Fatty liver disease is not just a liver problem.
It is a whole-body metabolic disease.

A major review by Prof. Norbert Stefan, Hannele Yki-Järvinen and Brent A. Neuschwander-Tetri shows that metabolic dysfunction-associated steatotic liver disease affects nearly 4 in 10 adults worldwide and most people with it do not die from liver failure, but from heart disease and cancer…

Important:

• Fatty liver comes in different types, driven by metabolism, fat distribution, or genetics
• The liver actively worsens blood sugar, cholesterol, and clotting risk
• Weight loss helps many…but not everyone responds the same way
• Some treatments improve liver health even without weight loss

The key message is simple:

One-size-fits-all medicine does not work for fatty liver disease!!!

Prevention, early detection and treatment need to focus on metabolic health across the whole body, not just liver enzymes…

If we treat fatty liver early, we also reduce diabetes, heart attacks and strokes later 🤞🏼

What should come first in routine care: liver screening, metabolic screening or both?

If useful, save, share or add your perspective below.

Read original review in The Lancet Group: https://lnkd.in/g3m4tA3k

#metabolichealth #fattyliver #cardiovascularhealth #prevention #publichealth

🔥Don't miss this #FeaturePaper by Moawiah Naffaa, PhD and Ola A. Al-Ewaidat.

Emerging AI- and Biomarker-Driven Precision Medicine in Autoimmune Rheumatic Diseases: From Diagnostics to Therapeutic Decision-Making


🔗More details: https://brnw.ch/21wY2dx


#OpenAccess #AutoimmuneRheumaticDiseases #ArtificialIntelligence #Biomarkers #DigitalHealth

Almost 40% of patients with fulminant herpes simplex virus hepatitis carry autoantibodies neutralizing type I interferons

🧬 Autoimmunity in the CAR era: from chronic suppression to immune reset
Autoimmune diseases affect close to 10% of the global population, and many patients still rely on life-long, non-selective immunosuppression with incomplete control and high toxicity. ⚠️🌍
A new Blood Reviews article on “CARing about autoimmune disorders” reframes CAR-based cell therapies as tools to actively reset immune tolerance, not just turn immunity “down” forever. 🔁🧠
🎯 Layer 1B-cell directed CAR-T as the backbone
CD19 CAR-T has become the leading strategy, inducing deep B-cell depletion and clinical remissions across SLE, IIM, MS, MG and SSc.🦋💪
BCMA CAR-T targets long-lived plasma cells and persistent autoantibodies in SLE, Sjögren’s syndrome and MG.🧫
Next-wave targets (CD20, CD22, CD70, BAFFR) aim for more selective depletion of pathogenic B- and plasma-cell subsets, with dual CD19/BCMA or CD20/BCMA CARs now in trials across multiple autoimmune indications.🌐📊
🧪 Layer 2 Precision tolerance: CAAR-T and CAR-Tregs
CAAR-T cells use the autoantigen as “bait” to delete only autoantigen-specific B cells (MuSK-CAART, pemphigus and others). 🎯
CAR-Tregs are engineered regulatory T cells that restore organ-specific tolerance without global B-cell ablation, with promising data in preclinical models of MS, T1D and vitiligo. 🧠🩺
Together, these platforms turn CARs into precision tolerance inducers rather than purely cytotoxic weapons.
🤖 Layer 3 – Expanding the cellular toolbox
The review maps an ecosystem of CAR platforms for autoimmunity: CAR-NK cells for off-the-shelf cytotoxicity, CAR-macrophages that rewire inflamed tissues, in vivo CAR-T that programs T cells directly in the patient, and allogeneic CRISPR-edited CAR-T products (such as BMS-986515) designed to avoid GVHD and rejection while achieving rapid, durable B-cell depletion. 🧬🧱
🌎 Trials & equity
Around 100 CAR-T/autoimmunity trials are registered worldwide. China and the US lead the field, while many regions remain under-represented, underscoring the need for global manufacturing and regulatory networks so immune reset is not restricted to a few countries. 🌍🤝
🚀 Take-home
CAR technology is emerging as a platform to recalibrate immune balance in autoimmunity and change the natural history of severe, refractory disease:
CD19 / BCMA / CD20 / CD22 / CD70 / BAFFR-directed CAR-T
CAAR-T for autoantigen-specific B cells
CAR-Tregs for organ-specific tolerance
CAR-NK and CAR-macrophages for innate re-programming
In vivo and allogeneic CAR-T for scalable, off-the-shelf access
From chronic immunosuppression to one-time or few-time immune reset with durable remission that is the horizon now opening for autoimmune patients. 🧬🔥
Doi: 10.1016/j.blre.2025.101354
#AutoimmuneDisease #CART #CAART #CARTreg #CARNK #CARMacrophages #CD19CAR #CD20CAR #CD22CAR #CD70CAR #InVivoCART #AllogeneicCART #ImmuneTolerance #SLE #MS #MyastheniaGravis #SystemicSclerosis #T1D #TranslationalImmunology #CellTherapy

🔍 Maladies auto-immunes : et si tout commençait dans vos intestins ? 🔍

Diabète de type 1, sclérose en plaques, polyarthrite rhumatoïde…

Et si ces maladies n’étaient pas uniquement liées à vos gènes ou à votre environnement, mais aussi à la façon dont votre intestin filtre (ou non) ce que vous mangez, respirez ou ressentez ?

Un concept révolutionnaire, longtemps négligé, bouscule aujourd’hui notre compréhension de l’auto-immunité : l’hyperperméabilité intestinale, aussi connue sous le nom de leaky gut.

🧱 L’intestin, votre première ligne de défense

Votre intestin n’est pas qu’un organe digestif.

C’est une frontière immunitaire stratégique : 70 % de vos cellules immunitaires y résident. Il décide de ce qui entre dans votre corps... ou pas.

Mais face à une vie moderne marquée par :
. une alimentation ultra-transformée,
. le stress chronique,
. les toxines environnementales,
. ou encore les infections persistantes…

Cette barrière se fragilise. Des molécules indésirables pénètrent, semant la confusion dans votre système immunitaire, qui peut alors… se retourner contre vous.

C’est ce dérèglement qui précède souvent l’apparition de nombreuses maladies auto-immunes, comme l’ont révélé plusieurs études scientifiques.

🧬 Zonuline : le messager qui ouvre (trop) les portes

Découverte par le Dr Fasano, la zonuline est une protéine qui module l’ouverture des jonctions serrées de votre intestin.

Quand elle est surproduite, ces jonctions s’ouvrent… trop. Résultat : des fragments alimentaires mal digérés, des toxines et même des bactéries peuvent s’infiltrer.

Ce n’est pas une conséquence de la maladie auto-immune.
C’est souvent un élément déclencheur.

🌱 Peut-on réparer l’intestin… et freiner l’auto-immunité ?

Contrairement à ce qu’on pense souvent, une maladie auto-immune n’est pas toujours irréversible.
Si la perméabilité intestinale en est un déclencheur, restaurer la barrière intestinale peut être une piste thérapeutique puissante.

🎯 Voici les 4 piliers pour agir dès maintenant :

1️⃣ Manger anti-inflammatoire : aliments bruts, riches en polyphénols, oméga 3, fibres, épices (curcuma, gingembre…).
2️⃣ Éliminer les agresseurs : gluten, produits ultra-transformés, sucres raffinés, additifs…
3️⃣ Apaiser le stress : cohérence cardiaque, méditation, sommeil réparateur…
4️⃣ Soutenir la muqueuse : L-glutamine, zinc, quercétine, collagène, probiotiques et prébiotiques sont vos alliés.

💡 Une approche fonctionnelle pour agir à la racine

En santé fonctionnelle, on ne masque pas les symptômes, on cherche les causes. Et souvent, elles résident dans l’interconnexion de vos systèmes internes.

💬 Et vous, avez-vous déjà exploré la piste intestinale pour comprendre vos symptômes auto-immuns ?

#SantéFonctionnelle #MaladieAutoImmune #Microbiote #LeakyGut #HyperPerméabilité

🔒 Disclaimer : Pour tout problème de santé, il est essentiel de consulter votre médecin. | 43 comments on LinkedIn

Epstein-Barr virus–mediated B cell reprogramming may initiate systemic lupus erythematosus

- Epstein-Barr virus (EBV) has been making waves as a candidate driver of diseases like multiple sclerosis and Long Covid. It has also long been linked to systemic lupus erythematosus (SLE), although the “why” behind this link has not been defined.

- Here, the authors provide evidence for a link between EBV infection and disease development using an original EBV sequencing (EBV-seq) approach, which combines EBV transcript detection with single-cell transcriptomics.

- The authors evaluated peripheral blood samples from 11 patients with SLE, finding a mean EBV+ B cell frequency of approximately 25 per 10,000 sequenced B cells. In contrast, EBV+ B cell frequencies ranged from 0 to 3 per 10,000 B cells in 10 healthy controls.

- By combining EBV-seq data with single-cell transcriptomics, the authors demonstrated that these latently infected EBV+ B cells were predominantly CD27+CD21low memory B cells exhibiting up-regulation of genes related to antigen processing and presentation, such as IFI30, TAP2, and PSMB6, a population not observed in EBV+ B cells from healthy controls.

- These EBV-infected B cells with antigen-presenting abilities had the capacity to activate autoreactive helper T cells, setting off a chain reaction where those T cells could activate other autoreactive B cells, including uninfected ones.

- These findings support a model in which extremely rare, but overpotent EBV+ “driver” B cells activate helper T cells, which then expand autoreactive EBV− B cells capable of generating the characteristic autoantibodies associated with SLE.

https://lnkd.in/eFGMi75V
https://lnkd.in/ew2DsivE

#lupus #immunology #autoimmunity #rheumatology

Decompensated cirrhosis describes an advanced clinical stage with clinical complications, such as ascites, variceal bleeding or hepatic encephalopathy, associated with considerable mortality. Portal hypertension is the main risk factor for developing decompensation in patients with compensated cirrhosis, whereas systemic inflammation is the key driving force for organ failure, that is, for acute-on-chronic liver failure in later stages of cirrhosis. As portal hypertension and systemic inflammation coexist in patients with cirrhosis, an improved understanding of their interaction and dynamic role in distinct stages of cirrhosis is an important step forward towards the development of urgently needed therapeutic interventions. Based on emerging evidence from clinical and translational studies, a novel concept of different predominant pathomechanisms of decompensated cirrhosis is presented, which includes portal hypertension-predominant, systemic inflammmation-predominant and mixed portal hypertension–systemic inflammation phenotypes. A comprehensive set of biomarkers and surrogates of portal hypertension and systemic inflammation might assist clinicians in identifying a predominance of one over the other cirrhosis phenotype. As survival rates of patients with decompensated cirrhosis have remained detrimental without liver transplantation over the past decades, future studies should build on this knowledge to develop effective portal hypertension and systemic inflammation-directed therapies for this underserved population. Portal hypertension and systemic inflammation are key factors driving decompensation and organ failure in cirrhosis. This Review examines those two factors and, based on their mechanistic interaction, proposes a new concept of the clinical phenotypes in decompensated cirrhosis.

The NEJM has just released the usual end-of-the-year list of most influential papers of 2025.

I found particularly amazing the paper and the editorial concerning allogeneic transplantation of CRISPR genetically-modified Beta cells for type 1 diabetes. A groundbreaking clinical observation that could revolutionise completely this deadly disease. More to come in 2026!

You can download it for free.

Autoantibody-triggered podocyte membrane budding drives autoimmune kidney disease

- Chronic kidney disease affects 1 in 10 people worldwide, with damage to specialized blood filter cells of the kidney, called podocytes, playing a critical role.

- In membranous nephropathy (MN), a major cause of nephrotic syndrome, circulating autoantibodies attack proteins on podocyte foot processes (FPs), damaging the kidney’s filtration barrier.

- This study shows that these autoantibodies trigger the formation of antigen-autoantibody aggregates on the podocyte FP plasma membrane.

- These aggregates bud off as stalked vesicles, termed autoimmunoglobulin-triggered extracellular vesicles (AIT-EVs), which are released into the urine.

- AIT-EVs carry disease-causing autoantibodies, their target antigens, essential FP proteins, and disease-associated stressors representing a mechanism for removing immune complexes (ICs) and waste. However, their excessive release leads to podocyte dysfunction and injury.

- The discovery of AIT-EVs bridges the gap between circulating autoantibodies and podocyte responses and can be harnessed in MN patients.

- Clinically, analysis of urinary AIT-EVs represents a novel non-invasive diagnostic tool to sensitively detect and monitor renal autoimmune activity in patients.

https://lnkd.in/ePD3_xDA

#autoimmunity #kidney #kidneydisease #biomarkers

Vitiligo is an acquired autoimmune depigmenting disorder that affects approximately 0.36% of the global population and presents in three forms based on lesion distribution: non-segmental, segmental and mixed vitiligo. Beyond its visible impact on the skin, vitiligo deeply affects mental well-being and quality of life. The pathogenesis of non-segmental vitiligo is influenced by genetic polymorphisms that are linked to immune response and melanogenesis pathways, whereas environmental factors contribute to disease onset. Diagnosis is generally clinical, with laboratory tests or biopsies rarely required. Melanocyte loss involves mechanisms, such as cellular stress, innate immune activation and adaptive immune responses, that specifically target melanocytes, with a central role for tissue-resident memory T cells. This cascade ultimately leads to the depletion of epidermal melanocytes and impairs melanocyte stem cell regeneration. Clinical management emphasizes shared decision-making with three primary objectives: halting depigmentation, initiating repigmentation and sustaining pigment restoration. Signs of active disease help clinicians to identify patients in need of intervention. Treatments approved in the past 2 years offer potential for reversing disease progression, and emerging therapies targeting key pathways to modulate immune activation and stimulate melanocyte regeneration and differentiation are being tested in clinical trials. Vitiligo is a chronic, autoimmune, depigmenting disorder that has both physiological and psychological effects on affected individuals. In this Primer, Seneschal and colleagues provide an overview of the epidemiology, pathogenesis, diagnosis and management of the condition as well as of its effect on quality of life, and highlight current and emerging treatments.

Read the Review now➡️
Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura
By Michael R. Snyder and Robert W. Maitta
Cited 3 times | Viewed 3406 times
Th

Encouraging to see the rapidly evolving translational landscape of CAR-T cell therapy in autoimmune diseases highlighted in Nature. The field is progressing from first-in-human studies in lupus toward phase I/II trials in rheumatoid arthritis, systemic sclerosis, and myositis - including our ongoing efforts at Charité. These developments point toward a potential shift from continuous immunosuppression to time-limited immune reset with the prospect of sustained, treatment-free remission.

Nature: “They don’t have symptoms”: CAR-T therapies send autoimmune diseases into remission
https://lnkd.in/dc2QEThC #AutoimmuneDiseases #Rheumatology #TranslationalMedicine #Immunotherapy

Interested in the Methodology of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria?

The Publication Series is Below:

Phase I/II Report: Generation and Reduction of Candidate Criteria (2021) - https://lnkd.in/eM_cbsME

Phase III-A/B Report: Defining and Structuring the Clinical and Laboratory Domains (2025) - https://lnkd.in/euGN5uFd

Phase III-C Report: Assessment of Patient Scenarios (Derivation Cohort) and Refinement of Definitions (2025) - https://lnkd.in/ezt258mf

Phase III-D Report: Multicriteria Decision Analysis (2024) - https://lnkd.in/eabvQvmN

The 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria (main paper, which includes the final criteria and phase IV validation report [2023]) - https://lnkd.in/eXnYY72D

Efforts to Better Characterize "Antiphospholipid Antibody Nephropathy" for the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria: Renal Pathology Subcommittee Report (2024) - https://lnkd.in/epbMZXvS

Medha Barbhaiya Stéphane ZUILY

Thank you to all the contributors.