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The advent of biologics has greatly improved patient outcomes, yet some patients are compelled to switch therapies. Predicting these therapeutic failures is important; however, the factors associated with switching biologics have not been fully explored. This study examined patterns and determinants of biologics switching in psoriasis treatment retrospectively over 13 years. We focused on the association between clinical characteristics, basal laboratory data, and frequency of biologics switching. The findings revealed that elevated Psoriasis Area Severity Index scores and the presence of arthritis were observed in patients who experienced two or more treatment switches compared with those without treatment switches. Moreover, neutrophil to lymphocyte ratio was associated with higher biologics switching rates, indicating that systemic inflammation significantly impacts treatment adherence. A treatment approach, taking into account both the clinical presentation and inflammatory biomarkers, may be important for optimizing patient management in psoriasis. [ABSTRACT FROM AUTHOR]

Objectives PsA is one of the most serious comorbidities associated with psoriasis. While the early intervention in PsA is demanded, risk factors of PsA development are not well-known. This is the first prospective study to evaluate the clinical significance of nailfold capillary (NFC) changes in patients with psoriasis. Methods We conducted a prospective cohort study in a population of 449 psoriasis patients who had not been treated with systemic therapy or topical finger therapy. NFCs were observed by dermoscopy and capillaroscopy, and the correlation of NFC abnormalities, including nailfold bleeding (NFB) and enlarged capillaries, with the prevalence of PsA, incidence of new PsA, and serum levels of TNF-a, IL-17A and IL-23 were analysed. Results Detailed examination at the time of inclusion revealed that of 449 patients, 236 had Psoriasis vulgaris (PsV) and 213 had PsA. Both NFB and enlarged capillaries were significantly more frequent in patients with PsA (34.7% vs 84.5%, P  < 0.0001; 25.4% vs 100%, P  < 0.0001). In addition, PsV patients were prospectively observed before they developed PsA (mean 21 months, 95% CI 2, 77 months). Multivariate analysis suggested that the appearance of NFB and enlarged capillaries was a predictor of PsA development (HR 2.75, 95% CI 1.38, 5.47 and HR 4.49, 95% CI 2.25, 8.96, respectively). The degree of NFC abnormalities also correlated with the severity of PsA and serum cytokine levels. Conclusions NFC abnormalities were suggested to be a predictor of PsA in psoriasis patients, and at the same time, its degree could be an indicator of disease severity. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple immune cell subsets. We analyzed immune cell subsets in human peripheral blood mononuclear cells (PBMC) in order to identify the cells that are significantly associated with SLE disease activity and treatment. The frequencies of various subsets of CD4+ T cells, B cells, monocytes and NK cells in PBMC were assessed in 30 healthy controls (HC), 30 rheumatoid arthritis (RA) patients and 26 SLE patients using flow cytometry. The correlations between subset frequencies in SLE and clinical traits including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were examined. Changes in subset frequencies after the treatment in SLE patients were investigated. We focused on CD25+LAG3+ T cells and investigated their characteristics, including cytokine secretion, mRNA expression and suppression capacity. We assessed correlations between CD25+LAG3+ T cells and SLEDAI by Spearman's rank correlation coefficient. CD25+LAG3+ T cells were significantly increased in SLE whereas there were few in RA and HC groups. CD25+LAG3+ T cell frequencies were significantly correlated with SLEDAI and were increased in patients with a high SLEDAI score (> 10). CD25+LAG3+ T cells produced both IL-17 and FOXP3, expressed mRNA of both FOXP3 and RORC and lacked suppressive capacity. CD25+LAG3+ T cells were associated with disease activity of SLE. CD25+LAG3+ T cells had features of both CD25+FOXP3+ regulatory T cells (CD25+ Treg) and Th17. CD25+LAG3+ T cells could be associated with the inflammatory pathophysiology of SLE. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is associated with the infiltration of IgG4-positive plasma cells into various organs. Nephropathy of IgG4-RD is generally interstitial nephritis and glomerulonephritis is rare. We describe a case of membranous nephropathy (MN) without interstitial nephritis associated with IgG4-RD symptoms including lymphadenopathy and pulmonary and pleural lesions. Treatment with steroids improved these clinical symptoms, but withdrawal of steroids induced the repeated relapse of MN. Finally, flaring of MN was prevented by the combination of steroids and cyclosporine. This is the first report of the successful treatment of MN associated with IgG4-RD by this combination therapy. [ABSTRACT FROM PUBLISHER]

Abstract: CD25+CD4+ regulatory T cells suppress immune responses and are believed to play roles in preventing autoimmune diseases. However, the mechanism(s) underlying the suppression and the regulation of their homeostasis remain to be elucidated. Here we show that these regulatory T cells downregulated CD25−CD4+ T-cell-mediated production of IL-12 from antigen-presenting cells, which can act as a growth factor for CD25−CD4+ T cells. We further found that CD25+CD4+ T cells, despite their well-documented “anergic” nature, proliferate significantly in vitro only when CD25−CD4+ T cells are present. Notably, this proliferation was strongly dependent on IL-2 and relatively independent of IL-12. Thus, CD25+CD4+ T cells suppress CD25−CD4+ T-cell responses, at least in part, by inhibiting IL-12 production while they themselves can undergo proliferation with the mediation of CD25−CD4+ T cells in vitro. These results offer a novel negative feedback system involving a tripartite interaction among CD25+CD4+ and CD25−CD4+ T cells, and APCs that may contribute to the termination of immune responses. [Copyright &y& Elsevier]

Introduction: Since the first report of a novel coronavirus infection caused by SARS-CoV-2 in late 2019, the infection has spread rapidly and had a significant impact on our lives. In the early stages of the COVID-19 pandemic, there was no adequate testing system in place, despite an urgent need for infection control measures in student dormitories., Methods: We have been monitoring SARS-CoV-2 in wastewater as part of our infection control efforts in the university facilities since fall 2020. In the four dormitories, absorbent cotton was placed in the drains that the facility wastewater passed through, and samples were collected twice a week and processed by RT-PCR for SARS-CoV-2. The dormitory residents were informed of the monitoring results the next morning., Results: The positivity of residents in the dormitories was highly consistent with the positivity of wastewater. Wastewater was positive in 89 % of cases before any residents were tested and found positive. Facility wastewater monitoring showed sensitivities of 80.4 % and specificities of 87.6 %. No traceable resident-to-resident transmission of infection within the facility was confirmed during the study period., Conclusion: Sampling a single wastewater outlet in a building for SARS-CoV-2 PCR can effectively indicate the presence or absence of COVID-19 cases and be very useful for infection control of a facility. This simple and effective monitoring is applicable to future outbreaks of both emerging and re-emerging infectious diseases., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: Interstitial lung disease sometimes occurs in rheumatoid arthritis patients. Although the underlying immunological mechanisms responsible for interstitial lung disease associated with rheumatoid arthritis have not yet been clarified, some reports have suggested possible roles of B cells. To examine the role of B-cell subsets in interstitial lung disease in rheumatoid arthritis patients, we analyzed peripheral blood B-cell subsets., Methods: We analyzed the frequencies of the peripheral blood B-cell subsets by flow cytometry in rheumatoid arthritis patients with and without interstitial lung disease ( n  = 16 and 81, respectively) and in healthy donors ( n  = 110) by high-resolution computed tomography., Results: Compared with healthy donors, rheumatoid arthritis patients showed statistically higher frequencies of naive B cells and lower frequencies of memory B cells. Moreover, the frequencies of memory B cells were lower in rheumatoid arthritis patients with interstitial lung disease than in those without. Multivariate analysis showed that the frequency of memory B cells, particularly switched memory B cells, was significantly decreased in rheumatoid arthritis patients with interstitial lung disease, even after adjusting for prednisolone dose., Conclusions: We suspect memory B cells play important roles in interstitial lung disease associated with rheumatoid arthritis.

Objectives: Glucocorticoids (GCs) are effective treatments for rheumatoid arthritis (RA) but long-term use has adverse effects. This study aimed to elucidate whether GCs can be discontinued by introducing biological disease-modifying antirheumatic drugs (bDMARDs) and the factors influencing the outcome. Method: We included RA patients who had been orally taking GCs at the initiation of bDMARDs. The changes in GC dose after starting bDMARDs were evaluated and the GC discontinuation rate was analyzed using Kaplan-Meier analysis. The factors associated with discontinuation of GCs were assessed by Cox hazard models. Results: Eighty RA patients were included in the study. The dosage of oral prednisolone (PSL) was significantly reduced from 5.0 to 3.0 mg/day by 3 months ( p =  .013). GCs were discontinued in 31.3% of patients and the median time until GC discontinuation was 10.1 months. The GC discontinuation rate was significantly higher in patients with Class 1 and 2 ( p  = .024), with an initial PSL dose <5 mg/day ( p  = .040), and with low DAS28(ESR) ( p  = .038). In multivariate analyses, higher DAS28(ESR) (odds ratio, 0.200; p  = .039), and higher PSL dose (odds ratio, 0.748; p  = .029) were significantly associated with less frequent GC discontinuation. Conclusion: DAS28(ESR) high and PSL dose were factors associated with discontinuation of GC use after starting bDMARDs.

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple immune cell subsets. We analyzed immune cell subsets in human peripheral blood mononuclear cells (PBMC) in order to identify the cells that are significantly associated with SLE disease activity and treatment. The frequencies of various subsets of CD4 + T cells, B cells, monocytes and NK cells in PBMC were assessed in 30 healthy controls (HC), 30 rheumatoid arthritis (RA) patients and 26 SLE patients using flow cytometry. The correlations between subset frequencies in SLE and clinical traits including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were examined. Changes in subset frequencies after the treatment in SLE patients were investigated. We focused on CD25 + LAG3 + T cells and investigated their characteristics, including cytokine secretion, mRNA expression and suppression capacity. We assessed correlations between CD25 + LAG3 + T cells and SLEDAI by Spearman's rank correlation coefficient. CD25 + LAG3 + T cells were significantly increased in SLE whereas there were few in RA and HC groups. CD25 + LAG3 + T cell frequencies were significantly correlated with SLEDAI and were increased in patients with a high SLEDAI score (> 10). CD25 + LAG3 + T cells produced both IL-17 and FOXP3, expressed mRNA of both FOXP3 and RORC and lacked suppressive capacity. CD25 + LAG3 + T cells were associated with disease activity of SLE. CD25 + LAG3 + T cells had features of both CD25 + FOXP3 + regulatory T cells (CD25 + Treg) and Th17. CD25 + LAG3 + T cells could be associated with the inflammatory pathophysiology of SLE.

Objectives: The characteristics of lymphoproliferative disorders (LPD) in patients with rheumatoid arthritis (RA) remain unclear. Therefore, we retrospectively analyzed the clinical characteristics of these patients in our department., Methods: Twenty RA patients who developed LPD between April 2003 and August 2016 in our department were analyzed., Results: All of the RA patients who developed LPD had been treated with methotrexate (MTX). The median weekly and total dosages of MTX were 6.8 mg/week and 2530 mg, respectively. The median duration of MTX administration was eight years. Nineteen patients (95%) achieved complete remission (CR) and 15 (75%) achieved CR with MTX cessation alone. Based on the pathological findings, we divided MTX-associated LPD patients into two groups (n = 16); polymorphic LPD (31%) and other groups. CR with MTX cessation alone was achieved in 5 (100%) and 6 (54.5%) patients in the polymorphic LPD and other groups, respectively (p = .12). Moreover, the duration from the cessation of MTX to CR was significantly shorter in the polymorphic LPD group than in the other group (5.3 months vs 12.6 months, p = .01, respectively)., Conclusion: Polymorphic LPD, which was the most frequent pathological diagnosis in this cohort, was associated with a higher incidence of CR and a significantly shorter duration to CR.

Background: Regulatory T cells (Tregs) play a role in the suppression of inflammation in autoimmune diseases, and lymphocyte activation gene 3 (LAG3) was reported as a marker of interleukin (IL)-10-producing Tregs. We aimed to clarify the function of human IL-10-producing CD4 + CD25 - LAG3 + T cells (LAG3 + Tregs) and their association with rheumatoid arthritis (RA)., Methods: LAG3 + Tregs of human peripheral blood mononuclear cells (PBMCs) were cultured with B cells and follicular helper T cells to examine antibody suppression effects. The frequency of LAG3 + Tregs was evaluated in peripheral blood samples from 101 healthy donors and 85 patients with RA. In patients treated with abatacept, PBMC samples were analyzed before and after treatment. Naive CD4 + T cells were sorted and cultured in the presence of abatacept, followed by flow cytometric analysis and function assays., Results: LAG3 + Tregs produced high amounts of IL-10 and interferon-γ, and they suppressed B-cell antibody production more strongly than CD25 + Tregs. Cell-to-cell contact was required for the suppressive function of LAG3 + Tregs. The frequency of LAG3 + Tregs was lower in patients with RA, especially those with higher Clinical Disease Activity Index scores. LAG3 + Tregs significantly increased after 6 months of abatacept treatment, whereas CD25 + Tregs generally decreased. Abatacept treatment in vitro conferred LAG3 and EGR2 expression on naive CD4 + T cells, and abatacept-treated CD4 + T cells exhibited suppressive activity., Conclusions: IL-10-producing LAG3 + Tregs are associated with the immunopathology and therapeutic response in RA. LAG3 + Tregs may participate in a mechanism for the anti-inflammatory and immune-modulating effects of targeted therapy for costimulation.