Ozoralizumab（OZR）, a novel tumor necrosis factor（TNF）inhibitor, is a low molecular weight antibody approved in Japan for the treatment of rheumatoid arthritis（RA）inadequately managed by currently available treatments. OZR has a distinctive trimeric structure consisting of 2 anti-TNFα NANOBODY^® molecules and 1 anti-human serum albumin NANOBODY^® molecule, without a fragment crystallizable（Fc）region. Its long half-life allows subcutaneous injection once every 4 weeks. Prior clinical studies conducted in Japan have shown the efficacy of OZR in RA inadequately managed by currently available treatments, regardless of concurrent methotrexate use. OZR can rapidly distribute to inflamed sites and provide rapid-onset anti-inflammatory effects when subcutaneously injected in mice with collagen-induced arthritis, which may potentially improve treatment adherence in real-world settings. With safety comparable to existing TNF inhibitors and relatively low cellular toxicity, OZR offers a treatment option for patients with RA who have discontinued currently available treatments due to intolerance. We here present the cases treated with OZR in our institution. Further real-world studies are necessary to evaluate its safety in older patients and to assess the possibility of extending dosing intervals or achieving biologic-free remission.

Kawasaki disease（KD）is a systemic vasculitis most frequently affecting medium-sized arteries. KD is thought to develop in genetically predisposed children through activation of the innate immune system by infectious agents. Histopathologically, vascular inflammation begins with edematous changes in the media and inflammatory cell infiltration into the intima and adventitia, ultimately involving the entire vessel wall. The infiltrating cells are predominantly macrophages and neutrophils. Importantly, macrophage-predominant infiltrates are not confined to blood vessels but are also distributed within the connective tissues of various organs, including the myocardium, epicardium, cardiac valves, skin, and lymph nodes, where they produce marked edematous and exudative inflammation. These pathological features may reflect the underlying pathogenesis of KD.

Systemic vasculitis is a heterogeneous group of autoimmune and autoinflammatory disorders that target the vessel wall. Recent advances in immunology have provided novel insights into their pathogenesis. In this review, we summarize key updates in the last decade. In anti-neutrophil cytoplasmic antibody（ANCA）-associated vasculitis（AAV）, the complement C5a–C5aR axis is recognized for its role in amplifying inflammation, and the C5aR antagonist avacopan has been identified as a therapeutic option. Myeloperoxidase（MPO）-ANCA-positive interstitial lung disease（ILD）has been recognized as a distinct subset with poor prognosis, as confirmed by recent large-scale Japanese cohorts. In eosinophilic granulomatosis with polyangiitis（EGPA）, type 2 inflammation driven by IL-5 has been clarified as a central mechanism, and anti–IL-5 therapies such as mepolizumab have been introduced into clinical practice. In large-vessel vasculitis, dendritic cell–T cell interactions and reduced PD-L1 expression contribute to the breakdown of immune regulation, providing potential therapeutic targets beyond IL-6 blockade. Furthermore, newly described entities such as VEXAS syndrome, caused by somatic mutations in UBA1, and immune checkpoint inhibitor（ICI）-related vasculitis highlight the roles of somatic mutation and immune modulation in vasculitis pathogenesis. Collectively, these discoveries expand the conceptual framework of vasculitis and underscore the importance of precision medicine approaches and novel molecular targeted therapies for patient management.

Neutrophils have long been considered a homogeneous population of immune cells. However, recent studies have revealed the existence of diverse subsets distinguished by differences in maturation status and surface marker expression. Among these, low-density granulocytes（LDGs）are notably increased in various pathological conditions, including autoimmune diseases, infections, and cancer. LDGs exhibit distinct functions depending on the disease context, such as promoting inflammation or exerting immunosuppressive effects.

Neutrophil extracellular traps（NETs）, web-like structures composed of DNA and antimicrobial proteins released by activated neutrophils, contribute to pathogen elimination as part of the innate immune response. However, excessive NET formation or impaired degradation can lead to tissue damage, thrombosis, and the induction of autoantibody production. In autoimmune diseases such as ANCA-associated vasculitis, IgA vasculitis, and systemic lupus erythematosus, NETs play a central role in disease pathogenesis.

This review provides an overview of the functional diversity of neutrophils and the pathological significance of NETs, with a particular focus on their involvement in autoimmune diseases.

Various animal models of anti-neutrophil cytoplasmic antibody（ANCA）-associated vasculitis（AAV）, including passive and active immunization models as well as spontaneous models, have been developed to investigate the pathogenicity of ANCA and disease mechanisms, and to evaluate novel therapeutic candidates. Passive immunization models allow for direct investigation of neutrophil activation and tissue injury induced by ANCA, while active immunization models enable the study of the immune response induction process against autoantigens. Advances in both basic research using animal models and clinical studies have significantly deepened our understanding of AAV pathogenesis. In particular, recent insights into neutrophil priming and the molecular mechanisms underlying neutrophil extracellular trap formation have led to the identification of new therapeutic targets. Molecular targeted therapies directed against B cells, T cells, complement components, and neutrophil activation pathways are currently under development, with several agents in preclinical or clinical trial stages. Moving forward, treatment strategies tailored to disease phase and improved accuracy in predicting relapse will be essential. Integration of basic and clinical research will play a key role in optimizing individualized therapeutic approaches for patients with AAV.

［Objectives］

We reviewed unidentified arthritis（UA）from the diagnosis to one year later.

［Methods］

In patients who had arthritis and consulted our institute, where the baseline（BL）was defined and they were followed up for at least one year from August 2010 to July 2023, undefined arthritis— which is characterized as having an onset of less than six months and scoring fewer than six points in the ACR/EULAR classification criteria（CC）for rheumatoid arthritis（RA） —was identified. Their diagnosis, CC score, number of RA cases, simplified disease activity index（SDAI）score, and the number of flares, defined as an SDAI score elevated by no less than 5.7, along with methotrexate（MTX）dosage at BL within one year, were reviewed.

［Results］

A total of 115 patients matched the inclusion criteria. At one year, the diagnoses were 24 UAs, 63 RAs, 12 psoriatic arthritis, four ankylosing spondylitis（AS）, and 12 others. Only RA-diagnosed patients fulfilled the CC of RA. MTX was administered to all the patients. The mean MTX dosage was 7.8mg per week for the RA patients and 6 to 8 mg for the other patients. The mean SDAI at BL was 10.4 in RA, 8.8 in UA, 8.3 in PsA, 9.5 in AS, and 4.7 to 13.3 in others. The flare was marked in two RA patients.

［Conclusions］

It seems effective in administering MTX at BL for the UA patients to prevent flare. After the UA diagnosis, a flexible response is needed, not to be obsessed with the initial diagnosis.

【Objectives】

We investigated whether daily folic acid administration was effective in reducing side effects in rheumatoid arthritis（RA）patients using methotrexate（MTX）and whether it affected disease activity in RA patients.

【Methods】

Of 81 MTX-treated RA patients who received daily folic acid（1mg）, we analyzed 66 patients and investigated their adverse effects. We excluded seven patients who were prescribed folic acid continuously from other hospitals and eight patients who had no history of folic acid administration. Eleven MTX-treated RA patients who had no change in treatment other than the change from weekly folic acid（5mg）to daily folic acid（1mg）, were followed up for 6 months, and DAS-28, ESR, SDAI, ESR, CRP, AST, ALT, WBC, PLT, and other side effects were evaluated.

【Results】

The analysis of 66 patients showed that gastrointestinal symptoms significantly improved, and fatigue also showed a trend toward improvement. The analysis of 11 patients who changed from weekly folic acid（5mg）to daily folic acid（1mg）showed no significant differences in DAS-28（ESR）, SDAI, ESR, CRP, ALT, WBC, or PLT. The AST level showed significant improvement. With regard to other side effects, gastrointestinal symptoms showed a trend toward improvement.

【Conclusion】

In an analysis of 66 patients, the daily administration of folic acid reduced adverse effects. Although this was a small number of cases, the analysis of 11 patients showed that the daily administration of folic acid may not worsen disease activity.

  The exacerbation of hip osteoarthritis（hip OA）is directly linked to a significant decline in patientsʼ activities of daily living and 1uality of life in Japan, a nation with a super-aging society. As the number of individuals affected by hip OA is expected to continuously increase, there is a pressing need to establish and implement Disease-Modifying Osteoarthritis Drugs（DMOADs）. These novel therapies could potentially reduce the number of patients who ultimately require surgical intervention.

  However, clinical trials for DMOADs have predominantly focused on the knee joint, with limited research currently available for the hip. A wide range of potential DMOADs with various mechanisms of action are under investigation. These candidates include: Enzyme inhibitors, such as MMP and ADAMTS inhibitors, Wnt signaling pathway suppressors, like lorecivivint and verapamil, Cartilage repair promoters, such as LNA043, sprifermin, and kartogenin, Inflammation suppressors, like metformin, TPCA-1, and tofacitinib, Inhibitors of abnormal subchondral bone remodeling, for instance, zoledronic acid and MIV-711.

  This symposium aims to provide an overview of the current status and challenges in the development of DMOADs and platelet-rich plasma therapy for osteoarthritis, with a particular focus on the hip joint.