CD138 as a Specific CSF Biomarker of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The aim of this study was to identify novel biomarkers for multiple sclerosis (MS) diagnosis and prognosis, addressing the critical need for specific and prognostically valuable markers in the field. METHODS: We conducted an extensive proteomic investigation, combining analysis of (1) CSF proteome from symptomatic controls, fast and slow converters after clinically isolated syndromes, and patients with relapsing-remitting MS (n = 10 per group) using label-free quantitative proteomics and (2) oligodendrocyte secretome changes under proinflammatory or proapoptotic conditions using stable isotope labeling by amino acids in cell culture. Proteins exhibiting differential abundance in both proteomic analyses were combined with other putative MS biomarkers, yielding a comprehensive list of 87 proteins that underwent quantification through parallel reaction monitoring (PRM) in a novel cohort, comprising symptomatic controls, inflammatory neurologic disease controls, and patients with MS at various disease stages (n = 10 per group). The 11 proteins that passed this qualification step were subjected to a new PRM assay within an expanded cohort comprising 158 patients with either MS at different disease stages or other inflammatory or noninflammatory neurologic disease controls. RESULTS: This study unveiled a promising biomarker signature for MS, including previously established candidates, such as chitinase 3-like protein 1, chitinase 3-like protein 2, chitotriosidase, immunoglobulin kappa chain region C, neutrophil gelatinase-associated lipocalin, and CD27. In addition, we identified novel markers, namely cat eye syndrome critical region protein 1 (adenosine deaminase 2, a therapeutic target in multiple sclerosis) and syndecan-1, a proteoglycan, also known as plasma cell surface marker CD138 and acting as chitinase 3-like protein 1 receptor implicated in inflammation and cancer signaling. CD138 exhibited good diagnostic accuracy in distinguishing MS from inflammatory neurologic disorders (area under the curve [AUC] = 0.85, CI 0.75-0.95). CD138 immunostaining was also observed in the brains of patients with MS and cultured oligodendrocyte precursor cells but was absent in astrocytes. DISCUSSION: These findings identify CD138 as a specific CSF biomarker for MS and suggest the selective activation of the chitinase 3-like protein 1/CD138 pathway within the oligodendrocyte lineage in MS. They offer promising prospects for improving MS diagnosis and prognosis by providing much-needed specificity and clinical utility. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CD138 distinguishes multiple sclerosis from other inflammatory neurologic disorders with an AUC of 0.85 (95% CI 0.75-0.95).

Cerebrospinal fluid chitinase-3-like protein 1 level is not an independent predictive factor for the risk of clinical conversion in radiologically isolated syndrome.

BACKGROUND: Younger age, male sex and presence of spinal cord lesion(s) increase the risk of conversion from radiologically isolated syndrome (RIS) to relapsing-remitting multiple sclerosis (RRMS). Elevated cerebrospinal fluid (CSF) chitinase-3-like protein 1 (CHI3L1) levels predict conversion from clinically isolated syndrome (CIS) to RRMS. OBJECTIVE: To evaluate the prognostic value of CSF CHI3L1 in RIS patients for conversion to RRMS. METHODS: We compared CSF CHI3L1 concentrations in RIS, CIS, RRMS and symptomatic controls (SCs). We analysed the influence of epidemiological, radiological and CSF parameters on the risk of clinical event. RESULTS: A total of 211 patients (71 RIS, 48 CIS, 50 RRMS and 42 SC) were included. CSF CHI3L1 levels were lower in RIS than in RRMS and higher in RIS with positive CSF versus negative CSF and SC. The presence of at least one spinal cord lesion was the only independent predictor of faster conversion to RRMS. Association of high CSF CHI3L1 levels, positive CSF (presence of oligoclonal bands and/or an elevated IgG index) or four Barkhof criteria with any spinal cord lesion showed a tendency for reduced mean conversion time. CONCLUSION: CSF CHI3L1 correlates with positive CSF but is not an independent predictor of the risk of conversion from RIS to RRMS.