Develop recommendations for multidisciplinary, multisector care providers involved in supporting individuals with alopecia areata (AA) to promote their well-being of these individuals. AA is a condition that causes hair loss on the scalp and, for some, the head or whole body and is associated with difficulties in psychosocial adjustment. A modified Delphi consensus study with three rounds: round 1 was a qualitative survey to generate recommendations; round 2 involved a rating survey to work towards consensus on important items to retain and round 3 asked panellists from four different support roles to establish the most relevant items for their respective roles. The UK, across healthcare, charitable and private health and mental health sectors. Panellists held two forms of expertise. One group consisted of experts in support roles, comprising medical professionals (general practitioners and dermatologists), mental health professionals, peer facilitators and trichologists. All were selected due to their experience of working with individuals who have AA. The other group consisted of experts by experience, namely adults living with AA who had some experience of receiving support from the above care providers. 48 panellists contributed to round 1 (22 experts by support role, 29 experts by experience and 3 with dual roles), 46 to round 2 (21 experts by support role, 27 experts by experience and 3 with dual roles) and 23 experts by support role completed round 3. In round 1, data were analysed using qualitative content analysis. In round 2, panellists rated the importance of all recommendation items on a single 1-5 scale. Consensus was determined by ≥80% agreement between panellists that items were moderately or very important. Multiple candidate recommendations were generated from round 1, and following round 2,
Introduction Chronic inflammation and immune cell communication underpin a wide range of chronic diseases, yet population-scale maps integrating systemic inflammatory, metabolic and proteomic signals across multiple disease states are scarce. Methods Using UK Biobank, we classified participants into six baseline groups—healthy controls, cancer, autoimmune, infectious, metabolic diseases, and multiple comorbidities. We profiled clinical and hematological indices, NMR-based metabolites and Olink proteomics, and trained four multi-class deep learning models (clinical/inflammatory only; +NMR; +Olink; three-tower multi-omics) with 10-fold cross-validation. Out-of-fold predicted probabilities were combined in a stacking meta-model to derive machine-learning risk scores for “any chronic disease.” Shapley value analyses were used to identify key features reflecting systemic immune and metabolic communication. Cause-specific cumulative incidence and Fine–Gray competing-risks models evaluated associations between these risk scores and cancer-related and non-cancer mortality, adjusting for conventional risk factors. To provide biological validation of model-prioritized immune mediators (BAFF [TNFSF13B], GDF15, IL-15 and CD276), we performed in vitro stimulation of healthy-donor PBMCs by ELISA, flow cytometry, and qPCR. Results We observed pronounced and pathway-specific heterogeneity of inflammatory markers, lipid-related metabolites and immune–inflammatory proteins across disease groups. Omics-augmented deep learning models outperformed the clinical-only model, and the stacking ensemble achieved the best accuracy, macro-F1 and multi-class AUC. Machine-learning–derived risk scores showed monotonic gradients in cancer and other-cause death and remained independently associated with several cause-specific outcomes. In vitro validation supported myeloid inflammatory inducibility of model-highlighted mediators. Conclusions By integrating multi-omics deep learning with competing-risks modelling, this study decodes population-level immune–metabolic communication patterns across chronic disease states, linking shared inflammatory and proteomic signatures to long-term mortality and providing a quantitative framework to support future, mechanism-focused and immunologically informed risk stratification.
Bradykinin (BK) is a biologically active nanopeptide that plays a crucial role within the kallikrein-kinin system (KKS), a complex network involved in the regulation of vascular tone, epithelial cell ion transport, vascular permeability, mucosal secretion, release of cytokines from leukocytes among others. Over the past decades, BK has attracted sustained scientific interest due to its pleiotropic effects observed across various tissues and pathological conditions. Recent advances have significantly broadened our understanding of BK's role in modulating inflammatory and immune processes. Notably, accumulating evidence indicates that BK can exert dual and context-dependent effects-either pro-inflammatory or anti-inflammatory-depending on the cellular environment, receptor subtype activation (BK1R vs BK2R), and crosstalk with other signaling pathways. Emerging studies highlight that BK receptors may interact with another surface molecules expressed on immune cells, including T cell receptors (TCR) and immune checkpoint proteins such as PD-L1. These interactions suggest that BK signaling may be in a center of crucial immunoregulatory mechanisms influencing leukocyte activation status. Such findings may have important implications for understanding immune homeostasis and for designing novel therapeutic strategies. In cancer, BK is suggested to contribute to tumor progression through the promotion of cancer stem cells and immunosuppressive microenvironment formation, whereas in autoimmune diseases, its modulation could attenuate excessive immune activation and tissue damage. Therefore, the dual nature of BK action positions it as both a potential therapeutic target and a modulatory agent depending on disease context. This review summarizes current knowledge on the multifaceted roles of BK in inflammation and immunity, emphasizing its molecular mechanisms, receptor dynamics, and potential therapeutic applications. Special attention is given to the interplay between BK signaling and regulatory membranous proteins, offering a framework for future research aimed at exploiting
The aim of the work was to develop and validate an anti-drug antibody (ADA) assay for RGB-19, a proposed biosimilar to tocilizumab, capable of detecting anti-tocilizumab antibodies in the presence of high concentrations of soluble IL-6 receptor (sIL-6R), the drug's pharmacological target. A bridging electrochemiluminescent immunoassay was applied. To mitigate target interference, sarilumab - a high-affinity anti-sIL-6R antibody - was incorporated into the sample preparation. The assay was validated per EMA and FDA guidelines. The assay demonstrated high sensitivity, robust precision, and selectivity across normal and diseased matrices. Drug tolerance exceeded 280 µg/mL at regulatory sensitivity thresholds, and target tolerance was confirmed up to 1000 ng/mL sIL-6R. Performance monitoring during Phase I and III clinical sample analysis confirmed stability and acceptable false-positive rates. The validated ADA assay effectively neutralized sIL-6R interference and provided reliable immunogenicity assessment for RGB-19 clinical trials. Its robustness supports biosimilarity evaluation and ensures compliance with regulatory standards. Validation of this ADA assay is essential for regulatory compliance and patient safety. By ensuring accurate ADA detection under clinically relevant conditions, it supports biosimilarity demonstration and streamlines regulatory review, ultimately facilitating timely access to cost-effective biologic therapies. https://jrct.mhlw.go.jp. jRCT2031230029 and jRCT2031220512.
Chimeric antigen receptor T (CAR-T) cells demonstrate remarkable effectiveness in targeting and eliminating pathogenic B-cell lineages, showing significant specificity and efficacy against B cell malignancies. In addition, CAR-T cell-mediated B cell depletion and resetting, which showed great potential in treating autoimmune diseases, thereby extending the clinical applicability of adoptive cell therapy. In this review, we examine the progression of CAR-T targeted B cell therapy for autoimmune diseases, encompassing the development of new therapeutic strategies and reports on related clinical outcomes. Furthermore, the article delves into the challenges and potential avenues for enhancement related to the safety aspects and inherent limitations of current technological solutions.