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. RF is also associated with RA severity, including joint damage and extra-articular manifestations, serving as a poor prognostic factor and aiding in the identification of difficult-to-treat RA. Recent studies have demonstrated that high serum RF levels are associated with a reduced response to tumor necrosis factor (TNF) inhibitors. In contrast, anti-TNF antibodies lacking the Fc portion have shown stable efficacy in RA patients regardless of baseline RF levels. These findings reaffirm the clinical significance of RF measurement, 80 years after its initial discovery. This review explores the diagnostic and prognostic significance of RF and its impact on treatment selection in RA management.

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). Patients with autoimmune diseases have a higher risk of developing HZ owing to the immunodeficiency associated with the disease itself and/or the use of immunosuppressive agents. The introduction of new immunosuppressive agents with unique mechanisms has expanded the treatment options for autoimmune diseases but has also increased the risk of HZ. Specifically, Janus kinase (JAK) inhibitors and anifrolumab have raised concerns regarding HZ. Despite treatment advances, a substantial number of patients suffer from complications such as postherpetic neuralgia for prolonged periods. The adjuvanted recombinant zoster vaccine (RZV) is considered safe and effective even in immunocompromised patients. The widespread adoption of RZV may reduce the health and socioeconomic burdens of HZ patients. This review covers the link between VZV and autoimmune diseases, assesses the risk of HZ associated with immunosuppressant use, and discusses the benefits and risks of using RZV in patients with autoimmune diseases.

Type I interferons (IFN-I) are pivotal effectors of innate immunity and constitute a central axis of host defense against pathogens. Sensing of exogenous or endogenous nucleic acids by pattern-recognition receptors—exemplified by Toll-like receptors—triggers transcriptional induction of IFN-I. Engagement of the heterodimeric IFN-I receptor on nucleated cells reprograms cellular states via canonical Janus kinase–signal transducer and activator of transcription (JAK–STAT) signaling as well as STAT-independent, noncanonical pathways. This axis is tempered by multilayered regulatory mechanisms, including epigenetic remodeling, and important aspects remain incompletely defined. Dysregulation of IFN-I activity underlies diverse autoimmune disorders, notably systemic lupus erythematosus, wherein IFN-responsive gene signatures stratify disease endotypes, reflect disease activity trajectories, and predict therapeutic responsiveness. In recent years, therapeutic strategies targeting this pathway are now available: anti-IFN-I receptor therapy for systemic lupus erythematosus (SLE) and JAK inhibition for rheumatoid arthritis (RA) and giant cell arteritis (GCA). Altogether, a refined understanding of the IFN-I axis furnishes a pragmatic framework for patient stratification, response prediction, and mechanism-informed therapy design across immune-mediated diseases.

Objective: This study aimed to compare drug retention rates according to the baseline neutrophil-to-lymphocyte ratio (NLR) in patients with RA initiating biologic/targeted synthetic DMARDs (b/tsDMARDs). Methods: Data were obtained from 774 treatment courses with moderate to high disease activity at the initiation of b/tsDMARD therapy from the Kansai Multicentre ANSWER cohort. Patients were categorized into NLRlow group and NLRhigh group based on the median NLR value of 3.30. A multivariate Cox proportional hazards model, adjusted for potential confounders, was used to estimate hazard ratios (HRs) for drug retention over 2 years. Results: Patients in the NLRhigh group exhibited significantly higher baseline Clinical Disease Activity Index (CDAI) scores (P = 0.004) and more frequent glucocorticoid use (P < 0.001) than those in the NLRlow group. In the NLRlow group, drug retention rates did not significantly differ among tumour necrosis factor inhibitors (TNFi), anti-IL-6 receptor antibodies (aIL-6R), cytotoxic T lymphocyte antigen 4 immunoglobulin (CTLA4-Ig) and Janus kinase inhibitors (JAKi). In contrast, within the NLRhigh group, treatment with aIL-6R and JAKi was associated with significantly higher retention rates compared with TNFi (HR = 0.53, 95% CI: 0.32–0.88; HR = 0.36, 95% CI: 0.20–0.64, respectively). At 12 months, CDAI scores did not significantly differ among the four treatment groups in either NLR group. Conclusion: In patients with elevated baseline NLR values, aIL-6R and JAKi may offer superior drug retention compared with TNFi when initiating b/tsDMARD therapy.

Rheumatoid arthritis (RA) has traditionally been managed after the onset of clinically apparent synovitis; however, accumulating evidence indicates that disease-related immune abnormalities precede clinical diagnosis by several years. This preclinical phase is characterized by systemic autoimmunity, early musculoskeletal symptoms, and subclinical inflammation in genetically and environmentally susceptible individuals. In this review, we summarize current concepts regarding the pathogenesis, risk stratification, and therapeutic interception of preclinical RA. Particular attention is given to the mucosal origin hypothesis and to the roles of immunosenescence, peripheral helper T cells, and fibroblast-like synoviocytes in early disease evolution. Recent advances in clinical, serological, and imaging-based risk stratification have improved the identification of individuals at high risk of progression to clinical RA, and emerging intervention trials have shown that selected therapies may delay disease onset or reduce early inflammatory burden. Although complete prevention of RA has not yet been achieved, these findings support a paradigm shift from the treatment of established RA toward earlier, risk-adapted intervention before irreversible joint damage occurs. Future efforts should focus on refining predictive biomarkers, optimizing the timing and intensity of intervention, and establishing safe, individualized preventive strategies.

Objectives: To compare early changes in RF across classes of biological or targeted synthetic DMARDs (b/tsDMARDs) and assess whether early RF decline was associated with 12-month clinical remission in RA. Methods: We retrospectively analysed 1423 newly initiated b/tsDMARD treatment courses from the multicentre ANSWER cohort that continued for ≥12 months and had RF measured at baseline and 3 months. Early RF decline was defined as a ≥20% reduction at 3 months. Multivariable regression assessed factors associated with RF change and 12-month Clinical Disease Activity Index (CDAI) remission. Twelve-month remission rates were also compared across four categories of RF reduction. Results: RF reduction differed across classes, with Janus kinase inhibitors (JAKi) showing the greatest decline. Compared with TNF inhibitors (TNFi), JAKi were associated with a greater RF reduction (β = −14.50, 95% CI: −20.04 to −8.97; P < 0.001). The direction was similar in multiple sensitivity analyses and remained significant in propensity score–matched analyses. Early RF decline was independently associated with 12-month CDAI remission (adjusted OR 1.39, 95% CI: 1.04–1.88; P = 0.029). A significant overall trend towards higher 12-month remission rates was observed across categories of greater RF reduction (P for trend = 0.004). Conclusion: Early RF decline differed across b/tsDMARD classes and was associated with 12-month remission. Longitudinal RF dynamics may provide clinically useful prognostic information in RA.