how the ITABIO recommendations can guide towards the correct appropriateness of prescription. RA and especially D2T-RA remains the disease with the greatest therapeutic failures, with the highest percentage of monotherapy (anti-IL-6 and Jak-i) and of discontinuation of MTX. Full article

Background and Objectives: Psoriatic arthritis (PsA) is a chronic rheumatic disease that is frequently associated with fibromyalgia (FM). The coexistence of FM complicates the evaluation of PsA disease activity and the planning of treatment strategies, as the two conditions share many overlapping clinical symptoms. To investigate the contribution of demographic factors and available serum biomarkers of inflammation and autoimmunity in characterizing the heterogeneity among patients meeting the classification criteria for both PsA and FM. Materials and Methods: This cross-sectional, single-center study involved 1547 adult patients evaluated between January 2017 and December 2024 who met the CASPAR criteria for PsA. A patient subgroup also met the 2016 ACR criteria for FM. Demographic data, serum inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and autoimmunity markers including antinuclear antibodies (ANA), rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPA) were evaluated. Statistical analyses included chi-square tests, t-tests, Mann–Whitney U tests, and multivariate logistic regression to identify independent predictors associated with the coexistence of PsA and FM. Results: A total of 254 patients (16.42%) were diagnosed with concomitant FM. Compared to patients with PsA alone, those with concurrent PsA and FM showed significantly lower C-reactive protein (CRP) levels (0.39 ± 0.74 vs. 2.88 ± 12.31 mg/dL; p < 0.001) and a higher frequency of antinuclear antibody (ANA) positivity (13.57% vs. 5.78%; p < 0.001). No significant differences were observed in rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA) positivity between the groups. Multivariate logistic regression identified female sex, ANA positivity, CRP levels ≤ 0.5 mg/dL, and elevated body mass index (BMI) as independent predictors of the presence of concomitant FM. Conclusions: Patients with concomitant PsA and FM have a distinct demographic and serological profile, suggesting the existence of a clinically significant subgroup within the PsA population. Recognition of these differences may improve diagnostic accuracy and support the development of personalized, non-immunosuppressive therapeutic strategies for this subgroup of patients. Full article

Background: Addison’s disease (AD) is a rare disorder that often develops in the context of autoimmune polyglandular syndromes. However, the prevalence of rheumatological autoimmune diseases and corresponding autoimmune markers in AD is poorly investigated. Therefore, the present study aims to explore systemic and organ-specific immune markers in a cohort of AD patients from a single tertiary endocrine center. Material and methods: In total, 43 adult AD patients and 31 controls were included in the study. 21-hydroxylase autoantibodies (21OHAb), glutamic acid decarboxylase autoantibodies (GADAbs), zinc transporter-8 autoantibodies (ZnT8Abs), antibodies against nuclear antigens (ANAs), autoantibodies against cyclic citrullinated peptides (CCPAbs), rheumatoid factors (RFs), IgG autoantibodies against cardiolipin (ACLAbs), and autoantibodies against beta-2-Glycoprotein I (β2-GPIAbs) were measured in all participants. Results: An increased prevalence of antibodies against RFs (27.91% vs. 0%, p < 0.001) and ANAs (13.95% vs. 0%, p = 0.037) was found in AD patients compared to controls. Moreover, the titers of 21-hydroxylase and RF antibodies correlated positively (r = +0.269, p = 0.020). The AD patients tended to show an increased prevalence of subthreshold ACL antibody reactivity compared to controls. All patients diagnosed with type 1 diabetes mellitus were GADAb- but not ZnT8Ab-positive. Conclusions: The results show an increased prevalence of ANA and RF positivity in AD patients compared to controls and a significant association between 21-OHAb and RF positivity. ZnT8Ab positivity was not typical for adult AD patients from our ethnic group, while GADAbs were an essential marker for autoimmune diabetes mellitus. Extensive studies in different ethnic groups are needed to establish the clinical significance of various immunological markers for AD comorbidity and the appropriate follow-up protocols for patients with different antibody positivity. Full article

The aim of the paper was to characterize rheumatoid factor IgA, IgG, and IgM isotypes in patients with Sjögren’s syndrome (SS) subsets, based on the absence or presence of joint complaints of different etiologies. In total, 164 SS patients were grouped based on whether they had polyarthritis as an extraglandular manifestation (n = 73, SS+pa), rheumatoid arthritis as an associated autoimmune disorder (n = 46, SS+RA), or Sjögren’s syndrome without inflammatory joint pain (n = 45, SS). The highest IgA rheumatoid factor isotype levels were detected in SS patients, whereas the lowest levels were found in the SS+RA group, without a significant difference. Neither IgG nor IgM RF differed significantly between the patient subclasses. In addition to other disease-specific markers, seropositive patients who were seropositive for any RF isotype were significantly more frequently anti-Ro/SS-A and anti-La/SS-B positive and had higher ESSDAI levels. In SS and SS+pa patients, a strong negative correlation was observed between IgA RF and age, whereas a strong positive correlation was found between IgA RF and ESSDAI, RF, IgA, IgG, anti-Ro/SS-A, and anti-La/SS-B levels. High total IgG levels together with high IgA RF levels occurred most frequently in SS patients (p = 0.05), whereas the combination of normal IgG and high IgM RF was significantly more frequent in the SS+RA group. The co-occurrence of high total IgG and normal IgM RF did not differ significantly between the patient subsets; however, this was the combination with the highest sensitivity (94.5%) for SS+pa patients. Based on our findings, rheumatoid factor isotypes have an additive value in the differentiation of non-erosive polyarthritis and erosive rheumatoid arthritis during the disease course of patients with Sjögren’s syndrome. All rheumatoid factor isotypes predict a more severe disease course, but IgA RF may serve as a candidate for being an early, poor prognostic factor for SS patients. Full article

Background: Numerous studies have found higher levels of autoantibodies including anti citrullinated protein antibodies (ACPAs), anti-cyclic citrullinated peptides (aCCP), or rheumatoid factor (RF) against periodontal microorganisms in rheumatoid arthritis (RA). Objective: To evaluate the correlation between periodontal bacteria and RA disease parameters. Methods: We utilized PubMed, Scopus, ScienceDirect, and manual search databases up until March 2024 using PRISMA 2020 guidelines. The data were obtained from microbiological assays by RT-PCR/qPCR, sequencing, and serological testing of disease parameters (ACPA, aCCP, and RF) utilizing ELISA method. Results: A total of 1514 documents were discovered based on the inclusion criteria. Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella_9 were associated with elevated levels of ACPA/aCCP and RF in RA with periodontitis. A positive correlation was found between Peptococcus simiae, Aminipila butyrica, Leptotrichia spp., Leptotrichia wadei, and Neisseria bacilliformis with ACPA, and Treponema sp. canine oral taxon 087 with RF. Conclusions: This study found that several oral microorganisms correlate with elevated ACPA/aCCP and RF in RA with periodontitis. Future studies of the oral microbiome and the molecular mechanisms are anticipated to discover new therapies and diagnostic methods for periodontitis and RA. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a representative systemic autoimmune rheumatic disease (SARD) characterized by synovial inflammation. While antinuclear antibodies (ANAs) positivity in patients with RA varies widely, the relationship between ANA patterns and clinical features remains unclear. This study aimed to evaluate the clinical significance of ANA in patients with RA. Methods: This single-center RA registry study included 814 Japanese patients after excluding those with coexisting SARDs. ANA titers and staining patterns were assessed by indirect immunofluorescence assays on HEp-2 cells. Clinical and laboratory features were analyzed, and logistic regression was used to identify risk factors for pulmonary involvement. Hierarchical clustering and statistical analyses were performed to explore associations between ANA patterns and clinical features. Results: ANA positivity was observed in 41.5% of patients, with the speckled and homogeneous patterns being the most common. ANA-positive patients exhibited significantly higher rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) positivity rates and titers, along with elevated disease activity markers, including Evaluator’s Global Assessment and Swollen Joint Count. Nucleolar pattern positivity was independently associated with pulmonary complications, predominantly interstitial lung disease, and higher rates of JAK inhibitor use. Discrete-speckled pattern-positive patients exhibited high ANA titers but lower RF and ACPA levels, reflecting a distinct subset of RA. Conclusions: ANA staining patterns and titers are clinically relevant in RA, with nucleolar and discrete-speckled patterns indicating distinct clinical and pathophysiological profiles. ANA should be interpreted alongside other serological markers and clinical parameters rather than as a standalone tool. Further studies are needed to refine its clinical applicability and integration into RA management. Full article