Objectives Myositis-associated interstitial lung disease (ILD) is a potentially fatal disease, despite combination therapy with glucocorticoids (GC) and other immunosuppressive agents. New therapies, including biologics targeting relevant cytokines, such as interleukin (IL)-6, are warranted. We retrospectively reviewed patients with myositis-associated ILD who were treated with the IL-6 inhibitor tocilizumab (TCZ) to determine the clinical usefulness of TCZ.Methods Four patients with myositis-associated ILD treated with TCZ between 2019 and 2023 were identified from the records of our medical centre.Results All patients were female, aged 43–84 years. One patient was positive for the antimelanoma differentiation-associated gene 5 antibody, while the others were positive for anti-aminoacyl-tRNA synthetase antibodies. All patients met the classification criteria for rheumatoid arthritis. The initial GC dose was 1 mg/kg/day (40–60 mg/day) of prednisolone, and GC-pulse therapy was administered to all but one patient. TCZ treatment was initiated within 6 months of the initial treatment. All patients showed clinical and radiological improvements after TCZ therapy, achieving GC reduction or withdrawal. The Warrick score, which semi-quantitatively evaluates ILD, improved from a median of 14.5 (moderate) to 4 (mild). Furthermore, no relapse or serious adverse events were observed.Conclusion TCZ is a potential treatment option for refractory myositis-associated ILD.
Sjögren disease (SjD) requires ocular surface assessment during diagnostic evaluation. In Japan, the 1999 revised Japanese Ministry of Health criteria include the van Bijsterveld score based on the Rose Bengal test; however, this test is rarely performed in current clinical practice. Although fluorescein staining with the yellow filter is widely used as an alternative method, its performance for suspected SjD remains unclear. To clinically evaluate this method, this multicenter retrospective study included 400 patients who underwent fluorescein staining with the yellow filter for suspected SjD between 2010 and 2024. Expert clinical diagnosis served as the reference diagnosis, with 322 being diagnosed with SjD and 78 classified as non-SjD. At a cutoff value ≥3 for the van Bijsterveld score using fluorescein staining with the yellow filter, sensitivity was 48.4% and specificity 84.6%, with a positive predictive value of 92.9%. At a cutoff value ≥4, sensitivity was 32.6% and specificity 93.6%, with a positive predictive value of 95.5%. After replacing the Rose Bengal test in the 1999 criteria with fluorescein staining with the yellow filter, the modified criteria showed 86.6% sensitivity, 93.6% specificity, and 88.0% accuracy. Fluorescein staining with the yellow filter may be a practical ocular assessment method for suspected SjD.
Reduced gut microbial diversity is associated with adverse outcomes in hematological malignancies. However, longitudinal studies during lymphoma chemoimmunotherapy rarely distinguish richness from evenness. We investigated whether microbial diversity shifts during anti-CD20-containing chemoimmunotherapy reflect loss of detected taxa or redistribution of relative abundances. In this prospective, single-center exploratory study, 40 patients with B-cell lymphoma provided pretreatment stool samples and 18 paired post-treatment samples. All 18 participants received trimethoprim–sulfamethoxazole (TMP-SMX) prophylaxis from treatment initiation through post-treatment sampling, without additional systemic antibacterial exposure between collections or during the 3 months preceding baseline. Following 16S rRNA gene V3–V4 sequencing, Pielou’s evenness (q = 0.0077) and Shannon diversity (q = 0.0208) decreased post-treatment, whereas observed features and Faith’s phylogenetic diversity did not change significantly (q = 0.4923 and 0.7660, respectively). Dominance significantly increased (Simpson, q = 0.0154; Berger–Parker, q = 0.0237). Beta diversity showed no detectable compositional shift, no genus-level taxon met differential-abundance criteria, and newly dominant taxa varied across individuals. These changes accompanied the combined treatment exposure in a cohort that may overrepresent clinically stable patients; the chemoimmunotherapy and TMP-SMX contributions were inseparable. These alterations appear modest and predominantly structural, with the clearest changes in evenness and dominance, and substantial uncertainty about richness.
Rheumatoid arthritis (RA) is characterized by chronic inflammatory polyarthritis. Despite recent advances in treatment, a subset of patients remains refractory, highlighting the need for better biomarkers for diagnosis and disease activity monitoring to determine appropriate interventions. Therefore, this study aimed to characterize the plasma metabolic profiles of RA and identify candidate metabolite markers for the disease. Plasma samples from treatment-naïve patients with newly diagnosed RA (n = 48) and healthy controls (HC; n = 45) were analyzed using liquid chromatography-tandem mass spectrometry. Fifty-five metabolites were included in the analysis; carnosine, glutamic acid, dimethylglycine, and taurine were significantly increased in RA, whereas histidine, methionine sulfoxide, tryptophan, and alanine were significantly decreased. Metabolite set enrichment analysis showed altered histidine metabolism in patients with RA, and the carnosine/histidine ratio showed the highest area under the ROC curve among the metabolites tested. Histidine was also inversely associated with disease activity and anti-citrullinated protein antibody (ACPA) production. In addition, decreased citrulline levels were significantly associated with higher ACPA production. This study identified the carnosine/histidine ratio as a candidate marker for RA and implicates an imbalance between carnosine synthesis and degradation in its pathophysiology, based on an analysis of treatment-naïve patients with covariate adjustments.
Juvenile dermatomyositis (JDM) is an autoimmune myopathy with skin manifestations, yet biomarkers reflecting disease activity and organ involvement at presentation remain incompletely defined. This study aimed to identify clinical and immunologic indicators at diagnosis, focusing on myositis-specific autoantibodies (MSAs) and lymphocyte subsets. We retrospectively analyzed 36 patients with JDM treated at a tertiary center in Japan between 2003 and 2024. MSAs (anti-TIF1-γ, anti-MDA5, anti-NXP2, anti-Mi-2, anti-Jo-1, anti-ARS, and anti-SAE) were assessed at diagnosis. Clinical features, laboratory data, and lymphocyte profiles by flow cytometry were compared across MSA subtypes. The cohort (25 females) showed a bimodal age distribution with peaks at 4 and 10 years. Anti-Jo-1 and anti-TIF1-γ antibodies predominated in younger patients, whereas anti-NXP2 was more frequent in older children. Patients with ILD had higher anti-MDA5 positivity (adjusted p = 0.005) and KL-6 levels (adjusted p = 0.007). Both absolute and age-normalized CD8+ T-cell levels were higher in patients with subcutaneous calcinosis (adjusted p = 0.012 for both). Age-dependent MSA profiles characterize JDM. Anti-MDA5 antibodies were associated with ILD, whereas higher age-normalized CD8+ T-cell levels were associated with calcinosis, suggesting their potential utility for risk stratification at diagnosis.
