CXCL13 and CXCL9 CSF Levels in Central Nervous System Lymphoma—Diagnostic, Therapeutic, and Prognostic Relevance

Abstract

Background: Diagnostic delay and neurologic deterioration are still a problem for the treatment of rapidly progressing CNS lymphoma (CNSL); there is an unmet need for a diagnostic test with a high diagnostic yield and limited risk, minimizing the time to the initiation of effective treatment.Methods: In this prospective monocentric study, we analyzed the utility of CXCL13 and CXCL9 as diagnostic, therapeutic and prognostic biomarkers for CNSL. Cerebrospinal fluid (CSF) from 155 consecutive patients admitted with brain lesions of various origins was collected. Levels of CXCL13 and CXCL9 were analyzed by ELISA. Additionally, CSF was analyzed during CNSL disease course (relapse, remission, progress) in 17 patients.Results: CXCL13 and CXCL9 CSF levels were significantly increased in patients with CNSL compared to control patients with lesions of other origin. Using logistic regression and a minimal-p-value approach, a cut-off value of 80 pg/ml for CXCL13 shows high sensitivity (90.7%) and specificity (90.1%) for the diagnosis of active CNSL. CXCL9 at a cut-off value of 84 pg/ml is less sensitive (61.5%) and specific (87.1%). Both cytokines correlate with the clinical course and response to therapy.Conclusions: Our results confirm the excellent diagnostic potential of CXCL13 and introduce CXCL9 as a novel albeit less powerful marker for PCNSL.

Serum, but Not Saliva, CXCL13 Levels Associate With Infiltrating CXCL13+ Cells in the Minor Salivary Gland Lesions and Other Histologic Parameters in Patients With Sjögren’s Syndrome

“…In this context, the association of CXCL13 serum levels in pSS patients with clinical and laboratory markers of B cell activation, including rheumatoid factor, hypergammaglobulinemia, hypocomplementemia, and high disease activity was rather anticipated. Furthermore, elevated CXCL13 levels have been linked to prediction, presence, prognosis and/or therapeutic response of NHLs (47)(48)(49)(50)(51). Although our findings along with previous studies (27,29), indicate that CXCL13 serum levels in pSS patients may associate with high risk to develop NHL, all studies failed to register CXCL13 serum levels as an independent lymphoma predictor.…”

A systematic review of CSF biomarker discovery in neuro-oncology: A roadmap to standardization and clinical application

“…94,134,135 With respect to diagnostics, CXCL13 concentrations > 80-106 pg/mL have achieved sensitivities of 69.9%-90.7% and speci cities of 90.1%-92.7% for CNSL (Table 3). 94,134,135 CSF CXCL13 levels have also been correlated with response to therapy, 94 and higher CSF concentrations have been associated with poorer survival outcomes in CNSL patients. 135 IL-10.…”

“…133 In CSF, CXCL13 is elevated in newly diagnosed and recurrent PCNSL and SCNSL patients compared to those with other CNS malignancies (including BrM and HGG) and neuro-in ammatory and infectious pathologies (Table S9). 94,134,135 With respect to diagnostics, CXCL13 concentrations > 80-106 pg/mL have achieved sensitivities of 69.9%-90.7% and speci cities of 90.1%-92.7% for CNSL (Table 3). 94,134,135 CSF CXCL13 levels have also been correlated with response to therapy, 94 and higher CSF concentrations have been associated with poorer survival outcomes in CNSL patients.…”

Progress of radiological‑pathological workflows in the differential diagnosis between primary central nervous system lymphoma and high‑grade glioma (Review)

“…VSIG4 is a phagocytic receptor that negatively regulates T-cell proliferation and IL-2 production (71). All these proteins may be upregulated in the CSF of patients with PCNSL compared with patients with GBM (71)(72)(73)(74)(75). The combination of different biomarkers can improve diagnostic performance.…”