ACR open rheumatology最新文献

Objective: Severalstudies have highlighted the role of Type I interferons (IFN-I) in activating inflammatory pathways in lupus. However, no previous research focused on investigating the role of IFN-I gene expression in the ophthalmologic involvement of systemic lupus erythematosus (SLE). We aimed to assess the association between the IFN-I gene signature and ophthalmologic involvement in SLE.

Methods: Cross-sectional study includes patients ≥18 years old, fulfilling the 2019 EULAR or American College of Rheumatology criteria for SLE. Ophthalmologic evaluation, the Systemic Lupus Erythematosus Disease Activity Index-2K index, and blood sample collection were performed at the time of study assessment. Peripheral blood mononuclear cells were isolated, RNA was extracted, and complementary DNA was synthesized. Gene expression of IFI27, IFI44L, IFIT1, ISG15, RSAD2, and SIGLEC1 was assessed by real-time polymerase chain reaction, using RPLP0 and EEF1A1 as reference genes for normalization. The median normalized relative quantity of the genes for each patient was used to calculate the fold change (FC) of the "Interferon Score." Group comparisons were conducted using the Mann-Whitney U test, and correlations between variables were assessed using Spearman's rank correlation coefficient.

Results: We included 32 patients with SLE. Ocular involvement occurred in 62.5%, either due to aqueous-deficient dry eye (46.88%) or lupus retinopathy. A higher expression of the IFN-I gene was found in patients with ocular involvement (FC = 2.52 ± 1.96; P = 0.0027) compared with those without ophthalmologic changes.

Conclusion: The upregulation of the IFN-I gene expression was associated with ophthalmologic involvement in SLE, potentially playing a role in its pathogenesis.

Objective: To investigate longitudinal trends in rheumatoid arthritis (RA) diagnosis and monitoring by physicians and advanced practice providers (APPs) as measured by laboratory testing.

Methods: We conducted a retrospective review of RA-associated diagnostic and monitoring tests ordered through Labcorp by 7,026 physicians and 2,188 APPs in primary care and rheumatology between 2012 and 2024. Diagnostic tests include conventional markers (rheumatoid factor and anti-cyclic citrullinated peptide) and emerging markers (14.3.3 eta protein, anti-citrullinated α-enolase peptide 1, anti-carbamylated protein, and anti-citrullinated vimentin antibodies). Panel tests combine these markers to enhance diagnostic accuracy. Monitoring tests include the Vectra tests.

Results: From 2012 to 2024, rheumatology APPs who consistently ordered RA-associated tests annually through Labcorp increased by 411.8%, whereas rheumatology physicians who consistently ordered RA-associated tests through Labcorp grew by 58.5%. Compared with rheumatology physicians, rheumatology APPs ordered 37.9 fewer conventional markers (P = 2.7 × 10^-12) and 2.4 more monitoring tests (P = 0.019). Between 2012 and 2024, conventional marker volumes increased by 3.0% among rheumatology physicians, 98.9% among rheumatology APPs, 36.2% among primary care physicians, and 75.6% among primary care APPs. The yearly average volume of RA panel tests ordered by rheumatology APPs increased by 2,948.5% compared with increases of 218.4% by rheumatology physicians, 128.0% by primary care physicians, and 203.7% by primary care APPs. The difference in the proportion of positive diagnostic test results between rheumatology physicians and rheumatology APPs narrowed from 3.0% in 2015 to 0.5% in 2024.

Conclusion: We observed a rise in APP contributions to RA-diagnostic and RA-monitoring test ordering, consistent with their growing presence within the rheumatology workforce.

Objective: Transcript and protein abundance data were measured to compare biologic pathway effects in the peripheral blood of patients diagnosed with systemic lupus erythematosus (SLE) and dermatomyositis (DM) who receive immunosuppressive therapies.

Methods: Expression data from the peripheral blood of patients with SLE (n = 41) and DM (n = 14) were obtained using one transcriptomic and two proteomic platforms and compared with matched healthy control subjects. Regulatory effects were integrated across the three platforms to assess biologic pathways and downstream signaling, within and across disease cohorts.

Results: Expressions of 973 gene loci were altered overall, with 67 genes shared in SLE and DM, including interferon (IFN) markers ISG15, CXCL10, OAS1, and STAT1, and other markers of cell adhesion, immune signaling, and apoptosis. A total of 24 of 32 (75%) pathways were shared in SLE and DM, including granulocyte adhesion, immune cell migration, acute-phase response, apoptosis, and L1CAM signaling. However, SLE peripheral blood exhibited distinctive activation of Type I IFN through increased ligand-receptor interactions not widely elevated in DM. Blood from patients with DM distinctly showed substantially increased expression of intracellular kinases and associated downstream signaling molecules.

Conclusion: Using a multienrichment analytic approach that integrated multiple transcriptomics and proteomics platforms, common underlying immune pathways were identified in SLE and DM. Additionally, two distinctive molecular mechanisms persisted in each condition: IFN signaling was distinctly up-regulated in patients with longstanding SLE, whereas intracellular signaling, particularly kinases, were unique to DM. These shared and distinct findings highlight potential therapeutic opportunities driven by underlying molecular mechanisms.

Objective: Systemic lupus erythematosus (SLE) commonly affects women during their childbearing years, making pregnancy experiences especially important to understand. This is particularly true for US Hispanic women, who face a higher SLE burden, more unplanned pregnancies, and frequent language or cultural discordance with clinicians. This study explores their perspectives, focusing on emotional dualities, logistical challenges, and views on unplanned pregnancies.

Methods: We conducted semistructured interviews with 30 Hispanic women aged 18 to 45 with SLE, recruited from Los Angeles General Medical Center and LupusLA. Eligible participants were heterosexually active or considering pregnancy within three years. Interviews were analyzed using grounded theory to identify themes related to pregnancy experiences, whether actual or hypothetical.

Results: Three core themes emerged: (1) pregnancy with SLE was marked by a variety of emotions (primarily hope and anxiety); (2) navigating frequent appointments and complex care created logistical strain but also reassurance; and (3) unplanned or poorly timed pregnancies led to a desire for immediate, trusted guidance from their rheumatologist, with most participants preferring continuation if medically feasible.

Conclusion: Findings highlight the emotional complexity and logistical challenges faced by Hispanic women with SLE. Many of the themes mirror those seen in other chronic disease populations, underscoring that US Hispanic women with SLE, their cultural and linguistic barriers notwithstanding, share many of the same hopes, fears, and needs as other women navigating pregnancy with chronic illness. These results emphasize the need for empathetic, patient-centered reproductive health care that addresses their emotional, medical, and informational needs.

Objective: The aim was to describe the percentage of patients with axial spondyloarthritis (axSpA), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) in the Rheumatology Informatics System for Effectiveness (RISE) Registry who received a rehabilitation referral.

Methods: Data were derived from RISE, an electronic health record enabled registry of approximately 30% of the US clinical rheumatology workforce. Practices were eligible if there was at least one patient record indicating a referral to rehabilitation (physical or occupational therapy) in any plan of care. Patients from eligible practices were included if they were ≥18 years old, had two or more qualifying International Classification of Disease (ICD) codes for axSpA, RA, or SLE at least 30 days apart, and had at least one visit in 2022. The primary outcome was percentage of patients with at least one rehabilitation referral documented in 2022 and at any time, reported by patient and practice characteristics.

Results: A total of 20,574 adult patients with axSpA, 198,517 with RA, and 37,060 with SLE were identified. In 2022, 4.4%, 2.7%, and 2.6% of patients with axSpA, RA, and SLE were referred to rehabilitation at least once, whereas 11.8%, 9.2%, and 8.7% of these patients received a referral to rehabilitation at any time, respectively. Among practices, 52%, 61%, and 60% of practices referred <1% of patients with axSpA, RA, and SLE to rehabilitation in 2022.

Conclusion: Rehabilitation referral from rheumatology practices was low, with considerable variation across practices. The strength of recommendations for rehabilitation in treatment guidelines seem to have limited impact on referral practices.

Objectives: To evaluate persistence, outcomes, safety, and remission maintenance after switching from intravenous infliximab (IV-IFX) to subcutaneous infliximab (SC-IFX, CT-P13) in patients with Takayasu arteritis (TA).

Methods: We conducted a prospective, single-center, proof-of-concept observational study of consecutive adults with TA in sustained clinical, laboratory, and positron emission tomography (PET) remission switched from stable 5 mg/kg dose IV-IFX to SC-IFX 120 mg every two weeks. Assessments at baseline, 6 months, and 12 months included Indian Takayasu Clinical Activity Score (ITAS2010), Disease Extent Index-Takayasu (Dei.TAK), PET Vascular Activity Score (PETVAS), C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), Large Vessel Vasculitis Index of Damage (LVVID), and safety data. The primary objective was 12-month drug persistence. Secondary outcomes included remission rates, changes in ITAS2010, Dei.TAK, PETVAS, acute-phase reactants, damage accrual, and safety.

Results: Nine women (median age 35 [interquartile range (IQR) 28-44] years) were included. The median IV-IFX exposure before the switch was 60 (IQR 24-72) months. Twelve-month drug persistence was 77.8%. One patient discontinued early due to an injection-site reaction, and another experienced a relapse at 12 months that required a therapy change. At 12 months, 87.5% (seven of eight) patients remained in remission. CRP and ESR remained stable (P = 0.297 and P = 0.068, respectively). PETVAS was similar to pre-switch values (P = 0.589). Median LVVID remained stable throughout follow-up. No serious adverse events occurred.

Conclusions: IV-IFX to SC-IFX switching was feasible and well tolerated and generally maintained remission over 12 months in most patients with TA, with stable metabolic imaging and no increase in damage accrual. These findings support SC-IFX as a practical maintenance strategy, warranting confirmation in larger multicenter cohorts.

Objective: Emerging evidence suggests that apolipoprotein E (apoE) may be involved in the immune system and diseases driven by chronic inflammation. The impact of the full range of structural genetic variation in APOE for risk of rheumatoid arthritis, psoriasis, and psoriatic arthritis in the general population is not known. Further, whether apoE is associated with the common blood inflammatory biomarker profile warrants characterization.

Methods: We systematically sequenced APOE in 10,369 individuals from the Copenhagen City Heart Study (CCHS) and genotyped nine variants (frequency ≥ 2/10,369) in 95,228 individuals from the Copenhagen General Population Study (CGPS). The UK Biobank was used for validation of the observed associations between the ε2/ε3/ε4 APOE polymorphism and disease end points.

Results: Concentrations or cell counts decreased stepwise from ε33 to ε43 to ε44 for C-reactive protein (P = 4 × 10^-223), eosinophils (P = 5 × 10^-5), monocytes (P = 8 × 10^-4), complement C3 (P = 0.001), and fibrinogen (P = 0.009). The multifactorially adjusted hazard ratio (HR) for ε32 versus ε33 was 0.81 (95% confidence interval [CI] 0.70-0.94) for rheumatoid arthritis in CCHS+CGPS. Similarly, the HR for ε32 versus ε33 was 0.88 (95% CI 0.79-0.99) for psoriasis in a meta-analysis of CCHS+CGPS and the UK Biobank.

Conclusion: We found that APOE ε4 is associated with a biomarker profile consistent with a decreased general immune response. The ε32 genotype is associated with an intermediate biomarker profile and with a decreased risk of rheumatoid arthritis in the Copenhagen cohorts and of psoriasis in the meta-analysis. This suggests that the low-risk combination of apoE3 and apoE2 may play a role in the normal noninjurious inflammatory response.

Objective: We evaluated the immunogenicity of SARS-CoV-2 mRNA vaccines in patients with juvenile idiopathic arthritis (JIA), focusing on the generation of spike-specific memory B cells (MBCs) and of neutralizing antibodies, and assessed the impact of disease-modifying antirheumatic drugs, particularly tumor necrosis factor inhibitors (TNFi).

Methods: This study enrolled 35 adolescent and young adult patients with JIA. Data concerning disease characteristics and SARS-CoV-2 vaccination and infection were collected. We analyzed the frequency of low-affinity spike-specific and high-affinity spike-specific MBCs by flow cytometry. We measured total anti-spike antibodies levels using a chemiluminescence microparticle immunoassay and assessed neutralizing antibody titers with a microneutralization assay.

Results: Patients with JIA showed a reduced frequency of high-affinity MBCs compared to controls, with a notably poorer response among those receiving TNFi treatment. Additionally, their ability to bind the Omicron variant was significantly lower, particularly among TNFi-treated patients. SARS-CoV-2 infection alone was not able to generate high-affinity MBCs and neutralizing antibodies in patients with JIA. After receiving three vaccine doses, 43% of patients with JIA exhibited a reduced frequency of high-affinity MBCs and neutralizing antibodies.

Conclusion: Patients with JIA undergoing treatment with TNFi demonstrated a diminished immunogenic response to SARS-CoV-2 vaccination, with lower frequencies of high-affinity MBCs and decreased neutralizing antibody titers. These findings underscore the need for customized vaccination protocols, including the potential use of booster doses, to enhance immunoprotection in this group. Additionally, the development of reliable biomarkers to distinguish between patients with and without adequate protective immunity is imperative to refine therapeutic interventions and ensure optimal patient outcomes.

Objective: Systemic sclerosis (SSc) is known to exhibit significant epidemiologic and clinical variation. This study aimed to describe the clinical and epidemiologic characteristics of SSc in Alaska Native and American Indian (AN/AI) individuals in Alaska.

Methods: Adults with a potential diagnosis of SSc were identified through an electronic health record query for SSc-related codes from 2012 to 2019 in the participating tribal health organizations in the Alaska Tribal Health System (ATHS). Detailed medical record abstraction was performed to confirm diagnoses and clinical characteristics, including demographics, SSc subtype, organ involvement, serologic test results, and medications. The denominator for prevalence was the 2019 ATHS user population aged ≥18 years.

Results: The age-adjusted prevalence of SSc was 354 (95% confidence interval [CI] 241-504) per 1,000,000 adults overall, 503 (95% CI 323-752) per 1,000,000 in women, and 188 (95% CI 82-379) per 1,000,000 in men. Of the 36 adults identified with SSc, the mean age at diagnosis was 59.9 years (median 62 years), with a female predominance (28 [77.8%]; female-to-male ratio 3.5:1). Diffuse SSc prevalence was 95 (95% CI 44-184), and limited SSc prevalence was 258 (95% CI 164-391) per 1,000,000. Although most clinical features appear to be similar to other populations, a high prevalence of pulmonary arterial hypertension, gastrointestinal manifestations, and telangiectasias were notable.

Conclusion: This is the first study to describe the epidemiology and clinical characteristics of SSc in AN/AI individuals in Alaska. The prevalence, average age at onset, female predominance, and most clinical features are generally similar to those in studies of SSc in other populations.

Objective: Diffuse cutaneous systemic sclerosis (dcSSc) is characterized by skin and internal organ fibrosis. The regulatory aspects of the immune system involved in maintaining tolerance are still poorly understood in dcSSc. The late checkpoint inhibitory lymphocyte activation gene 3 (LAG-3) is implicated in T cell inhibition by interacting with its ligand, major histocompatibility complex class II. Its role in dcSSc has yet to be established.

Methods: Plasma soluble LAG-3 (sLAG-3) levels of 35 patients with dcSSc were compared with the levels of 20 healthy controls (HCs). Peripheral blood mononuclear cell (PBMC) samples from patients with dcSSc (n = 8) and HCs (n = 8) were analyzed by flow cytometry for the surface expression of LAG-3 on CD4+ and CD8+ T cells after CD3/CD28 stimulation. The dcSSc PBMCs were stimulated (anti-CD3/CD28), kept as monocultures, or cocultured with autologous dermal fibroblasts and treated with a LAG-3 agonistic antibody or isotype control. The supernatants were analyzed for proinflammatory cytokines, extracellular matrix proteins, and bioactive type I interferon (IFN).

Results: Patients with dcSSc had a two-fold decreased sLAG-3 level compared with HCs (P < 0.0001). Increased surface expression of LAG-3 was observed in activated CD4+ T cells and CD8+ T cells in patients with dcSSc compared to HC PBMCs. The LAG-3 agonistic antibody decreased IFNγ, interleukin-4, and tumor necrosis factor α levels in supernatants from PBMCs and dermal fibroblast cocultures. Furthermore, we observed decreased pro collagen, fibronectin, and IFNα/β bioactivity in the cocultures.

Conclusion: LAG-3 is immunoregulatory in dcSSc, and a LAG-3 agonistic antibody is a potential treatment modality.