Biomarker discovery using NUcleic Acid-Linked Immuno-Sandwich Assay in multiple sclerosis patients experiencing progression independent of relapse activity
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background/Objectives: This cohort study aimed to identify blood-based biomarkers associated with progression independent of relapse activity (PIRA) in persons with multiple sclerosis (pwMS) using the multiplex NUcleic Acid-Linked Immuno-Sandwich Assay (NULISA). Methods: NULISA ‘CNS Disease Panel’ and ‘Inflammation Panel’ were applied on plasma samples from pwMS following B cell-depleting therapy (BCDT; n = 185) or fingolimod ( n = 200), median follow-up 4.0 (BCDT) and 9.1 (fingolimod) years. Plasma NULISA results (322 unique proteins; 0.9 and 1 year after treatment start, respectively) were investigated for their potential to prognosticate PIRA. Results: ‘CNS Disease Panel’ derived glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were identified as predictive of PIRA by multivariable Cox regression models (GFAP: BCDT: hazard ratio (HR) = 1.79, 95% confidence interval (CI) = 1.26–2.55, p = 0.0011; fingolimod: HR = 1.73, 95% CI = 1.14–2.64, p = 0.0104; NfL: BCDT: HR = 1.99, 95% CI = 1.31–3.02, p = 0.0013). GFAP derived from the ‘Inflammation Panel’ exhibited patterns like those observed with ‘CNS Disease Panel’ derived GFAP. Beyond GFAP and NfL, 12 biomarker candidates predictive of PIRA were identified. No target passed multiple test corrections, but GFAP consistently showed the highest hazard. Conclusion: Among over 300 proteins investigated by NULISA, GFAP was the main biomarker significantly associated with future PIRA risk in our cohort.
Source: Multiple Sclerosis Journal
Authors: Sofia Sandgren, Aleksandra Maleska Maceski, Pascal Benkert, Maximilian Einsiedler, Sabine Schaedelin, Johanna Oechtering, Lutz Achtnichts, Patrice H Lalive, Stefanie Müller, Caroline Pot, Amanda Heslegrave, David Hunt, Jan Lycke, Robert Hoepner, Patrick Roth, Claudio Gobbi, Manuel Comabella, Tobias Derfuss, Ludwig Kappos, Cristina Granziera, Ahmed Abdelhak, David Leppert, Eline AJ Willemse, Henrik Zetterberg, Jens Kuhle
Institutions: Sahlgrenska University Hospital, Region Västra Götaland, University of Gothenburg, University of Basel, University Hospital of Basel, Kantonsspital Aarau, University of Geneva, University Hospital of Geneva, University of St.Gallen, Kantonsspital St. Gallen, Centre Hospitalier Universitaire Vaudois, University of Lausanne, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London, University of Edinburgh, University of Bern, University Hospital of Bern, University of Zurich, University Hospital Zurich, Università della Svizzera italiana, Universitat Autònoma de Barcelona, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Centre d'Esclerosi Múltiple de Catalunya, University of California, San Francisco, University of Wisconsin–Madison
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,400
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Universität Basel, Stiftelsen för Gamla Tjänarinnor, International Progressive MS Alliance, National Institute for Health and Care Research, Multiple Sclerosis Society, University College London, European Commission, National Research Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Svenska Forskningsrådet Formas, Hjärnfonden, Vetenskapsrådet, Göteborgs Läkaresällskap, Svenska Läkaresällskapet, UK Dementia Research Institute, Olav Thon Stiftelsen, HORIZON EUROPE Framework Programme
Awards: G1057200632, G1307999793, G1343867371, G1451607819, G150733400, G1546555014, G1551449788, G1802301745, G1833008592, G1928552717, G1938858119, G196098375, G2081597990, G2083948481, G2224941001, G2434909840, G2475953241, G2543812357, G2799940023, G2804859505, G292763017, G3029915786, Fluid biomarkers for neurodegenerative dementias, G3384306495, G3809224024, G3903502641, G3914690605, G4166693258, G4234328627, G4244943609, G4260843567, G432431387, G4377393254, G4663484487, G4786159458, G4960203590, G5040492720, G506008078, G516766298, G5264190596, Fluid biomarkers for neurodegenerative dementias, G5576250680, G5712520100, G5778058681, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6158734006, G6207287561, G6361952146, G6544145387, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6701856265, G6745400708, G691317373, G7075164165, G7293611571, G7972240148, G8782684654
OpenAlex ID: W4415150296