Longitudinal Analysis of Somatic Mosaicism and Clonal Hematopoiesis in Cryopyrin-Associated Periodic Syndrome.

Objective: Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory disease caused by gain-of-function mutations in NLRP3. Although somatic NLRP3 mosaicism is increasingly recognized, it remains unclear how variant allele frequency (VAF) changes over time and whether disease onset age reflects differences in somatic mutation dynamics. This study aimed to analyze the longitudinal VAF trends and their correlation with clonal hematopoiesis (CH) in patients with CAPS mosaicism.

Roles of JAK-STAT signaling and granulocyte-macrophage colony-stimulating factor in the development of osteitis and bone microstructure changes in rheumatoid arthritis.

Background: Osteitis on magnetic resonance imaging (MRI) and bone microstructure changes (BMC) on high-resolution peripheral quantitative computed tomography (CT) are the earliest signs of arthritis, preceding the development of bone erosion on X-ray in rheumatoid arthritis (RA). Recently, a Janus kinase (JAK) inhibitor, baricitinib, reportedly suppresses these early changes. This study aimed to elucidate the underlying molecular mechanism of osteitis and BMC using an animal model of RA and human samples.

Serum cytokine levels towards precision medicine in Still's disease: a subanalysis of a randomized controlled trial of tocilizumab.

Objectives: To predict the efficacy of IL-6 inhibition in patients with Still's disease by analysing inflammatory cytokine profiles before and during an IL-6 receptor inhibitor therapy.

Methods: This is a subanalysis of the 52-week, randomized, double-blind, placebo-controlled trial of tocilizumab, an IL-6 receptor inhibitor, in patients with Still's disease. Multiple serum cytokine levels were measured regularly, and their pattern and profiles were analysed based on the response to tocilizumab.

Immune checkpoint inhibitor-induced myocarditis and multiple adverse events with pre-existing rheumatoid arthritis: a case report and literature review.

Immune checkpoint inhibitors (ICIs) can trigger immune-related adverse events (irAEs) and rheumatoid arthritis (RA) reactivation in cancer patients with pre-existing RA. Studies indicate RA reactivation occurs in approximately 50% of these patients, while new irAEs develop in 25-50% of ICI-treated patients. Furthermore, ICI-induced myocarditis has been reported to have a high mortality rate, ranging from 25% to 50%.

Dried blood spot proteome identifies subclinical interferon signature in neonates with type I interferonopathy.

Background: Type I interferonopathy is characterized by aberrant upregulation of type I interferon signaling. The mRNA interferon signature is a useful marker for activation of the interferon pathway and for diagnosis of type I interferonopathy; however, early diagnosis is challenging.

Objective: This study sought to identify the proteomic interferon signature in dried blood spot (DBS) samples.

ICOS+CD4+ T cells define a high susceptibility to anti-PD-1 therapy-induced lung pathogenesis.

Managing immune-related adverse events (irAEs) caused by cancer immunotherapy is essential for developing effective and safer therapies. However, cellular mechanism(s) underlying organ toxicity during anti-PD-(L)1 therapy remain unclear. Here, we investigated the effect of chronological aging on anti-PD-(L)1 therapy-induced irAE-like lung toxicity, utilizing tumor-bearing aged mice.

Predicting rheumatoid arthritis progression from seronegative undifferentiated arthritis using machine learning: a deep learning model trained on the KURAMA cohort and externally validated with the ANSWER cohort.

Background: Undifferentiated arthritis (UA) often develops into rheumatoid arthritis (RA), but predicting disease progression from seronegative UA remains challenging because seronegative RA often does not meet the classification criteria. This study aims to build a machine learning (ML) model to predict the progression from seronegative UA to RA using clinical and laboratory parameters.

Methods: KURAMA cohort (training dataset) and ANSWER cohort (validation dataset) were utilized.

Comparative effectiveness of subcutaneous sarilumab 200 mg biweekly, subcutaneous Tocilizumab 162 mg biweekly, and intravenous Tocilizumab 8 mg/kg every 4 weeks in patients with rheumatoid arthritis: a prospective cohort study.

Background: While targeting the interleukin-6 receptor (IL-6R) through the use of sarilumab (SAR) or tocilizumab (TCZ) has become a major therapeutic approach for rheumatoid arthritis (RA), direct comparisons between IL-6R inhibitors (IL-6Ris) for treating RA have not been conducted. We aimed to compare the effectiveness of subcutaneous sarilumab (SAR-SC), subcutaneous tocilizumab (TCZ-SC), and intravenous TCZ (TCZ-IV) against RA in a multicenter cohort study.

Methods: Within the target trial emulation framework, an incident new-user and active-comparator cohort design was used.

Anti-arthritic effects of polyunsaturated fatty acid-rich supplementation combined with selective soluble epoxide hydrolase inhibitors in a collagen-induced arthritis mouse model.

Objectives: Polyunsaturated fatty acids (PUFAs) are healthy fats that contain a double carbon bond. They are made up of omega (ω)-3 and ω-6 PUFAs, where ω-3 PUFAs exhibit beneficial effects, such as the suppression of cardiovascular events and the improvement of abnormal lipid metabolism. However, their effects on rheumatoid arthritis (RA) are unclear.

Memory B cells and their transcriptomic profiles associated with belimumab resistance in systemic lupus erythematosus in the maintenance phase.

The factors contributing to the treatment efficacy of belimumab in patients with systemic lupus erythematosus (SLE) in the maintenance phase are unknown. Here, we collected blood samples from patients with SLE (n=44) treated with belimumab before and three and six months after treatment. RNA-Seq of whole blood was performed, and gene expression was quantified.

Factors Associated With Hallux Valgus Progression in Patients With Rheumatoid Arthritis: Insights From Non-Weight-Bearing Radiographs in the KURAMA Cohort.

Objectives: This longitudinal study investigated the factors associated with hallux valgus (HV) progression in patients with rheumatoid arthritis (RA).

Methods: We included 316 patients with RA who underwent foot radiography in 2015 and more than four years later. The HV angle (HVA), first-second intermetatarsal angle (IMA), first-fifth intermetatarsal angle (M1/M5 angle), and calcaneal pitch (CP) angle were measured.

Beneficial effects on T cells by photodynamic therapy with talaporfin enhance cancer immunotherapy.

Photodynamic therapy (PDT), a local cancer treatment using photosensitizers, has been reported to enhance antitumor immune responses by inducing immunogenic cell death. Although several studies have demonstrated the synergistic antitumor effects of PDT and immune checkpoint blockage (ICB), the detailed underlying mechanisms remain poorly understood. In this study, we investigated the immunological effects of PDT with talaporfin (Tal-PDT), a clinically approved photosensitizer, using bilateral tumor-bearing mouse models.

Prediction models incorporating second metacarpal cortical index for osteoporosis in rheumatoid arthritis: Externally validated machine learning models developed using data from the KURAMA cohort.

Objective: Osteoporosis and osteopenia are significant concerns in rheumatoid arthritis (RA), predisposing patients to fragility fractures. While dual-energy X-ray absorptiometry (DXA) is the gold standard for bone mineral density (BMD) assessment, simpler screening tools are needed. This study aims to assess the correlation between the second metacarpal cortical index (2MCI) and BMD in RA patients, and to evaluate machine learning (ML) models utilizing 2MCI and clinical parameters for predicting osteoporosis/osteopenia presence and BMD.

Factors affecting discrepancies in disease activity evaluation between patients and physicians in systemic lupus erythematosus-The importance of symptoms such as fatigue.

Objectives: There are often discrepancies in the evaluation of disease activity between patients and physicians in systemic lupus erythematosus (SLE). In this study, we examined the factors that affect those evaluations.

Methods: Physician visual analogue scale (Ph-VAS), patient VAS (Pt-VAS), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k), glucocorticoid (GC) usage and dose, age, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and three patient-reported outcomes (SLE symptom checklist [SSC], short-form 36 questionnaire [SF-36], and LupusPRO) were obtained from a study performed in 2019 using 225 SLE outpatients of the Kyoto Lupus Cohort at Kyoto University Hospital.

Subjective symptoms are triggers for the detection of immune checkpoint inhibitor-induced interstitial lung disease and associate with disease severity: a single-center retrospective study.

Background: Interstitial lung disease (ILD) is one of the most common fatal immune-related adverse events (irAEs). ILD development adversely affects the continuation of anticancer drug therapy, including immune checkpoint inhibitor (ICI) therapy and prognosis. There are no established useful clinical indicators for the early detection of ILD.

A case of vesiculobullous dermatomyositis with anti-NXP-2 antibody without malignancy.

Vesiculobullous dermatomyositis (VD) is a rare manifestation of dermatomyositis (DM) and has been suggested to be associated with malignancy. Although the myositis-specific autoantibodies are associated with distinct clinical presentations of DM, those associated with VD remain unclear. Here, we present the case of a 54-year-old man with VD who tested positive for antinuclear matrix protein 2 (NXP-2) antibodies, one of the DM-specific autoantibodies.

Effects of IL-6, JAK, TNF inhibitors, and CTLA4-Ig on knee symptoms in patients with rheumatoid arthritis.

This study aims to identify factors influencing the alleviation of knee joint symptoms in patients with rheumatoid arthritis treated with biologic or target synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Among 2321 patients who started b/tsDMARDs between 2010 and 2023, we focused on 295 patients who had knee swelling or tenderness at the initiation of b/tsDMARDs and continued b/tsDMARDs at least 3 months, with recorded knee symptoms 6 months later. Symptom relief after 6 months was 78.

Active Rheumatoid Arthritis and Scoliosis: A Mid-Term Cohort Study.

Study Design: Retrospective cohort study.

Objective: To elucidate the factors related to the progression of scoliosis in patients with rheumatoid arthritis (RA) using longitudinal cohort data.

Background: Of patients, 30% with RA have lumbar scoliosis.

Safety of Janus kinase inhibitors compared to biological DMARDs in patients with rheumatoid arthritis and renal impairment: the ANSWER cohort study.

Data on the safety of Janus kinase inhibitors (JAKis) in patients with renal impairment are lacking. This study aimed to investigate the safety of JAKis compared to biological (b) DMARDs in patients with rheumatoid arthritis (RA) and renal impairment. We used a multi-centre observational registry of patients with RA in Japan (the ANSWER cohort).

Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.

Objectives: To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biologic DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi).

Methods: Retrospective analysis was conducted on data from the ANSWER cohort comprising 3623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention.

Low Hounsfield unit values on computed tomography as a potential predictor of vertebral fracture in patients with rheumatoid arthritis: The KURAMA cohort study.

Objective: Hounsfield units (HU) measured using computed tomography (CT) have gained considerable attention for the detection of osteoporosis. This study aimed to investigate whether opportunistic CT could predict vertebral fractures in patients with rheumatoid arthritis (RA).

Methods: A total of 233 patients with RA who underwent chest CT were included in this study.