Discovery of ETI41 and ETI60: novel selective endosomal Toll-like receptor inhibitors for the treatment of autoimmune diseases.

Endosomal Toll-like receptors (TLRs, including TLR3, TLR7, TLR8 and TLR9) play crucial roles in immune responses by recognizing pathogen-associated molecular patterns; however, their aberrant activation is implicated in inflammatory and autoimmune diseases. Developing endosomal TLR inhibitors against autoimmune diseases is clinically essential. Here we synthesized and optimized a series of compounds based on a candidate structure.

Comprehensive analysis of patients with rheumatoid arthritis associated interstitial lung disease.

Background/aims: To investigate the demographics, disease characteristics, and treatment modalities of patients with rheumatoid arthritis (RA) associated interstitial lung disease (ILD), focusing on ILD exacerbation and mortality.

Methods: This retrospective study included individuals aged ≥ 18 years diagnosed with RA-ILD at Ajou University Hospital from January 1999 to March 2022. Diagnosis was based on chest computed tomography (CT) scans; progression was monitored based on available follow-up pulmonary function tests (PFTs) and chest CTs.

Efficacy and safety of epaminurad, a potent hURAT1 inhibitor, in patients with gout: a randomized, placebo-controlled, dose-finding study.

Background: Gout is the most common inflammatory arthritis. Current urate-lowering therapies have limitations, such as adverse drug reactions or limited efficacy. Epaminurad is a novel selective human urate transporter 1 (hURAT1) inhibitor that has been shown to reduce serum urate (sUA) levels in healthy volunteers and patients with gout.

Difficult-to-treat rheumatoid arthritis among elderly patients from the KOBIO registry.

Background: 'Difficult-to-treat (D2T)' rheumatoid arthritis (RA) refers to patients who fail to achieve low disease activity or remission despite multiple biologic or targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARD) cycles. Elderly RA patients often have higher disease activity and more comorbidities. This study aimed to determine the prevalence of D2T-RA in elderly RA patients treated with b/tsDMARDs and examine their characteristics and treatment outcomes.

Characterising infusion/injection-related reactions in patients with rheumatoid arthritis treated with biologic agents.

Objectives: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) have transformed the management of rheumatoid arthritis (RA), but their efficacy can be limited by infusion/injection-related reactions (IRRs). This study investigated demographic and clinical factors associated with IRRs in patients with RA using data from the Korean College of Rheumatology Biologics & Targeted Therapy (KOBIO) Registry.

Methods: We analysed 1,832 patients with RA, categorising them into IRR and non-IRR groups.

Evaluation of Inflammatory Scores as Diagnostic Markers for Polymyalgia Rheumatica.

Objective: Polymyalgia rheumatica (PMR) is a chronic inflammatory rheumatic disease affecting older adults, with symptoms often overlapping with those of other conditions, thus making its diagnosis challenging. The present study evaluated the utility of laboratory-based inflammatory scores, including the systemic immune-inflammation index (SII), C-reactive protein-to-albumin ratio (CAR), albumin-to-globulin ratio (AGR), and prognostic nutritional index (PNI), as diagnostic tools for PMR and explored their association with clinical manifestations.

Methods: This retrospective study analyzed the medical records of 156 patients diagnosed with PMR and 408 diagnosed with rheumatoid arthritis (RA) between 2001 and 2021 to evaluate the diagnostic performance of inflammatory scores in distinguishing between the two conditions.

Impact of disease-related indicators on pain measures in rheumatoid arthritis: a biopsychosocial perspective.

Objective: Pain is a significant and debilitating symptom of rheumatoid arthritis (RA) that significantly affects the quality of life and functional ability of patients. In the present study, we examined the association between pain variables and disease activity markers in patients with RA.

Methods: We enrolled 133 patients with RA and assessed their clinical characteristics, socioeconomic and psychological factors, and pain measures.

mHealth-Based Self-Management Program for Patients With Rheumatoid Arthritis: A Pilot Randomized Controlled Study.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that gradually limits physical function and decreases quality of life (QOL). We evaluated an mHealth-based self-management program to help patients with RA improve their physical and psychological health, self-efficacy, physical activity, and QOL. The sample included 73 experimental and 69 control participants.

Anti-TCP1 Antibody Is a Potential Biomarker for Diagnosing Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease caused by autoantibodies. Serum samples from patients with SLE ( = 10) were compared with those from normal controls (NCs, = 5) using 21K protein chip analysis to identify a biomarker for SLE, revealing 63 SLE-specific autoantibodies. The anti-chaperonin-containing t-complex polypeptide-1 (TCP1) antibody exhibited higher expression in patients with SLE than in NCs.

Inhibition of Toll-like Receptors Alters Macrophage Cholesterol Efflux and Foam Cell Formation.

Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages.

Longitudinal assessment of urinary ALCAM, HPX, and PRDX6 in Korean patients with systemic lupus erythematosus: implications for disease activity monitoring and treatment response.

Introduction: This study aimed to demonstrate the potential of activated leukocyte cell adhesion molecule (ALCAM), hemopexin (HPX), and peroxiredoxin 6 (PRDX6) as urine biomarkers for systemic lupus erythematosus (SLE).

Methods: Urine samples were collected from 138 Korean patients with SLE from the Ajou Lupus Cohort and 39 healthy controls (HC). The concentrations of urine biomarkers were analyzed using enzyme-linked immunosorbent assay kits specific for ALCAM, HPX, and PRDX6, respectively.

Role of chemokines CXCL9, CXCL10, CXCL11, and CXCR3 in the serum and minor salivary gland tissues of patients with Sjögren's syndrome.

This study aimed to investigate the serum and expression levels of C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, CXCL11, and CXC receptor 3 (CXCR3) in minor salivary glands (MSGs) of patients with primary Sjögren's syndrome (pSS), and to explore their correlations with clinical parameters. Serum samples from 49 patients diagnosed with pSS, 33 patients with rheumatoid arthritis (RA), and 30 healthy controls (HCs) were collected for measurements of CXCL9, CXCL10, CXCL11, and CXCR3. Additionally, CXCL levels in the MSG tissues were measured in 41 patients who underwent MSG biopsy.

Uncovering risk factors for adverse events and infections in rheumatoid arthritis and rheumatoid arthritis with interstitial lung disease under treatment with biologics or targeted synthetic DMARDs: insights from the KOBIO Registry.

Objectives: This study aimed to identify the risk factors associated with overall adverse events (AEs) and infections in patients with rheumatoid arthritis (RA) and comorbid interstitial lung disease (ILD), receiving biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs), using data from the Korean College of Rheumatology Biologics registry.

Methods: We analysed data from a cohort of 2,266 adult patients with RA who received b/tsDMARDs, including 169 patients with comorbid ILD. We identified the risk factors for overall AEs and infections in both the all RA group and the subgroup of patients with RA-ILD and investigated the impact of infections on mortality in patients with RA-ILD.

Patient preference, efficacy, and compliance with zoledronic acid for glucocorticoid-induced osteoporosis in patients with autoimmune diseases.

Purpose: We evaluated the preference, patient satisfaction, and efficacy of zoledronic acid compared with oral bisphosphonates (BPs) for glucocorticoid-induced osteoporosis (GIOP) in patients with autoimmune diseases.

Methods: We enrolled 50 patients with new fractures or osteoporosis detected on follow-up bone densitometry after at least 1 year of oral BP use among patients diagnosed with GIOP during treatment for autoimmune diseases. After 1 year of zoledronic acid treatment, patients completed a survey for preference and satisfaction assessment.

Clinical characteristics and prognostic factors of non-tuberculous mycobacterial disease in patients with rheumatoid arthritis.

Background/aims: This study aimed to identify the clinical characteristics of patients with concurrent rheumatoid arthritis (RA) and suspected non-tuberculous mycobacterial (NTM) infections as well as determine their prognostic factors.

Methods: We retrospectively reviewed the medical records of 91 patients with RA whose computed tomography (CT) findings suggested NTM infection. Subsequently, we compared the clinical characteristics between patients with and without clinical or radiological exacerbation of NTM-pulmonary disease (PD) and investigated the risk factors for the exacerbation and associated mortality.

Biosimilars in the treatment of rheumatoid arthritis: a pharmacokinetic overview.

Introduction: As of May 2023, 19 and 18 biosimilars have been approved for the treatment of rheumatoid arthritis (RA) by the European Medicines Agency (EMA) and United States Food and Drug Administration (US FDA) respectively.

Area Covered: Pharmacokinetic results of phase 1 studies of approved biosimilars were reviewed by systematic literature search. The impact of immunogenicity on the pharmacokinetic data and clinical response was assessed, and the potential benefit of monitoring serum concentrations of biologic drugs is discussed.

Effects of COVID-19 and Influenza Vaccination on Rheumatic Diseases: Results From a Survey of Patient-Reported Outcomes After Vaccination.

Background: This study aimed to compare the occurrence of adverse events (AEs) and disease flares after vaccination against coronavirus disease 2019 (COVID-19) and influenza in patients with autoimmune rheumatic diseases (ARDs).

Methods: Between November 2021 and March 2022, a survey was conducted among patients with ARD who received COVID-19 and influenza vaccinations. The questionnaire included 11 mandatory and closed-ended questions, and the following items were collected: medical history, immunization history, type of vaccine, patient-reported AEs, flare-up of the underlying disease after vaccination, and a confirmed diagnosis of COVID-19 or influenza.

Association between CCR2 and CCL2 expression and NET stimulation in adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by the activation of monocyte-derived cells and the release of neutrophil extracellular traps (NET). C-C motif ligand (CCL) 2 is a chemoattractant that interacts with the C-C motif chemokine receptor (CCR) 2, resulting in monocyte recruitment and activation. CCL2 and CCR2 were measured with enzyme-linked immunosorbent assay (ELISA) at the serum level, and using immunohistochemical staining at the skin and lymph node tissues levels.

Rosuvastatin treatment alone cannot alleviate lupus in murine model: a pilot study.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by the production of autoantibodies and high cholesterol levels. HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors have exhibited anti-inflammatory effects in several clinical trials. We conducted this study to evaluate the effect of rosuvastatin on inflammatory responses in lupus-prone mice.

The transcription factor Mef2d regulates B:T synapse-dependent GC-T differentiation and IL-21-mediated humoral immunity.

Communication between CD4 T cells and cognate B cells is key for the former to fully mature into germinal center-T follicular helper (GC-T) cells and for the latter to mount a CD4 T cell-dependent humoral immune response. Although this interaction occurs in a B:T synapse-dependent manner, how CD4 T cells transcriptionally regulate B:T synapse formation remains largely unknown. Here, we report that Mef2d, an isoform of the myocyte enhancer factor 2 (Mef2) transcription factor family, is a critical regulator of this process.