To evaluate real-world use of advanced cardiovascular imaging in less common and rare rheumatic immune-mediated inflammatory diseases (IMIDs) and identify variation in practice to inform future studies and clinical guidelines. A retrospective, multi-centre quality improvement project was conducted across four major hospitals in the UK. Adults with systemic lupus erythematosus, systemic sclerosis, inflammatory myopathy, vasculitis or primary Sjögren's disease who underwent cardiac magnetic resonance (CMR), CT coronary angiography (CTCA) or positron emission tomography (PET) between January 2023 and December 2024 were included. Demographics, underlying IMID, cardiovascular risk factors, imaging indications, findings and management were extracted using a standardised proforma and analysed. A total of 294 imaging studies were performed in 261 patients (72.4% female, 65.9% aged 40-74 years) comprising 137 (46.6%) CMR, 40 (13.6%) CTCA, and 117 (39.8%) PET scans. Indications varied by modality and centre. Cardiovascular abnormalities were reported in 175/294 (59.5%), most commonly in vasculitis (53.7%). Notably, 54/63 (85.7%) of abnormal PET and 61/89 (68.5%) of abnormal CMR scans were in asymptomatic patients. Imaging findings prompted cardiology referral/ongoing follow-up in 59.5% and changes to IMID treatment in 31.3%, but only 23.1% were discussed in a formal multidisciplinary team (MDT). Advanced cardiovascular imaging frequently identifies cardiovascular involvement in rheumatic IMIDs, including in asymptomatic patients. Treatment adjustments occurred in a third of patients, although largely undertaken outside established MDT processes. These findings emphasise the need for better understanding of imaging-based findings and for cardio-rheumatology MDTs to support integrated decision-making to improve patient outcomes.

The pro-inflammatory cytokines IFN-α and TNF-α inhibit organoid-derived extravillous trophoblast invasion.

Hidradenitis suppurativa (HS) is achronic, relapsing, immune-mediated inflammatory disease of the terminal hair follicle unit, characterized by inflamed nodules, abscesses, draining tunnels, scarring, pain, and substantial impairment of quality of life. Current guideline-based management is multimodal and combines general measures, pain management, antiseptic and antibiotic strategies, systemic anti-inflammatory therapy, and, where appropriate for selected lesions, surgical procedures. According to European treatment standards, systemic treatment options for moderate-to-severe HS include antibiotics as well as approved biologic therapies, particularly adalimumab and the IL-17-targeted agents secukinumab and bimekizumab. This narrative review summarizes therapeutic agents currently under clinical investigation for HS. The analysis is primarily based on ClinicalTrials.gov, supplemented by published clinical studies. The therapeutic pipeline is broad and includes the following: IL-17-, IL-36-, and IL-1-targeted biologics; intracellular kinase inhibitors; dual immunomodulatory antibodies; chemokine-, complement-, and neutrophil-directed strategies; topical agents; PDE4 inhibition; and metabolic approaches. The diversity of emerging therapeutic strategies highlights the persistently high unmet need in HS. These approaches target distinct components of both the adaptive and innate immune systems. Given the immunological heterogeneity of HS, such broad and partly multimodal strategies appear biologically plausible and clinically meaningful. Beyond purely immunologically acting therapies, GLP‑1 receptor agonists represent an interesting complementary approach and may, in combination with immunosuppressive therapies, provide added benefit and generate promising clinical data.

PET imaging of polymyalgia rheumatica: update and future trends.

Pediatric ulcerative colitis (UC) is a chronic, immune-mediated inflammatory disease of the colon, characterized by dysregulated immune response. This condition significantly impacts growth, development, and quality of life, highlighting the need for effective therapeutic strategies. This report reviews current pharmacologic treatments for pediatric UC, including conventional (aminosalicylates, corticosteroids, immunomodulators) and advanced therapies (biologics, small molecules). It discusses their mechanisms, efficacy, and safety, highlights challenges such as inadequate response and the need for precision medicine, and summarizes emerging therapies, ongoing pediatric trials, and novel agents under development. A comprehensive literature search of PubMed, Embase, and Cochrane Library databases (1987-2026) identified 100 studies: 67 pediatric-specific and 33 adult studies. The review included randomized controlled trials, observational studies, systematic reviews, and clinical practice guidelines (ECCO-ESPGHAN, NASPGHAN). Optimal management of pediatric UC requires a personalized approach that balances efficacy and safety while anticipating long-term outcomes. Integration of novel biologics, targeted therapies, and precision medicine strategies holds promise for improving disease control, minimizing adverse effects, and enhancing quality of life in affected children.

Background: Ulcerative colitis is a chronic immune-mediated inflammatory disease characterized by widespread inflammation in the colon's mucosal layer. Experimentally induced models in animals aid in describing the immunopathogenesis and help discover novel therapeutic approaches. Objectives: This study aimed to investigate the histopathological alterations, immune response, and apoptosis in the colonic tissues of patients and mice with experimentally induced colitis. Methodology: Colonic tissues from ulcerative colitis patients were collected following surgical operations. Dextran sulfate sodium (DSS) was administered to induce colitis in BALB/c mice. Both colonic tissue samples of humans and mice were processed for histopathological investigation. Additionally, immunohistochemistry was performed to characterize CD3, CD20, CD68, and caspase-3 tissue markers. Results: DSS-induced colitis affected both sexes of mice, with males exhibiting more severe symptoms. Numerous histopathological alterations were detected in the colonic tissues of patients and induced mice compared to control mice, including surface ulceration and erosion, cryptitis, crypt distortion, and various inflammatory cell infiltrations. Moreover, abscesses were detected in the human colonic tissue. The immunohistochemical study revealed that CD3 was the most abundant inflammatory cell in the colonic tissues of patients and mice, followed by CD20 (B cells) and CD68 (macrophages). Caspase-3 expression was identified in all samples, revealing diverse levels, and was particularly prominent in mice, which recorded a high score. Conclusion: The remarkable inflammatory reactions documented in the colon tissue by the current study confirm the importance of understanding the inflammatory responses responsible for ulcerative colitis.

Plaque psoriasis (PP) is a chronic immune-mediated inflammatory disease driven by dysregulation of the IL-23/Th17/IL-17 axis. Although IL-17A targeted biologics achieve robust clinical efficacy, how cytokine blockade is accompanied by systemic immune remodeling during disease control remains incompletely understood. The objective was to characterize changes in circulating T-cell subsets associated with clinical response to IL-17A blockade and to examine the relationship between PD-1 engagement and Th17 effector activity. Longitudinal immune profiling was performed in seven patients with PP before and after achieving a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) following secukinumab treatment. Circulating T-cell subsets, PD-1 expressing populations, and cutaneous lymphocyte antigen positive (CLA+) T cells were quantified by flow cytometry, with plasma cytokine profiling. Ex vivo T-cell responses to the PD-1 agonist peresolimab were assessed in an independent cohort. At baseline, patients exhibited reduced frequencies of regulatory T cells compared with healthy controls. Following PASI 90, circulating Th17 and Th2 cell frequencies increased despite minimal sustained changes in plasma cytokines, indicating dissociation between effector T-cell expansion and soluble mediators during IL-17A blockade. Circulating CD4+CLA+T cells were partially restored. Treatment was accompanied by increased frequencies of PD-1 expressing CD4+T-cell subsets, which showed an inverse association with disease activity over time. Ex vivo PD-1 engagement selectively reduced IL-17A producing CD4+ T cells, with limited effects on IFN-γ. PD-1 likely restrains Th17 activity during IL-17A blockade, a hypothesis that warrants validation in larger cohorts. Successful therapy in PP appears to reflect immune reorganization through PD-1/Th17 interactions, rather than systemic suppression.

JAAD Game Changers: "Venous thromboembolism risk is lower in patients with atopic dermatitis than other immune-mediated inflammatory diseases: A retrospective, observational, comparative cohort study using US claims data".

Psoriasis is a chronic, immune-mediated inflammatory disease with heterogeneous manifestations. Reliable biomarkers reflecting disease severity and treatment response remain limited. Glycans-carbohydrate structures attached to proteins and lipids-play key roles in biological processes, contributing to functional specificity. Abnormal glycosylation has been implicated in the pathogenesis of inflammatory and neoplastic diseases, highlighting their potential as therapeutic targets and biomarkers. This study aimed to evaluate serum N-glycan profiles as potential biomarkers for psoriasis, focusing on the ratio of sialylated biantennary N-glycan (S) to fucosylated asialo-biantennary N-glycan (FA), termed the S/FA ratio. Serum samples from 45 patients with psoriasis, 12 with atopic dermatitis (AD), and 19 healthy controls were analyzed using high-performance liquid chromatography. The performance of the S/FA ratio was compared with reported biomarkers (CRP and CCL20), and its associations with Psoriasis Area and Severity Index (PASI) and treatment response were examined. The S/FA ratio was significantly higher in psoriasis than in healthy controls (p < 0.001) and correlated with PASI (r = 0.485, p < 0.001) and its components. Receiver operating characteristic analysis showed comparable diagnostic accuracy among the S/FA ratio (AUC = 0.788, sensitivity: 73.7%, specificity: 73.3%), CRP (AUC = 0.780), and CCL20 (AUC = 0.741). Changes in the S/FA ratio were correlated with improvements in PASI after systemic treatment (r = 0.467, p = 0.002), including a patients subgroup receiving IL-23 inhibitors. The S/FA ratio was not significantly influenced by demographics, comorbidities, or arthralgia. No significant difference was observed between psoriasis and AD, and the S/FA ratio was not significantly elevated in AD compared with healthy controls. The serum S/FA ratio may serve as a glycan-based biomarker associated with disease severity and treatment response in psoriasis, although its ability to distinguish psoriasis from other inflammatory diseases requires further validation in larger and treatment-naïve cohorts.

Adaptive immune responses against Lachnospiraceae-derived flagellins and their role in inflammatory bowel disease.

Atopic dermatitis (AD) is a chronic immune-mediated inflammatory skin disease characterized by a complex and dynamic interplay between immune dysregulation and epidermal barrier dysfunction. Emerging evidence supports an integrated pathogenic model in which immune activation and barrier impairment form a bidirectional and self-reinforcing axis rather than representing separate processes. This review synthesizes current knowledge on the role of IL-4/IL-13-dependent signaling in regulating keratinocyte lipid metabolism and its impact on epidermal barrier integrity. IL-4/IL-13 signaling via the JAK-STAT pathway, particularly STAT6, contributes to keratinocyte dysfunction, resulting in impaired differentiation and coordinated alterations in lipid metabolism, including fatty acid elongation and ceramide synthesis. These cytokine-driven processes disrupt the organization of the stratum corneum lipid matrix, resulting in increased transepidermal water loss, enhanced skin permeability, and susceptibility to microbial colonization, thereby promoting chronic inflammation. Collectively, these findings support the concept that IL-4/IL-13-mediated dysregulation of keratinocyte lipid metabolism may represent an important immunometabolic mechanism linking type 2 inflammation with secondary barrier dysfunction in atopic dermatitis, thereby contributing to disease persistence. Targeting both immune pathways and epidermal lipid homeostasis may represent an effective strategy to restore barrier function and improve clinical outcomes.

Ulcerative colitis (UC) is a chronic, relapsing, immune-mediated inflammatory disease of the colonic mucosa that imposes a substantial and growing global health burden. The pathophysiological basis of UC encompasses a multifactorial interplay among genetic predisposition, dysregulated innate and adaptive immune responses, gut microbiome dysbiosis, epithelial barrier dysfunction, and environmental triggers. Despite considerable advances in therapeutic strategies over the past two decades ranging from aminosalicylates and corticosteroids to biologic agents targeting TNF-α, integrins, and the IL-12/23 axis, as well as small molecule modulators such as JAK inhibitors and sphingosine-1-phosphate receptor agonists-a substantial proportion of patients either fail to achieve remission or experience loss of response over time, underscoring the continued need for novel therapeutic approaches. This comprehensive review systematically addresses the definition, epidemiology, socioeconomic burden, and unmet clinical needs in UC. The molecular and cellular underpinnings of the disease are discussed in depth, including the roles of key signaling pathways, pattern recognition receptors, cytokine networks, and the gut-immune interface. Clinical features, diagnostic criteria, endoscopic and histological scoring systems, and validated disease activity indices are also described. Current pharmacological therapies are reviewed with regard to mechanisms of action, pivotal clinical trial data, and safety profiles. Emerging investigational strategies including precision biologic agents, next-generation small molecules, microbiome-based therapeutics, and cell and gene therapy approaches are evaluated within a translational framework. A curated synthesis of experimental models of UC induction in rodents is presented, followed by structured tabular summaries of selected naturally derived bioactive compounds and pharmacological drug candidates that have demonstrated protective efficacy in preclinical models of UC. Compounds were selected for tabular inclusion on the basis of three prespecified criteria: (i) availability of at least one peer-reviewed in vivo study conducted in a validated experimental colitis model (DSS, TNBS, and acetic acid); (ii) a clearly described and mechanistically plausible basis of action relevant to UC pathophysiology; and (iii) representation across the principal mechanistic clusters identified in this review. Application of these criteria to the studies included in the final review yielded 29 naturally derived bioactive compounds (Table1) and 26 pharmacological drug candidates (Table2) for structured synthesis.

Psoriasis is a multisystemic, immune-mediated inflammatory disease characterized by high recurrence rates upon treatment cessation. Biotherapeutics are highly anticipated for treating psoriasis via transdermal delivery. However, the topical administration of potent immunomodulators is fundamentally hindered by the stratum corneum barrier, stringent molecular size constraints, and rapid proteolytic degradation within the skin microenvironment. Here, we report the development of transdermal lipopeptide liposomes (TLLs) designed for the site-specific delivery of a double-bridged cyclic tetradecapeptide (CTP)─a metabolically stable inhibitor of interleukin-17 (IL-17). The TLL platform utilizes engineered, asymmetric Y-shaped lipopeptides that transiently disrupt keratin and lipid organization, facilitating deep-seated penetration into psoriatic lesions. We demonstrate that protease-resistant CTP enables sustained antagonism of the IL-17 axis. In a preclinical model, TLL treatment significantly alleviated inflammatory symptoms and, crucially, suppressed rebound pathology and disease recurrence by remodeling both the local immune landscape and cutaneous biomechanics. This work establishes a clinically translatable framework that bridges the high efficacy of systemic biologics with the localized convenience of topical delivery, offering a transformative, patient-centric alternative to parenteral biologic therapies.

The Evolving Landscape of JAK-STAT Inhibition in the Treatment of Immune Mediated Inflammatory Diseases.

Multiple sclerosis (MS) is an immune-mediated inflammatory and neurodegenerative disease of the central nervous system (CNS) that leads to demyelination, axonal injury, and progressive disability. Glucagon-like peptide1 receptor agonists (GLP-1RAs) have been proposed as adjunctive therapy with potential neuroprotective properties. We evaluated the effects of GLP-1RA treatment on metabolic parameters, functional performance, and biomarkers of neurodegeneration in relapsing-remitting MS (RRMS). In this prospective, randomized, open-label, single-center proof-of-concept study, 28 patients with RRMS receiving stable natalizumab treatment were randomized to adjunctive GLP-1RA (dulaglutide; 0.75mg subcutaneously once weekly for 12months; n = 15) or to a control group without adjunctive therapy (n = 13). Assessments were performed at baseline and 12months. Primary outcomes included plasma neurofilament light chain (NfL) and brain magnetic resonance imaging (MRI) volumetry. Secondary outcomes included resting metabolic rate, functional performance (Timed 25-Foot Walk [T25FW] and 9-Hole Peg Test [9HPT]), cognitive performance (Symbol Digit Modalities Test [SDMT]), anthropometric and metabolic measures, and oral glucose tolerance test (OGTT)-derived insulin sensitivity indices. Dulaglutide significantly reduced weight, body mass index (BMI), body fat, and visceral fat, and improved glucose tolerance (reduced glucose area under the curve [AUC]). No adverse events were recorded in either group; no discontinuations occurred. Exploratory analyses indicated trends toward improved walking speed (T25FW, group × time interaction: F1,26 = 9.4, p = 0.005) and non-dominant hand manual dexterity (9HPT, F1,26 = 4.7, p = 0.039) in the dulaglutide group. However, no significant between-group differences were observed in plasma NfL, brain MRI volumetric measures, or cognitive performance. Adjunctive dulaglutide 0.75mg weekly for 12months improved metabolic parameters and showed exploratory signals of functional benefit, but did not modify plasma NfL or MRI volumetric measures in natalizumab-treated RRMS. Larger, adequately powered studies with higher-dose GLP-1RA regimens and longer follow-up are warranted. The trial was registered in the EU Clinical Trials Register (EudraCT 2019-003001-94).

The concept of difficult-to-treat (D2T) disease is increasingly recognized across immune-mediated inflammatory diseases, and was recently introduced in spondyloarthritis (SpA). Several terms, including difficult-to-manage (D2M), complex-to-manage (C2M), and treatment-refractory (TR) describe disease states characterized by persistent symptoms and inadequate response to targeted therapies. This review aims to clarify the emerging constructs of D2M and TR disease in axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), and their implications for emerging research in this area. Recent initiatives from ASAS, EULAR, and GRAPPA have proposed definitions to frame D2T clinical scenarios in axSpA and PsA. These converge on distinguishing treatment-refractory disease, characterized by persistent objective inflammation despite multiple targeted therapies, from broader D2M/C2M states driven by multifactorial contributors including non-inflammatory factors. Emerging data suggest that clinical and biological heterogeneity across disease domains may contribute to these phenotypes. Challenging phenotypic presentations often display overlapping features between axSpA and PsA, supporting the concept of a continuum across the SpA spectrum. Distinguishing TR disease from broader D2M/C2M states is essential for avoiding inappropriate treatment escalation, and supporting personalized multidisciplinary care. Further research is needed to validate these definitions, determine contributing factors and their prevalence, and clarify the molecular mechanisms underlying treatment refractory disease.

Immune-mediated inflammatory diseases (IMIDs), including psoriasis, lupus, multiple sclerosis, and inflammatory bowel disease, are chronic conditions characterized by immune dysregulation and excessive inflammatory cytokine expression. Biologic therapies have transformed IMID management, and the introduction of biosimilars has improved treatment accessibility by reducing costs and alleviating the burden on healthcare systems. Despite regulatory approval and demonstration of similarity to reference biologics, biosimilar adoption remains limited due to uncertainties regarding interchangeability and extrapolation, insufficient communication among stakeholders, and the nocebo effect that influences patient and physician confidence. Although regulatory agencies provide detailed guidance and European Public Assessment Reports, regulatory and perceptual barriers persist in clinical practice. This work reviews real-world and clinical trial data on switching from reference biologics to biosimilars in IMIDs and demonstrates comparable safety and efficacy outcomes. However, patient perceptions and communication strategies significantly influence treatment success. Despite the available evidence, negative perceptions and a lack of confidence persist among both patients and healthcare professionals. Promoting understanding and confidence in biosimilars can increase access and availability and, consequently, enhance the benefits associated with their wider use. Therefore, addressing educational, regulatory, and clinical practice gaps is essential for optimizing biosimilar integration in IMID management.

Promoting intestinal regeneration without tumor risk in immune-mediated inflammatory diseases.

Background Psoriasis is a chronic immune-mediated inflammatory disease increasingly associated with other autoimmune disorders, including autoimmune thyroid diseases, particularly Hashimoto’s thyroiditis. In recent years, numerous studies have investigated the relationship between psoriasis and thyroid dysfunction; however, the available evidence remains partly inconsistent. Objective The aim of this study was to evaluate the association between psoriasis and autoimmune thyroid diseases based on available observational studies, systematic reviews, and meta-analyses. Methods A literature review was conducted using publications available in PubMed, PMC, Frontiers, and MDPI databases. Observational studies, systematic reviews, meta-analyses, and Mendelian randomization studies investigating the relationship between psoriasis and thyroid diseases were included. Data regarding the prevalence of AITD, thyroid autoantibodies, and thyroid dysfunction in patients with psoriasis were analyzed. Results Available evidence indicates that patients with psoriasis have an increased risk of autoimmune thyroid diseases. In the meta-analysis by Zhang et al., including 253,313 psoriasis patients and 1,376,533 controls, psoriasis was associated with a significantly increased risk of AITD (OR = 1.76; 95% CI: 1.35–2.28), particularly Hashimoto’s thyroiditis (OR = 1.88; 95% CI: 1.50–2.35). Observational studies also demonstrated higher levels of anti-TPO and anti-TG antibodies, more frequent thyroid dysfunction, and ultrasonographic changes suggestive of thyroid autoimmunity among psoriasis patients. Conclusions Psoriasis is associated with an increased prevalence of autoimmune thyroid diseases, especially Hashimoto’s thyroiditis. The observed relationship may result from shared immunological and genetic mechanisms. Further prospective and causal studies are required to better understand the nature of this association.

Icotrokinra (ICOTYDE™) is a targeted oral peptide interleukin (IL)-23 receptor (IL-23R) antagonist being developed by Johnson & Johnson, and Protagonist Therapeutics, Inc., for the treatment of immune-mediated inflammatory diseases. In March 2026, the US FDA approved icotrokinra for the treatment of moderate-to-severe plaque psoriasis (PsO) in adults and paediatric patients ≥ 12 years of age and who weigh ≥ 40 kg who are candidates for systemic therapy or phototherapy. Icotrokinra is also under review for this indication in the EU and in Canada. This article summarizes the milestones in the development of icotrokinra leading to this first approval for moderate-to-severe plaque PsO.