Synovitis and its association with elevated circulating interferons and hydroxychloroquine response in discoid lupus erythematosus: a cross-sectional studyStec, Krezelok, Awsiuk
et alRheumatol Int (2025) 45 (3), 64
Abstract: A significant proportion of patients with discoid lupus erythematosus (DLE) experience joint pain, yet its underlying pathomechanism remains unclear. Recent ultrasound studies in systemic lupus erythematosus (SLE) patients indicate synovitis in up to 90%, even in clinically silent cases, with interferon-mediated immune responses implicated in joint inflammation. This study aimed to investigate joint pathology in DLE, focusing on synovitis and its immunological profile. We analyzed 23 patients with histologically confirmed DLE and joint pain, all treated for ≥ 5 months with prednisone (≤ 10 mg/day) and hydroxychloroquine (HCQ, 200 mg/day). Ultrasonographic assessment (24 joints per patient) was performed using power Doppler (PD) ultrasonography, with synovitis graded using the OMERACT-EULAR PDUS synovitis score. Serum levels of 37 cytokines were measured via Bio-Plex Pro™ Human Inflammation Panel (37Plex). Synovitis (OMERACT-EULAR score ≥ 1) was identified in 30% (7/23) of DLE patients, with minimal (grade 1) synovitis in six cases and moderate (grade 2) synovitis in one. Patients with synovitis had significantly higher levels of IFN-α2, IFN-γ, MMP-1, MMP-3, sTNF-R1, and sTNF-R2 (p < 0.05), more painful joints, and poorer response to HCQ treatment (71.4% vs. 25% non-responders). Joint pain in DLE may result from synovitis, with an interferon-mediated immune response contributing to inflammation. Patients with synovitis exhibited elevated interferon levels and a worse response to HCQ therapy. These findings suggest a shared pathogenic mechanism between DLE and SLE-related arthritis, warranting further investigation into targeted therapeutic strategies.© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Experimental efficacy of vaccination of weaned piglets with a modified-live commercial PRRS virus vaccine against the challenge with a Spanish highly virulent PRRSV-1 strainCortey, Jiménez, Aguirre
et alPorcine Health Manag (2025) 11 (1), 10
Abstract: In 2020, a highly virulent PRRSV-1 strain emerged in Spain and rapidly spread across the country. The purpose of the present study was to test in a piglet model whether a commercial PRRSV-1 modified live vaccine was able to confer protection against strain R1, a representative of the emerging clade. For that purpose, two groups of 26 piglets were either vaccinated intradermally or kept as controls; 42 days later, half of the animals in each group were intranasally challenged with the R1 strain. Then, animals were followed to assess the development of clinical signs (until 14 days post-challenge), lung lesions (10- and 35-days post-challenge), weight gains, viremia and nasal shedding and the immune response (anti PRRS virus nucleoprotein antibodies) by ELISA and virus specific-interferon-γ secreting cells by ELISPOT).Challenge of naïve pigs resulted in high fever (up to 41.9 °C), lethargy and severely retarded growth (0.748 kg/day). In contrast, vaccinated/challenged pigs had less fever and for a shorter period, lower clinical scores and a higher average daily weight gain (0.940 kg/day), comparable to the unchallenged animals. At 10 days-post challenge, in naïve animals on average 49.1% of the lung was pneumonic (range 8-81%) while in vaccinated animals the average was 15.7% (4-41%). Duration of viremia was reduced in vaccinated animals and after 14 days post-challenge, most were negative by RT-qPCR. In contrast, 50% of the naïve/challenged pigs remained viremic at 35 days post-challenge. Vaccination induced rapid seroconversion and challenge of naïve animals resulted in 100% of ELISA-positive pigs by day 14 post-challenge. Regarding the development of IFN-γ responses, for vaccinated animals the frequencies increased until day 35 post-vaccination. After challenge, in vaccinated pigs, the peak of the R1-specific IFN-γ response was reached at 14 days and then the viremia ceased, although nasal shedding persisted in some vaccinated animals.In the present trial, vaccination resulted in improved clinical course, better weight gain and reduced viremia. At the peak of the infection, lung lesions were reduced in most animals although some individuals still had extensive pneumonia. In summary, vaccination was shown to provide partial but significant protection against the highly virulent R1 strain.© 2025. The Author(s).
Dendritic cells pulsed with multifunctional Wilms' tumor 1 (WT1) peptides combined with multiagent chemotherapy modulate the tumor microenvironment and enable conversion surgery in pancreatic cancerKoido, Taguchi, Shimabuku
et alJ Immunother Cancer (2024) 12 (10)
Abstract: We aimed to develop a chemoimmunotherapy regimen consisting of a novel Wilms' tumor 1 (WT1) peptide-pulsed dendritic cell (WT1-DC) vaccine and multiagent chemotherapy and to investigate the safety, clinical outcomes, and WT1-specific immune responses of patients with unresectable advanced pancreatic ductal adenocarcinoma (UR-PDAC) who received this treatment.Patients with UR-PDAC with stage III disease (locally advanced (LA-PDAC; n=6)), stage IV disease (metastatic (M-PDAC; n=3)), or recurrent disease after surgery (n=1) were enrolled in this phase I study. The patients received one cycle of nab-paclitaxel plus gemcitabine alone followed by 15 doses of the WT1-DC vaccine independent of chemotherapy. The novel WT1 peptide cocktail was composed of a multifunctional helper peptide specific for major histocompatibility complex class II, human leukocyte antigen (HLA)-A*02:01, or HLA-A*02:06 and a killer peptide specific for HLA-A*24:02.The chemoimmunotherapy regimen was well tolerated. In the nine patients for whom a prognostic analysis was feasible, the clinical outcomes of long-term WT1 peptide-specific delayed-type hypersensitivity (WT1-DTH)-positive patients (n=4) were significantly superior to those of short-term WT1-DTH-positive patients (n=5). During chemoimmunotherapy, eight patients were deemed eligible for conversion surgery and underwent R0 resection (four patients with LA-PDAC, one patient with M-PDAC, and one recurrence) or R1 resection (one patient with M-PDAC), and one patient with LA-PDAC was determined to be unresectable. Long-term WT1-DTH positivity was observed in three of the four patients with R0-resected LA-PDAC. These three patients exhibited notable infiltration of T cells and programmed cell death protein-1+ cells within the pancreatic tumor microenvironment (TME). All patients with long-term WT1-DTH positivity were alive for at least 4.5 years after starting therapy. In patients with long-term WT1-DTH positivity, the percentage of WT1-specific circulating CD4+ or CD8+ T cells that produced IFN-γ or TNF-α was significantly greater than that in patients with short-term WT1-DTH positivity after two vaccinations. Moreover, after 12 vaccinations, the percentages of both circulating regulatory T cells and myeloid-derived suppressor cells were significantly lower in patients with long-term WT1-DTH-positive PDAC than in short-term WT1-DTH-positive patients.Potent activation of WT1-specific immune responses through a combination chemoimmunotherapy regimen including the WT1-DC vaccine in patients with UR-PDAC may modulate the TME and enable conversion surgery, resulting in clinical benefits (Online supplemental file 1).jRCTc030190195.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Elucidating the beneficial impact of exercise on chronic obstructive pulmonary disease and its comorbidities: Integrating proteomic and immunological insightsWang, Liu, Liang
et alBr J Pharmacol (2024) 181 (24), 5133-5150
Abstract: Physical activity is an effective therapeutic protocol for treating chronic obstructive pulmonary disease (COPD). However, the mechanisms underlying the benefits of physical activity in COPD are not fully elucidated.In a mouse model of COPD, analysis of biological markers and lung proteomics identified the molecular pathways through which exercise ameliorates COPD.Exercise improved pulmonary function, emphysema, small airway disease, pulmonary inflammation, glucose metabolic dysregulation, and insulin resistance in COPD mice. Proteomic analysis revealed 430 differentially expressed proteins (DEPs) between the COPD and COPD + Exercise (COPD + Ex) groups. GO analysis indicated that the enriched pathways were predominantly related to the immune response, inflammatory processes, insulin secretion, and glucose metabolic processes. GO analysis revealed IL-33 as a crucial target for the exercise-related amelioration of COPD. KEGG analysis showed that DEPs were significantly enriched in primary immunodeficiency, the intestinal immune network for IgA production, and the NF-κB signalling pathway. Exercise inhibited NF-κB activation by suppressing the CD14/TLR4/MyD88 and TNF-α/TNF-R1/TRAF2/5 pathways in COPD mice. Exercise inhibited expression of BCR, IgM, IgD, IgG, IgE, and IgA by suppressing B-cell receptor signalling. Exercise attenuated glucose metabolic dysregulation and insulin resistance through the suppression of proinflammatory mediators, including MHC I, MHC II, TNF-α, IFN-γ, and IL-1β, while concurrently increasing insulin expression. The qRT-PCR results were consistent with the proteomic results.In a mouse model, exercise improved COPD and its metabolic comorbidities through immune system regulation and inflammation suppression, offering insights into potential therapeutic targets.© 2024 British Pharmacological Society.
膜杰作
Star Staining
