Posters

ZNFX1 is a zinc-finger helicase that binds viral RNA and triggers a type I interferon response. Pathogenic biallelic ZNFX1 variants cause ZNFX1 deficiency, an inborn error of immunity (IEI) predisposing to severe viral infections and multisystem inflammation.

We performed a combined retro- and prospective international multicentered study of 35 patients, including 20 previously unreported cases. We identified 14 novel variants. Seventeen different virus species were detected during inflammatory episodes. Most patients experienced severe inflammatory episodes within the first year of life; 15 met the revisited 2004 HLH criteria. Lung involvement was present in 27 patients (77%), neurological involvement in 13 (37%), and renal involvement in 15 (43%). Pulmonary hemorrhage occurred in eight patients. Of 17 deceased patients, 11 died before one year of age. Among survivors, six developed inflammatory manifestations after the age of two.

Twenty-seven (80%) patients received immunosuppressive therapy, including glucocorticosteroids (n=25), IL-1R antagonist (n=6), and JAK1/2 inhibition (n=5). Six patients underwent HSCT, of whom four survived (one 12 years post-transplant, three at 1-year follow-up post-HSCT). Other two patients required lung transplantation.

ZNFX1 deficiency is characterized by a broad phenotypic spectrum ranging from severe, early-onset HLH to milder, later-onset disease. Targeted therapies and HSCT showed benefit in selected patients. Further studies are needed to define optimal management and long-term outcomes.

Peptide amphiphiles (PAs) are supramolecular biomaterials that self-assemble into nanofibrous networks resembling natural matrix components and can modulate the immune microenvironment during tissue repair. We investigated the immunomodulatory properties of a glutamic acid-based PA (PA-E3) and 2 variants, TGF-β1-binding PA-T3 and BMP-2-binding PA-B3. Hydrogels were exposed to peripheral blood mononuclear cells (PBMCs). After 48 hours, PBMC viability and spontaneous proliferation were evaluated together with anti-CD3 and anti-CD28 mAb-stimulated proliferation of CD4⁺ T cells, CD8⁺ T cells, and CD19⁺ B cells. Mechanistic insights were obtained by RNA-seq. Both functionalized PAs were biocompatible, with viability and spontaneous proliferation statistically indistinguishable from PA-E3. PA-E3, PA-T3, and PA-B3 induced comparable suppression in stimulated PBMCs, indicating that this reflects a shared property of the scaffold and that PA-T3 and PA-B3 do not confer additional immunosuppressive activity. Transcriptomic profiling showed that PA-B3 induced minimal transcriptional alterations, with 47 differentially expressed genes, whereas PA-T3 elicited a broader response involving 366 genes. Pathway enrichment indicated that PA-T3 modulates chemotaxis, leukocyte migration, angiogenesis, inflammatory response regulation, fibrinolysis, extrinsic apoptotic signaling, cell-cell adhesion, leukocyte proliferation, and ossification. These findings highlight the selective immune-regulatory potential of PA-T3 and support epitope-specific PAs as immune-instructive scaffolds for bone repair.

Introduction and aim: Intravital imaging has produced a rich immune map of cell behavior in native tissues, yet extracting biological meaning remains a bottleneck. Two computational strategies dominate. Track-based analysis relies on centroid detection per frame and yields kinematic parameters (speed, directionality), but is time-consuming, error-prone and blind to shape and context. Morphological analysis, implemented in Cecelia, segments cell contours frame-by-frame and captures shape dynamics, yet still treats cells as isolated entities. Neither exploits the information carried by interactions with other cells or structures such as collagen fibers. We introduce a third, interaction-aware layer based on graph neural networks (GNNs), benchmarked on T cell–dendritic cell (DC) encounters.

Design and methods: 2-photon intravital movies of lymph node T cell–DC interactions were processed in Cecelia to obtain (i) tracks, (ii) per-frame morphological features, and (iii) spatial graphs encoding T cell–DC and T cell–collagen neighborhoods. Behavioral states were extracted in each modality via unsupervised clustering of actions.

Results: Track- and morphology-based clustering recovered overlapping but incomplete behavioral repertoires. GNN-based analysis additionally resolved engagement, scanning and detachment states tied to DC contact and fiber alignment, refining the action landscape.

Conclusions: Interaction-aware GNN analysis complements tracking and morphology, offering a richer, context-sensitive immune map of T cell–DC behavior.

Shellfish is one of the "big nine" food allergens, accounting for over 90% of reported food allergy cases globally. This allergen particularly impacts Southeast Asian countries such as Indonesia, the Philippines, and Thailand, which are among the highest seafood consumers worldwide. Accurate and comprehensive data on the prevalence of shellfish allergy and sensitization are essential for effective allergy management and understanding geographic variations in allergic disease burden.

This systematic review aims to estimate the prevalence of shellfish allergy and sensitization in both the general and food-allergic populations across Southeast Asia and explore variations by country. A comprehensive search of multiple databases was conducted to identify relevant studies. Eligibility criteria, data extraction procedures, and quality assessment frameworks were predefined to evaluate methodological rigor, including clarity of research questions, study design, sample size, and validity. Data from included studies will be summarized using descriptive and narrative synthesis, and where appropriate, meta-analysis will be conducted to estimate pooled prevalence rates.

This review will provide critical insights into the epidemiology of shellfish allergy in Southeast Asia, supporting public health planning and identifying research gaps.

Introduction. Finkelstein–Seidlmayer vasculitis (acute hemorrhagic edema) presents with a distinctive phenotype of purpura and edema in a well-appearing child. Its features and pathogenesis remain poorly characterized. Methods. To further elucidate this condition, our Italo-Swiss Acute Hemorrhagic Edema Study Group compiled a database of all 599 published cases since 1913 and performed a detailed analysis. Results. Our studies (available on request) characterized the condition as follows: it typically affects children aged 4 weeks to 24 months and presents with abrupt-onset annular or nummular purpura and inflammatory edema. It is frequently preceded by a benign infection or vaccination, remains skin-limited in 90% of cases, and resolves spontaneously within three weeks without recurrences. Autoimmune markers (ANA, ANCA, rheumatoid factor, complement C3 and C4) are generally negative. Histology shows leukocytoclastic vasculitis, with absence of IgA deposition in most cases. Discussion Finkelstein–Seidlmayer vasculitis represents a model of self-limited small-vessel vasculitis, likely driven by transient immune complex–associated inflammation with predominant innate immune activation, without evidence of persistent adaptive autoimmunity. The absence of recurrence and serological abnormalities suggests a tightly regulated inflammatory response with intrinsic termination mechanisms. This condition provides a unique human model to investigate pathways of immune resolution, with potential implications for understanding and modulating chronic inflammatory and vasculitic diseases.

The heterotrimeric translocon Sec61 plays a central role in endoplasmic reticulum (ER) function by mediating the translocation of newly synthesized proteins into the ER lumen and facilitating the retrotranslocation of misfolded proteins for proteasomal degradation, a process known as ER-associated degradation (ERAD). Peptides presented on MHC-I molecules originate from proteasomal degradation, suggesting that inhibiting Sec61 could impact MHC-I peptide presentation. Kezar Life Sciences has developed two Sec61 inhibitors, KZR-261 and KZR-834, both of which exhibit broad antitumor activity in vitro and in vivo. In this study, KZR-834 was evaluated for its impact on MHC-I presentation, focusing on its effects on bulk MHC-I surface expression at non-toxic concentrations as well as on the presentation of selected
MHC-I peptides. Flow cytometric analysis revealed a concentration-dependent reduction in MHC-I surface expression in MC57 cells. Notably, the effects of KZR-834 extended to other, unrelated surface proteins, indicating a broader disruption of protein surface expression. Consistent with these findings, antigen presentation assays demonstrated diminished presentation of specific MHC-I peptides. To assess the in vivo consequences of Sec61 inhibition on immune function, antiviral immune responses were examined following Lymphocytic Choriomeningitis Virus (LCMV) infection. Treatment with KZR-834 impaired immune cell responses and led to a reduction in LCMV-specific CTLs.

Natural killer (NK) cells are pivotal in xenograft rejection, targeting porcine endothelial cells. CD47 acts as a “don’t eat me” signal by binding to signal regulatory protein alpha (SIRPα), thereby suppressing immune activation. While this axis has been well characterized in macrophages, its influence on NK cell-mediated xenograft rejection is less understood. We investigated whether expression of human CD47 (hCD47) on porcine aortic endothelial cells (PAECs) from transgenic pigs inhibits human NK activity. Using static cultures and microfluidic systems to simulate physiological conditions, we found that hCD47 expression on PAECs significantly impaired direct NK cytotoxicity. Under flow, NK cell migration[GP1] across hCD47-expressing PAECs was significantly reduced compared with WT PAECs. However, when heat-inactivated human plasma (containing anti-pig non-αGal antibodies) was added, hCD47 expression did not protect αGal-knockout PAECs from NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Single-cell RNA sequencing overall homogeneous NK subtype distribution between WT and hCD47-expressing PAEC conditions. However, a small set of differentially expressed genes showed increased inhibitory receptor expression and reduced effector, activation, and proliferation signatures in NK cells exposed to hCD47. These findings identify hCD47 as an effective checkpoint against direct NK cytotoxicity, but insufficient to prevent ADCC, underscoring the need for combinatorial strategies to achieve durable protection from NK-driven xenograft rejection.

Introduction and aim
Central nervous system (CNS) involvement in systemic sarcoidosis is uncommon but associated with significant morbidity and therapeutic challenges. Treatment mainly relies on corticosteroids and immunosuppressive agents or biologics, while targeted therapies remain limited. Dysregulation of the JAK–STAT pathway has been implicated in sarcoidosis, supporting a rationale for JAK inhibition in refractory disease. The aim of this report was to evaluate JAK inhibition in multisystem sarcoidosis with CNS involvement.

Methods
We report a 51-year-old woman with multisystem sarcoidosis involving the lungs, lymph nodes, and CNS. Neurological features included central vertigo, gaze-evoked nystagmus, and gait ataxia. Work-up included brain and spinal MRI, whole-body PET/CT, pulmonary function tests, and clinical evaluation. After an initial course of high-dose corticosteroids, upadacitinib was initiated. Clinical, radiological, and laboratory data were collected.

Results
During treatment with upadacitinib 30 mg/day, MRI showed stable supra- and infratentorial white matter lesions without enhancement or signs of inflammation. After 13.4 months, partial regression of a thoracic spinal cord lesion was observed, with no new CNS lesions. PET/CT showed complete metabolic regression of pulmonary and lymph nodal disease. Neurological symptoms remained stable, and pulmonary function was preserved.

Conclusions
JAK inhibition may be a promising option in multisystem sarcoidosis with CNS involvement. Further studies are needed to confirm its efficacy and safety.

Introduction:
IgE is a central effector molecule in allergic disease. We previously demonstrated that immunization-induced anti-IgE antibodies can regulate IgE receptor targeting and effector function, supporting a physiological role for natural anti-IgE antibodies in controlling IgE responses. Here, we aimed to investigate the endogenous IgE–anti-IgE network in humans.

Methods:
Human IgE network parameters, including total IgE, anti-IgE antibodies, and IgE–IgG immune complexes (ICs), were analyzed longitudinally in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) treated with dupilumab and integrated with serum proteomics and clinical outcomes.

Results:
Free and IgG-complexed IgE segregated along distinct immunologic axes. Free IgE associated with type 2 inflammatory signatures, whereas IgE–IgG ICs associated with adaptive immune activation and reduced mast cell activation. During IL-4Rα blockade, total IgE declined while IgE–IgG ICs persisted or increased, resulting in enrichment of complexed relative to free IgE.

Conclusions:
These findings identify IgG-complexed IgE as a distinct natural IgE compartment associated with differential inflammatory programs. Together, our data support the concept that the IgE–anti-IgE network represents a physiological regulatory layer of allergic immunity.

Omalizumab-facilitated multi-allergen oral immunotherapy (OIT) desensitizes patients with multiple food allergies, yet mechanisms of cashew desensitization remain unclear. We investigated targeted and proteomic changes linked to cashew tolerance by comparing pre- and post-OIT samples from 22 desensitized participants in a phase 2 trial. The protocol combined omalizumab (weeks 1-16) with dose-escalation OIT (weeks 8-30). Matched plasma samples at baseline and week 52 were analyzed using targeted 250-plex NULISA and untargeted LC-MS/MS. Data analysis included variance partitioning, paired statistics, and XGBoost with SHAP. Exploratory analysis identified sex as the main driver of variance, requiring stratified analysis. In females, targeted profiling revealed attenuated Th2 inflammation, with decreased IL-4, CXCL8, and TGF-β1 and increased IL-36A. Machine learning analysis of untargeted proteomics data identified ENO1 and S100A9 as top predictors of post-treatment. In males, response centered on metabolic regulation and tissue remodeling, with increased FGF19, FGF21, and MMP3. Machine learning analysis of untargeted proteomics data identified AADAT and VASN as top predictors. Males also showed distinct B-cell changes, with reduced CXCL13 and increased TNFSF11 (RANKL). Omalizumab-facilitated OIT induces sexually dimorphic immunomodulation during cashew desensitization. Females display classical inflammation suppression, whereas males undergo metabolic and structural remodeling. Dual-proteomics identified sex-specific biomarkers supporting sex-stratified monitoring strategies.

Introduction

Immune-mediated diseases are traditionally classified as distinct clinical entities, yet they may share common upstream inflammatory pathways, leading to sometimes unexpected systemic interactions. Thymic stromal lymphopoietin (TSLP) is a key alarmin in type 2 inflammation and increasingly recognized as a systemic immune regulator.

Aim

Based on a clinical case of concomitant asthma and osteoarthritis responding to TSLP blockade, we explore potential mechanistic interactions.

Methods and Design

Case report of a 39-year-old woman with severe uncontrolled asthma and active treatment-refractory inflammatory osteoarthritis. Clinical course, MRI findings and a pain diary were analyzed before and after initiation of the anti-TSLP antibody tezepelumab. Literature review of preclinical and translational evidence explored potential connections.

Results and Conclusion

In our case study, tezepelumab led to rapid asthma control and, with delayed onset, to an unexpected marked improvement of the chronic lumbar pain. Symptom relief was dependent on injection interval and dose. Follow-up MRI showed reduced inflammatory changes. This observation suggests a potential role of TSLP-driven inflammation beyond classical type 2 diseases and supports the concept of shared upstream immune pathways across distinct clinical entities. Epidemiological and genetic association studies support a link between Th2 diseases and osteoarthritis, and experiments in mouse-models suggest a TSLP-driven phenotype in articular pathology. We discuss the available evidence exploring this potential interaction.

Atopic dermatitis (AD) frequently co-occurs with food allergy (FA), affecting 24% of adult AD patients. While gut barrier dysfunction is linked to FA pathogenesis, direct tissue-level evidence of intestinal involvement in AD remains limited. We investigated duodenal immune remodeling and barrier dysfunction in AD, and whether features differ between AD, FA, and comorbid AD+FA. Duodenal biopsies from 23 adults (healthy controls n=6; AD n=5; FA n=9; AD+FA n=3) were analyzed by imaging mass cytometry for cellular composition, spatial organization, and intraepithelial lymphocyte density, and by NanoString transcriptomic profiling. All disease groups shared barrier damage, mucosal inflammation, and disturbed antigen presentation: increased epithelial cell spacing, expanded cytotoxic T cells and eosinophils, upregulated epithelial stress markers (XBP1, SOCS3), reduced MHC-II, and disrupted M1 macrophage–DC/NK co-localization. Disease specific patterns emerged: AD showed the highest cytotoxic T cell and M1 macrophage densities with transcriptomic signs of barrier repair (MUC2, MUC4, TFF3, claudins) alongside dampened innate sensing (reduced TLRs, MHC-II). FA exhibited active inflammatory priming (NLRP6 inflammasome, chemokines). AD+FA displayed pronounced type 2-skewed polarization (IL13, CCL2).AD patients exhibit duodenal immune remodeling and epithelial barrier dysfunction, supporting the gut-skin axis concept. Rather than a uniform type 2 driven pathology, each condition shows a distinct mucosal signature.

Background
Autoantibodies to GBM, MPO and PR3 are key diagnostic markers for anti-GBM disease and ANCA-associated vasculitides (AAV): MPA, GPA and EGPA. Conventional testing often relies on single-analyte assays, which may delay diagnosis and increase operational burden. We evaluated the analytical performance of a novel, fully automated multiplex microarray immunoassay (MosaiQ AiPlex^® VAS, AliveDx, Switzerland) intended for concurrent detection of IgG antibodies to PR3, MPO, and GBM as an aid in the identification of AAV and anti-GBM disease.

Methods
The investigational device was evaluated using de-identified sera, reactive or non-reactive for PR3, MPO, or GBM IgG antibodies. Analytical performance was assessed in comparison with a routine method (ALBIA: addressable laser bead immunoassay) by calculating the positive percent agreement (PPA) and negative percent agreement (NPA).

Results
Excluding equivocal results, PPA was 98.5% (64 of 65 samples, 95% CI: 91.7—100) for anti-GBM, 92.9% (224 of 241 samples, 95% CI: 88.9—95.8) for anti-MPO, and 91% (132 of 145 samples, 95% CI: 85.2—95.1) for anti-PR3. NPA was 97.6% (566 of 580 samples, 95% CI: 96—98.7) for anti-GBM, 97.5% (472 of 484 samples, 95% CI: 95.7—98.7) for anti-MPO, and 94.8% (560 of 591 samples, 95% CI: 92.6—96.4) for anti-PR3.

Conclusion
The investigational multiplexed microarray immunoassay showed high analytical concordance with ALBIA, offering an efficient alternative for the concurrent serologic evaluation of PR3, MPO, and GBM antibodies, supporting its utility in the diagnostic workup of AAV and anti-GBM disease.

Introduction/Aim of the Study: Atopic dermatitis (AD) chronicity is sustained not only by effector cytokines, but also by co-stimulatory pathways that maintain T-cell activation and memory. The OX40/OX40L axis has emerged as a relevant contributor to these processes in AD [1-3]. We reviewed its role in AD pathogenesis and the rationale for therapeutic blockade.

Design and Methods: A narrative review of recent preclinical and clinical literature on the OX40/OX40L axis in AD was performed, focusing on immunopathogenesis and therapeutic relevance.

Results: OX40/OX40L signaling is upregulated in AD lesional skin and may contribute to disease chronicity through interconnected mechanisms [1-3]. TSLP released by damaged keratinocytes induces OX40L expression on dendritic cells, promoting OX40-dependent T-cell priming and Th2 polarization [4,5]. This interaction activates NF-κB and PI3K-AKT signaling, supporting the persistence of multiple inflammatory T-cell subsets, including Th2, Th1, Th17, and Th22 [3,6]. OX40 signaling also impairs Treg function by reducing IL-10 production [1,7] and promotes the survival of activated T cells through upregulation of anti-apoptotic molecules such as Bcl-2 and Bcl-xL [3,8]. These findings help explain persistent inflammation and recurrent flares in AD. Early clinical data support this pathway as a therapeutic target.

Conclusions: The OX40/OX40L axis links innate immune activation, Th2 polarization, impaired immune regulation, and memory persistence in AD. This supports the biologic relevance of the pathway in chronic and relapsing AD.

Background: Diagnostic marker of autoimmune hepatitis (AIH) type 1 are antinuclear antibodies (ANA). We characterized ANA patterns and specific autoantibodies in pediatric AIH (pAIH) patients to identify ANA-associated disease entities that may have therapeutic or prognostic relevance.

Methods: We performed centralized serological analysis of serum samples from the Swiss Autoimmune Liver Disease Cohort Study (AILD). ANA titers and patterns were assessed, and specific autoantibodies were characterized in patients with pAIH onset (age <18 years).

Results: We analyzed 21 samples with previously reported positive ANA titers; in centralized testing 10 samples had titers ≥ 1:80 (positive) and 11 <1:80 (negative). Baseline characteristics including demographics, biochemistry at diagnosis, comorbidities, and treatment, did not differ between patients with positive and negative ANA titers. Likewise, no differences were observed in AILD-associated autoantibodies at diagnosis or at sampling time. A common ANA pattern was AC-4 followed by AC-1, often occurring in combination. The AC-1 pattern was mainly associated with anti-nucleosome and/or -histone autoantibodies, whereas AC-4 positive sera none of the two most common autoantibodies, TROVE-2 (Ro-60) and LA (SS-B), were detected.

Conclusion: Results suggests that ANA-titer, -pattern, and the few confirmed autoantibodies (anti-histone, anti-nucleosome) have no correlation with biochemistry markers and no relevance in therapy decision. Isolated evaluation of ANA titers and patterns in this context may not be clinically conclusive.

Introduction and aims: Central and peripheral immune tolerance limit autoimmunity mediated by self-reactive T cells, but tolerance to tumor-associated self-antigens can also constrain the efficacy of immunotherapies like cancer vaccines. Here, we investigated the antigen-specific T‑cell receptor (TCR) repertoire in mice who do and do not exhibit immune tolerance to the melanoma-associated antigen tyrosinase-related protein 2 (TRP2), both before and after immunization.

Design and methods: Using TRP2 knockout mice and heterozygous littermate controls, we investigated the same antigen as both a tumor-specific and a tumor-associated antigen.

Results: While the TCR repertoires in untreated mice were comparably diverse, immunization induced markedly greater expansion of TRP2-specific T cells, including the dominant clone, when TRP2 functioned as a tumor-specific antigen. TRP2-deficient mice also completely rejected established B16F10 melanomas after therapeutic vaccination and displayed a significantly larger population of stem-like tumor-infiltrating T cells.

Conclusions: These findings demonstrate that peripheral T‑cell tolerance is sufficient to prevent melanoma rejection after vaccination, despite minimal effects on overall TCR repertoire composition. Modulating the interplay between peripheral tolerance and antitumor immune responses may therefore increase the efficacy of cancer vaccines targeting self-antigens.

Background: Drug-induced autoimmune-like hepatitis (DI-ALH) mimics idiopathic autoimmune hepatitis but is triggered by specific pharmacological agents. We report a case of severe icteric DI-ALH with tibolone and diclofenac as possible triggers.

Case Presentation: A 62-year-old woman presented with jaundice, marked elevation of transaminases, bilirubin, alkaline phosphatase, and hypergammaglobulinemia, with positivity for ANA, ENA, anti-actin, and anti-dsDNA antibodies. Liver biopsy demonstrated lymphomononuclear portal inflammation without interface hepatitis or increased plasma cells, as well as acute lobular hepatitis with predominant zone 3 involvement, features of acute cholestasis, hepatocellular necrosis, and ballooning degeneration. The patient had received tibolone for 10 years and diclofenac in the months preceding symptom onset.

Methods: To discriminate between suspected agents, a cytokine-based lymphocyte transformation test (Cyto-LTT) was performed, assessing drug-specific T-cell activation by measuring interferon-γ and interleukin-5 release.

Results: Treatment with oral prednisone led to gradual biochemical improvement. Despite withdrawal of both drugs, corticosteroid therapy remains required. Progressive decline in autoantibody titers and IgG levels has been observed. Cyto-LTT results are pending.

Conclusion: This case underscores the diagnostic challenge of DI-ALH with multiple potential offending agents. Cyto-LTT may help identify the responsible drug and avoid hazardous re-exposure.

Background: Monitoring of hepatic sarcoidosis mainly relies on biochemical parameters, although clinical progression despite biochemical improvement has been observed. The role of liver elastography as a longitudinal marker of structural disease evolution remains unclear. We assessed the relationship between biochemical response, liver stiffness, and disease evolution.

Methods: We conducted a retrospective single-center cohort study of patients with hepatic sarcoidosis. Biochemical response was categorized as complete, partial, absent, or worsening. Structural disease evolution was assessed by longitudinal liver elastography measurements. Clinical progression was defined using a composite clinical endpoint.

Results: Twenty-two patients were included with a median follow-up of 9 years (IQR 3.5–14.8). Nineteen patients (86%) achieved a complete or partial biochemical response. Biochemical improvement was generally associated with decreasing liver stiffness, whereas biochemical non-response was associated with increasing liver stiffness. All patients with worsening liver stiffness experienced clinical disease progression, while all patients with improving liver stiffness remained clinically stable. Notably, two patients (9%) showed biochemical improvement despite progressive structural liver disease.

Conclusion: Biochemical response correlates with structural improvement in most patients with hepatic sarcoidosis but does not fully capture disease evolution. Longitudinal liver elastography may add value for disease monitoring and treatment decisions.

Introduction and Aim: Fibrosis-6 (FIB-6) is a non-invasive diagnostic index derived from routine laboratory parameters and developed using machine learning with a random forests algorithm to predict hepatic fibrosis stage. It has been validated in chronic liver disease related to hepatitis C, hepatitis B, and metabolic dysfunction-associated fatty liver disease. This study aimed to validate FIB-6 in patients with autoimmune hepatitis (AIH).

Materials and Methods: The performance of FIB-6 was evaluated in 217 patients with confirmed AIH from Egypt (n=87), Saudi Arabia (n=52), and Greece (n=78). Liver biopsy samples were scored by experienced pathologists using the METAVIR system. Results were compared with FIB-4, APRI, and AAR.

Results: FIB-6 showed high sensitivity and negative predictive value (NPV) for excluding advanced fibrosis and cirrhosis, but limited specificity. For cirrhosis, sensitivity, specificity, PPV, and NPV were 91.7%, 22.9%, 31.3%, and 87.8%, respectively. For advanced fibrosis (F3-4), values were 94.6%, 17.0%, 54.4%, and 75.0%, respectively. For significant fibrosis (F2-4), values were 93.5%, 9.4%, 70.6%, and 33.3%, respectively. Compared with FIB-4, APRI, and AAR, FIB-6 achieved the highest sensitivity and NPV for ruling out severe fibrosis and cirrhosis (98.2% and 80.0% vs. 74.8% and 61.1%, 74.8% and 61.6%, and 57.7% and 60.2%, respectively).

Conclusion: FIB-6 is a simple, non-invasive tool with high sensitivity and NPV, making it useful for ruling out advanced fibrosis and cirrhosis in AIH patients. Further validation in larger cohorts is recommended.

Background: MRGPRX4 is a bile acid- and heme metabolite-sensing receptor expressed in peptidergic sensory neurons of dorsal root and trigeminal ganglia. It has emerged as a mediator of hepatobiliary pruritus, a debilitating symptom with limited therapeutic options, yet its pharmacology remains poorly characterized and selective antagonists are lacking.

Methods: Natural product and pharmacological compound libraries were screened for MRGPRX4 ligands using β-arrestin recruitment assays (PathHunter, DiscoverX) at 10 μM. Concentration–response studies determined EC₅₀ or IC₅₀ values.

Results: Novel agonists included dioscin (EC₅₀: 3.83 μM), echinocystic acid (4.17 μM), sophoraflavanone G (5.93 μM) and18-β-glycyrrhetinic acid (11.2 μM). FXR agonists cilofexor (52.1 μM), tropifexor (19.4 μM) and obeticholic acid (23.1 μM) also activated MRGPRX4. Antagonists included psoralidin (0.608 μM), disulfiram (1.50 μM), flavonol (2.82 μM) and berbamine (IC₅₀: 5.16 μM). Clinically used PPAR agonists also inhibited MRGPRX4, including bezafibrate (79.6 μM), elafibranor (23.2 μM), fenofibrate (2.77 μM) and seladelpar (2.25 μM).

Conclusions: Structurally diverse MRGPRX4 agonists and antagonists were identified. FXR agonist-mediated activation may contribute to hepatobiliary itch, whereas inhibition by PPAR agonists may underlie antipruritic effects and therapeutic repurposing opportunities. These findings support further investigation into MRGPRX4 signalling and targeted antipruritic therapy development in hepatobiliary pruritus.

Background: The gut microbiome is essential for intestinal barrier integrity and immune homeostasis, yet the direct effects of food additives on microbial growth and function remain unclear. We assessed the impact of common additives on human fecal microbiome dynamics under anaerobic conditions.

Methods: Fecal microbiota from healthy donors were cultured with graded concentrations of monosodium glutamate (MSG), maltol, and ethyl maltol. Growth was monitored by OD600 over 48 h. Selected conditions were analyzed by shotgun metagenomics and SP3-based metaproteomics.

Results: MSG did not affect overall growth, whereas maltol and ethyl maltol inhibited growth in a dose-dependent manner within 12h. At the family level, MSG induced selective, sex-specific shifts (↓Oscillospiraceae, ↑Odoribacteraceae in males) without global disruption. Metaproteomics revealed functional reprogramming under MSG, characterized by enhanced glutamate metabolism (↑glutamate dehydrogenase, glutaminase, glutamyl-tRNA synthetase; ↓glutamine synthetase). In contrast, maltol and ethyl maltol caused stronger ecological effects, with high-dose maltol reducing key fermentative families, including Lachnospiraceae and Oscillospiraceae.

Conclusions: Food additives induce selective, compound-specific microbiome responses. MSG drives metabolic adaptation without affecting growth, while maltol-derived compounds exert stronger inhibitory and taxonomic effects, particularly on core fermentative taxa. These findings highlight subtle but functionally relevant microbiome restructuring.

Background
Anti–soluble liver antigen (anti-SLA) antibody is considered highly specific for autoimmune hepatitis (AIH), but its significance outside classical AIH remains uncertain. We report two patients with anti-SLA positivity without clinicopathological evidence of AIH.

Case presentation
A 56-year-old woman with mixed connective tissue disease treated with hydroxychloroquine showed persistent high-titer anti-SLA positivity (70–85 U/mL) and ANA positivity (1:5120), while liver enzymes and IgG remained normal. Transient elastography, abdominal ultrasound, and liver biopsy were unremarkable except for minimal steatosis. According to simplified IAIHG criteria, she did not meet criteria for probable or definite AIH. Liver tests and stiffness remained normal after 2 years.

A 75-year-old man with diffuse large B-cell lymphoma complicated by hemophagocytic lymphohistiocytosis developed acute cholestatic liver injury associated with transient anti-SLA and ANA positivity. Liver histology showed cirrhotic remodeling, inflammatory changes, and cholestasis, without characteristic features of AIH or lymphoma infiltrates, although hepatic involvement was suspected given the high PET/CT uptake. Viral hepatitis was excluded. After hematological treatment and resolution of systemic inflammation, anti-SLA became undetectable and cholestasis resolved.

Discussion and Conclusion
Anti-SLA positivity may rarely occur outside classical AIH, either as persistent isolated seropositivity in systemic autoimmunity or as transient positivity during profound immune dysregulation.

Background: Primary Biliary Cholangitis (PBC) has a variable natural history. The GLOBE and UK-PBC scores predict liver-related outcomes but regional diagnostic practices may influence disease stage at presentation. We compared clinical characteristics and predicted outcomes of Swiss PBC patients with the original GLOBE (n=2,488) and UK-PBC (n=1,916) derivation cohorts, hypothesizing that Swiss patients present at an earlier stage.

Methods: Retrospective analysis of Swiss PBC patients treated with UDCA. Baseline demographics, biochemical markers, and GLOBE/UK-PBC scores after 12 months of UDCA were compared against published derivation cohort data.

Results: In the GLOBE cohort (n=159), median age was 55.2 (47–64) years; 135 (85%) were female. Swiss patients had lower baseline ALP (1.3 [0.74–2.75] vs. 1.9 [1.2–3.5] × ULN) and higher platelet ratio (1.65 vs. 1.0). After 12 months of UDCA, ALP remained lower (1.2 [0.71–1.90] vs. 1.34 [0.93–2.26] × ULN). The median GLOBE score was 0.44 vs. 0.78–0.86 in the derivation cohort (p 0.05). In the UK-PBC cohort (n=115), median age was 50.3 (43–59) years; 108 (94%) were female. The UK-PBC 10-year risk of end-stage liver disease was 4.8% vs. 9–15% in the original cohorts.

Conclusion: Swiss PBC patients present at an earlier disease stage with more favorable prognostic profiles than the original international cohorts, suggesting that robust diagnostic pathways may facilitate earlier intervention and improved transplant-free survival.

Introduction and Aim

Chronic comorbidities, including hepatopathies, are increasingly recognized in pediatric cancer survivors, but their pathophysiology during long-term follow-up remains incompletely understood. This case highlights the challenges of investigating abnormal liver tests in this population.

Design and Methods

Case report of a 5-year-old boy with persistent mixed liver injury following chemotherapy for common acute lymphoblastic leukemia (c-ALL).

Results

A five-year-old boy with c-ALL was treated according to an ALL BFM 2015–analog protocol. Maintenance therapy included 6-mercaptopurine, methotrexate, and antimicrobial prophylaxis.

Following chemotherapy, persistent elevation of transaminases and gamma-glutamyl transferase (GGT) was observed. Extensive diagnostic workup was negative. Drug-induced hepatotoxicity was suspected; however, liver enzyme abnormalities persisted despite discontinuation of hepatotoxic agents.

Liver histology revealed mixed steatosis, hepatocellular ballooning, portal inflammatory infiltrates with interface activity, and porto-portal fibrosis. Seronegative autoimmune hepatitis (AIH) was suspected, and treatment with prednisolone followed by azathioprine resulted in progressive normalization of liver enzymes, supporting the diagnosis.

Conclusion

This case underscores the importance of monitoring for hepatic comorbidities in cancer survivors and highlights the challenges of distinguishing chemotherapy-related toxicity from autoimmune hepatitis in pediatric ALL survivors. A multidisciplinary approach is essential in managing this rare condition.