Serum Glial-Related Biomarkers Show Distinct Contributions to Radiologic and Clinical Outcomes in Early Multiple Sclerosis.

@article{comabella2026serum,
  title = {{Serum Glial-Related Biomarkers Show Distinct Contributions to Radiologic and Clinical Outcomes in Early Multiple Sclerosis.}},
  author = {Manuel Comabella and Luca Bollo and Nicolas Fissolo and Pascal Benkert and Ingrid Klass and Carmen Tur and Estibaliz Saez de Gordoa and Lucia Gutierrez and Cristina Auger and Jordi Rio and Jaume Sastre-Garriga and Mar Tintore and Jens Kuhle and Àlex Rovira and Xavier Montalban},
  journal = {Neurology(R) neuroimmunology \& neuroinflammation},
  year = {2026},
  month = oct,
  doi = {10.1212/nxi.0000000000200663},
  url = {https://europepmc.org/article/MED/42879711},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Serum Glial-Related Biomarkers Show Distinct Contributions to Radiologic and Clinical Outcomes in Early Multiple Sclerosis.
AU  - Manuel Comabella
AU  - Luca Bollo
AU  - Nicolas Fissolo
AU  - Pascal Benkert
AU  - Ingrid Klass
AU  - Carmen Tur
AU  - Estibaliz Saez de Gordoa
AU  - Lucia Gutierrez
AU  - Cristina Auger
AU  - Jordi Rio
AU  - Jaume Sastre-Garriga
AU  - Mar Tintore
AU  - Jens Kuhle
AU  - Àlex Rovira
AU  - Xavier Montalban
PY  - 2026
DA  - 2026/10/14
JO  - Neurology(R) neuroimmunology & neuroinflammation
DO  - 10.1212/nxi.0000000000200663
UR  - https://europepmc.org/article/MED/42879711
AB  - Background and objectives  To investigate the association between serum levels of glial-related biomarkers, including glycoprotein nonmetastatic melanoma B (GPNMB), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), galectin-3, serpin peptidase inhibitor clade A member 3 (SERPINA3), chitotriosidase-1 (CHIT1), and chitinase 3-like 1 (CHI3L1) and 2 (CHI3L2), and the presence of paramagnetic rim lesions (PRLs) and the risk of progression independent of relapse activity (PIRA) in patients with a first demyelinating event.Methods  PRLs were identified using 3T susceptibility-based imaging. Univariable and multivariable linear regression models assessed the association between biomarker levels and the presence of PRLs at baseline. Univariable and multivariable Cox proportional hazards models investigated the association between biomarker levels and risk of PIRA during follow-up. sTREM2 and CHI3L1 levels were measured using single molecule array assays, whereas levels of the remaining biomarkers were determined using ELISA.Results  We included 135 patients (median age, 34.4 [interquartile range (IQR) 29.2-41.7] years; 98 [72.6%] women; median follow-up, 5.4 [IQR 2.7-9.4] years). PRLs were detected in 59 (43.7%) patients. The presence of ≥1 PRLs at baseline was associated with increased levels of CHI3L1 in univariable (multiplicative effect [ME] = 1.32; 95% CI 1.10-1.58; p = 0.003) and multivariable analyses (ME = 1.31; 95% CI 1.05-1.63; p = 0.01). Thirty (22.2%) patients developed PIRA during follow-up. Doubling of serum galectin-3 levels was associated with an increased risk of PIRA in univariable (hazard ratio [HR] = 1.76; 95% CI 1.06-2.94; p = 0.02) and multivariable analyses (HR = 2.15; 95% CI 1.22-3.80; p = 0.008). Similarly, doubling of serum CHI3L2 levels was associated with an increased risk of PIRA in both univariable (HR = 1.36; 95% CI 1.05-1.76; p = 0.02) and multivariable analyses (HR = 1.36; 95% CI 1.02-1.82; p = 0.03). The combined elevation of galectin-3 and CHI3L2 was associated with an increased risk of PIRA in multivariable analysis (HR = 8.44; 95% CI 3.01-23.70; p < 0.0001).Discussion  These findings suggest distinct contributions of glial-related biomarkers to radiologic and clinical outcomes in early multiple sclerosis. Validation in independent cohorts will be required before their value as blood prognostic biomarkers can be established.
SN  - 2332-7812
ER  -