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Facioscapulohumeral dystrophy (FSHD) is a debilitating neuromuscular disorder characterized by progressive muscle weakness, leading to significant morbidity. Despite its impact, approved therapies for FSHD are lacking, with only a handful of compounds in development. The urgent need for effective treatments underscores the importance of identifying biomarkers that correlate with disease activity or progression to facilitate clinical management and evaluate potential therapeutics for FSHD. Since inflammation plays a central role in FSHD pathophysiology, we are particularly interested in inflammatory biomarkers and have previously identified Interleukin-6 (IL-6) as a promising severity biomarker. To validate this hypothesis, we conducted two independent longitudinal studies: the CTRN-FSHD France (NCT04038138) and the Cytokine FSHD (NCT04694456), each enrolling 30 adult ambulant FSHD1 patients ((N=60, 53.2 ± 15.05 years, 53% men, age at onset 32.8 ± 16.1, D4Z4 repeat number 6.6 ± 0.2). Comprehensive clinical assessments, IL-6 measurements, and whole-body muscle Magnetic Resonance Imaging (MRI) scans were performed at baseline and after 12 months. We systematically investigated the association between IL-6 concentration and clinical as well as MRI data. Our results demonstrate a robust correlation between IL-6 levels and established clinical severity metrics (including Clinical Severity Score, Manual Muscle Testing sum score, 6-minute Walk Test, and Domain 1 of the Motor Function Measure-32 items) both at baseline and at the 12-month follow-up reaffirming IL-6 as a serum biomarker of FSHD severity. Furthermore, we observed a significant association between IL-6 levels and muscle composition, with higher IL-6 concentrations correlating positively with increased muscle fat infiltration and edema. This suggests a potential role for IL-6 in modulating muscle composition, possibly through its pro-inflammatory effects. Importantly, the longitudinal analysis revealed that changes in IL-6 levels over time positively correlate with changes in MRI composite scores, indicating a dynamic relationship between IL-6-mediated inflammation and the observed alterations in tissue structure or pathology detected by MRI. In conclusion, our findings not only confirm IL-6 as a reliable serum biomarker of FSHD severity but also highlight its close association with muscle composition changes. The observed correlation between IL-6 levels and MRI findings underscores the potential of IL-6 as a valuable tool for monitoring disease progression and evaluating treatment response in FSHD patients. [ABSTRACT FROM AUTHOR]

Context. In obesity, the infiltration of leukocytes into adipose tissue seems to play a key role in the development of inflammation and insulin resistance. Over-expression of adipophilin (ADPH) in adipose tissue, a protein which regulates lipid droplet structure and formation, has been reported in some studies. Objective. To investigate the role of ADPH 129-137 as a target for CD8+ T-cells in PBMCs of patients with obesity. Subjects and Methods. PBMCs were obtained from 9 non-diabetic obese patients and 11 healthy subjects expressing the HLA-A0201 molecule. The ELISPOT assay used to monitor the presence of IFN-γ producing CD8+ T-cells against a HLA class I-restricted epitope derived from Adipophilin (ADPH 129-137) and two control peptides: Flu MP58-66 and Melan-A27-35. Results. The outcomes showed no significant difference between patient group and healthy donors in response to ADPH 129-137. Conclusion. These results demonstrated that ADPH 129-137 peptide possibly does not act as an autoantigen in patients with obesity. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that choroid plexus (ChP) enlargement occurs in individuals with schizophrenia-spectrum disorders (SSD) and is associated with peripheral inflammation. However, it is unclear whether such an enlargement delineates a biologically defined subgroup of SSD. Moreover, it remains elusive how ChP is linked to brain regions associated with peripheral inflammation in SSD. A cross-sectional cohort of 132 individuals with SSD and 107 age-matched healthy controls (HC) underwent cerebral magnetic resonance imaging (MRI) and clinical phenotyping to investigate the ChP and associated regions. A case-control comparison of ChP volumes was conducted, and structural variance was analyzed by employing the variability ratio (VR). K-means clustering analysis was used to identify subgroups with distinct patterns of the ventricular system, and the clusters were compared in terms of demographic, clinical, and immunological measures. The relationship between ChP volumes and brain regions, previously associated with peripheral inflammation, was investigated. We did not find a significant enlargement of the ChP in SSD compared to HC but detected an increased VR of ChP and lateral ventricle volumes. Based on these regions, we identified 3 clusters with differences in cognitive measures and possibly inflammatory markers. Larger ChP volume was associated with higher volumes of hippocampus, putamen, and thalamus in SSD but not in HC. This study suggests that ChP variability, but not mean volume, is increased in individuals with SSD, compared to HC. Larger ChP volumes in SSD were associated with higher volumes of regions previously associated with peripheral inflammation., Competing Interests: Competing interests: The authors declare that they have no biomedical financial interests or potential conflicts of interest regarding the content of this report. A.H. received paid speakership by Janssen, Otsuka, Lundbeck, and Recordati and was member of advisory boards of these companies and Rovi. A.S. has been an honorary speaker for TAD Pharma and Roche and a member of advisory boards for Roche. P.F. received paid speakership by Boehringer-Ingelheim, Janssen, Otsuka, Lundbeck, Recordati, and Richter and was member of advisory boards of these companies and Rovi. S.P. received previous speaker fees and/or travel expenses from Novartis Pharma GmbH, Oertli AG, Bayer AG, Alcon Pharma GmbH, and Pharm-Allergan GmbH. EW was invited to advisory boards from Recordati, Teva and Boehringer Ingelheim. S.H. is supported by an Australian Research Training Program scholarship. D.S. is supported by an NHMRC Investigator Fellowship GNT 1194635. N.W. has received speaker fees from Otsuka, Lundbeck and Janssen. All other authors report no biomedical financial interests or potential conflicts of interest., (© 2024. The Author(s).)