Stem-like and effector peripheral helper T cells comprise distinct subsets in rheumatoid arthritis.

Peripheral helper T (T) cells can play pathogenic roles in human autoimmune diseases. T cells are proposed to be the major B cell helpers in inflamed joints in rheumatoid arthritis (RA), but whether and how T cells are engaged in tissue inflammation remains unclear. We demonstrate that T cells comprise two subsets in RA: stem-like T (S-T) and effector T (E-T) cells.

Human CD4 T cells regulate peripheral immune responses in rheumatoid arthritis via insulin-like growth factor-like family member 2.

Human CD4 T cells play a central role in the pathogenesis of autoimmune diseases, but their immunoregulatory mechanisms driving pathogenesis remain to be elucidated. We show that human T peripheral helper cells (T cells) regulate peripheral immune responses via insulin-like growth factor-like family member 2 (IGFL2), an inflammatory factor found exclusively in primates. Single-cell RNA sequencing of seropositive rheumatoid arthritis (RA) synovium showed that is specifically expressed by CD4 T cells, predominantly T cells.

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.

A case of IgG4-related disease potentially triggered by COVID-19 vaccination: longitudinal serum IgG4 monitoring from prevaccination.

We report a case of a 64-year-old Japanese man who developed IgG4-related pericoronary arteritis following mRNA-based COVID-19 vaccination. The patient presented with anterior chest pain and imaging revealed perivascular soft tissue thickening around the coronary arteries, along with pancreatic enlargement, enlarged prostate, and periaortitis. Laboratory tests showed markedly elevated serum IgG4 levels (1740 mg/dl).

Concordance between treatment guideline and daily practice in the management of eosinophilic granulomatosis with polyangiitis: A cross-sectional web-questionnaire survey.

Objectives: To examine real-world clinical practices in the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) across Japan and evaluate concordance with national treatment guidelines.

Methods: A cross-sectional, web-based survey was conducted between February 14 and 19, 2024. Physicians from rheumatology, pulmonology, and neurology departments who had treated EGPA within the past 24 months were invited to complete a 17-item questionnaire.

Safety of glucocorticoid dose reduction in microscopic polyangiitis: a multicentre REVEAL cohort study.

Objectives: This retrospective, multicentre study evaluated the safety of reducing glucocorticoids in patients with microscopic polyangiitis (MPA).

Methods: 223 newly diagnosed MPA patients, with treatment initiated between 2005 and 2023 in the REVEAL cohort, were divided by 6-month glucocorticoid dose (≤10 vs >10 mg/day prednisolone-equivalent). Baseline characteristics were balanced using overlap weighting based on age, sex, disease severity, disease activity, lung/kidney involvement, initial treatment, and year of treatment initiation.

TIGIT deficiency promotes autoreactive CD4 T-cell responses through a metabolic‒epigenetic mechanism in autoimmune myositis.

Polymyositis (PM) is a systemic autoimmune disease characterized by muscular inflammatory infiltrates and degeneration. T-cell immunoreceptor with Ig and ITIM domains (TIGIT) contributes to immune tolerance by inhibiting T cell-mediated autoimmunity. Here, we show that a reduced expression of TIGIT in CD4 T cells from patients with PM promotes these cells' differentiation into Th1 and Th17 cells, which could be rescued by TIGIT overexpression.

Comparative Insights on IL-5 Targeting with Mepolizumab and Benralizumab: Enhancing EGPA Treatment Strategies.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis characterized by extravascular granulomas and eosinophilia in both blood and tissues. Eosinophils, which play a critical role in the pathophysiology of EGPA, require interleukin (IL)-5 for maturation in the bone marrow and migration to tissues. Glucocorticoids and immunosuppressants have been the cornerstone of treatment; however, their side effects have imposed a significant burden on many patients.

Ozoralizumab shows effectiveness regardless of baseline RF and ACPA titres in patients with RA: a post hoc analysis of the OHZORA trial.

Objectives: Ozoralizumab (OZR) is a next-generation anti-TNF NANOBODY® compound. The primary objective was to evaluate the efficacy of OZR in patients with RA in varying RF and anti-citrullinated peptide antibody (ACPA) titres. The secondary objective was to evaluate the changes in RF and ACPA titres following OZR treatment.

Rheumatoid Factor: Diagnostic and Prognostic Performance and Therapeutic Implications in Rheumatoid Arthritis.

Rheumatoid factor (RF) is the first autoantibody identified in rheumatoid arthritis (RA) which targets the fragment crystallizable (Fc) region of immunoglobulin (Ig) G. Although IgM isotype is predominant, other Ig isotypes, including IgG and IgA, also exist. While RF is not specific to RA, it remains a valuable serological test for diagnosing the disease, as evidenced by its inclusion in the 2010 classification criteria for RA based on elevated serum RF levels.

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.

Identification of novel clinical subtypes in patients with microscopic polyangiitis using cluster analysis: multicenter REVEAL cohort study.

Introduction: This study aimed to identify new clinical phenotypes of microscopic polyangiitis (MPA) using a principal components analysis (PCA)-based cluster analysis.

Methods: A total of 189 patients with MPA between May 2005 and December 2021 were enrolled from a multicenter cohort in Japan (REVEAL cohort). Categorical PCA and cluster analysis were performed based on clinical, laboratory, and radiological findings.

Poor prognostic factors for relapse of interstitial lung disease in microscopic polyangiitis: the Japanese multicentre REVEAL cohort study.

Background: This study investigated poor prognostic factors for the relapse of interstitial lung disease (ILD) in patients with microscopic polyangiitis (MPA) after remission induction therapy.

Methods: We enrolled patients diagnosed with MPA complicated by ILD according to the Chapel Hill Consensus definition from 2001 to 2023 in multiple institutions in the REVEAL cohort. All patients who were treated with immunosuppressive therapy were followed up, and those who relapsed with ILD were extracted in this study.

Immune Response to an Adjuvanted Recombinant Zoster Vaccine in Japanese Patients with Rheumatoid Arthritis Receiving Upadacitinib (End Zoster-J Study): Study Protocol for an Exploratory Parallel Triple-Arm Prospective Trial.

: Janus kinase (JAK) inhibitors have emerged as a new class of disease-modifying anti-rheumatic drugs in the treatment of rheumatoid arthritis (RA). However, herpes zoster is one of the common adverse events of JAK inhibitors, including upadacitinib, which is especially high in Japanese patients with RA compared to those from Western countries. Recombinant zoster vaccine (Shingrix) is an adjuvanted subunit vaccine containing varicella-zoster virus (VZV) glycoprotein E (gE) that is effective in adults over 50 years of age.

Bridging Gaps and Charting Future Directions in Vasculitis.

The field of vasculitis continues to evolve rapidly, driven by breakthroughs in both basic and clinical research [...

Long-term efficacy of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: a propensity score matching analysis in the multicenter REVEAL cohort study.

Background: Mepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in real-world settings.

Objectives: This study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023.

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.

Exploring the Link between Varicella-Zoster Virus, Autoimmune Diseases, and the Role of Recombinant Zoster Vaccine.

The varicella-zoster virus (VZV) is a human neurotropic herpes virus responsible for varicella and herpes zoster (HZ). Following primary infection in childhood, VZV manifests as varicella (chickenpox) and enters a period of latency within the dorsal root ganglion. A compromised cellular immune response due to aging or immunosuppression triggers viral reactivation and the development of HZ (shingles).

Factors associated with drug retention of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: A multicentre REVEAL cohort study.

Objectives: To determine the current retention rate of mepolizumab (MPZ) and identify factors associated with drug retention in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in the Kansai multicentre cohort (REVEAL cohort).

Methods: Sixty patients diagnosed with EGPA and treated with MPZ between December 2016 and June 2023 were enrolled. The clinical characteristics, including laboratory data, treatments administered, and disease course outcomes, were collected retrospectively.

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.

Risk factors for serious infections and infection-related mortality in patients with microscopic polyangiitis: Multicentre REVEAL cohort study.

Objective: Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes.

Methods: This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort].

Lymphoproliferative disorder progressing after partial remission following immunosuppressive drugs withdrawal in a patient with rheumatoid arthritis.

Lymphoproliferative disorders (LPDs) are serious complications that arise in patients with rheumatoid arthritis (RA) receiving immunosuppressive drugs (ISDs). Here, we reported a 73-year-old woman diagnosed with RA at 60 years of age and treated with methotrexate, bucillamine, prednisolone, and infliximab. She was referred to our hospital, Osaka Metropolitan University Hospital, with general malaise, pancytopenia, a right adrenal mass, and enlarged periaortic lymph nodes.

Identification of the VLDLR locus associated with giant cell arteritis and the possible causal role of low-density lipoprotein cholesterol in its pathogenesis.

Objectives: To elucidate the association between genetic variants and the risk of GCA via large-scale genome-wide association studies (GWAS). In addition, to assess the causal effect of a specific molecule by employing the obtained GWAS results as genetic epidemiological tools.

Methods: We applied additional variant quality control to the publicly available GWAS results from the biobanks of the UK (UKBB) and Finland (FinnGen), which comprised 532 cases vs 408 565 controls and 884 cases vs 332 115 controls, respectively.