CSF TACI and BAFF levels in patients with primary CNS lymphoma as novel diagnostic biomarkers

Mizutani, Hironori; Nakane, Shunya; Ikeda, Tokunori; Nakamura, Hideo; Takamatsu, Koutaro; Makino, Keishi; Tawara, Nozomu; Mukaino, Akihiro; Watari, Mari; Matsui, Hirotaka; Mukasa, Akitake; Ando, Yumiko

doi:10.1002/acn3.668

Cited by 8 publications

(7 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several other potential biomarkers for PCNSL have been identified in the past. The proteins neopterin [13], CXCL13 [11], IL-10 [9–12], IL-6 [9, 10, 12], β-microglobulin [10, 14], osteopontin [15], BAFF [30], sTACI and sBCMA [31], and sCD27 [16] have been analyzed for their potential as diagnostic biomarkers. Their reported sensitivities for the diagnosis of PCNSL ranged from 68% (ß2-microglobulin [14]) to 100% (sCD27 [16]) with specificities ranging from 63% (IL-6 [9]) to 100% (IL-10 [9]).…”

Section: Discussionmentioning

confidence: 99%

“…These factors include the study design, the composition of the control cohort (control patients with focal brain lesions of malignant, inflammatory, and infectious origin; control patients without focal lesions; healthy controls), the quantification method, the chosen cut-off level, and the number of patients included. For example, Mizutani et al recently present the value of BAFF and TACI as a biomarker for CNSL with a reported sensitivity and a specificity of 100% [30]. However, their retrospectively collected data included only nine PCNSL patients.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, increased APRIL expression in systemic B cell NHL correlates with lymphoma aggressiveness and inferior survival rate [29]. Recently, BAFF has also been implicated as a potential diagnostic biomarker in a small sample of PCNSL patients [30]. Also, two of its receptors, soluble TACI and soluble BCMA, are elevated in the CSF of PCNSL patients [31].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

APRIL and BAFF: novel biomarkers for central nervous system lymphoma

et al. 2019

View full text Add to dashboard Cite

Background Early diagnosis of CNS lymphoma (CNSL) is essential for successful therapy of this rapidly progressing brain tumor. However, in patients presenting with focal brain lesions, fast and reliable diagnosis of PCNSL remains a challenge. A proliferation-inducing ligand (APRIL) and B cell activating factor (BAFF) are important factors in the pathophysiology, diagnosis, and prognosis of systemic B cell malignancies. However, their utility as biomarkers for the diagnosis of CNSL and their effects on CNSL cells remain unclear. Methods In this prospective study, we analyzed the levels of APRIL and BAFF in the cerebrospinal fluid (CSF) of 116 patients with suspected focal brain lesions, including 53 CNSL patients. Additionally, we serially measured their levels during chemotherapy and relapse. Furthermore, we analyzed the effect of APRIL and BAFF on two B cell lymphoma cell lines using proliferation, viability, and chemotaxis assays. Results CSF levels of APRIL and BAFF reliably differentiated CNSL from other focal brain lesions (including primary and metastatic brain tumors, autoimmune-inflammatory lesions, and neuroinfectious lesions) with a specificity of 93.7% (APRIL, BAFF) and a sensitivity of 62.3% (APRIL) and 47.1% (BAFF). Serial CSF analysis of CNSL patients during chemotherapy and relapse demonstrates a close correlation of APRIL CSF levels and the course of this disease. In vitro, APRIL and BAFF showed anti-apoptotic effects during MTX treatment and mediated chemotaxis of malignant B cells. Conclusion This study extends the spectrum of valuable diagnostic biomarkers in CNSL. In patients with focal brain lesions, measurement of APRIL in CSF could help accelerating the diagnosis of CNSL. Moreover, our results highlight an important role of APRIL and BAFF in the pathophysiology of CNSL.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

APRIL and BAFF: novel biomarkers for central nervous system lymphoma

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In a small sample study of nine patients with PCNSL, the combination of elevated levels of CSF BAFF and its receptor TACI revealed 100% sensitivity and 100% specificity for the diagnosis of PCNSL. 45 …”

Section: Novel Diagnostic Markers For Pcnslmentioning

confidence: 99%

Novel insights into the biomarkers and therapies for primary central nervous system lymphoma

2022

View full text Add to dashboard Cite

Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive extranodal type of non-Hodgkin lymphoma. After the introduction and widespread use of high-dose-methotrexate (HD-MTX)-based polychemotherapy, treatment responses of PCNSL have been improved. However, long-term prognosis for patients who have failed first-line therapy and relapsed remains poor. Less invasive diagnostic markers, including the circulating tumor DNAs (ctDNAs), microRNAs, metabolomic markers, and other novel biomarkers, such as a proliferation inducing ligand (APRIL) and B-cell activating factor of the TNF family (BAFF), have shown potential to distinguish PCNSL at an early stage, and some of them are related with prognosis to a certain extent. Recent insights into novel therapies, including Bruton tyrosine kinase (BTK) inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, PI3K/mTOR inhibitors, and chimeric antigen receptor (CAR) T cells, have revealed encouraging efficacy in treatment response, whereas the duration of response and long-term survival of patients with relapsed or refractory PCNSL (r/r PCNSL) need further improvement. In addition, the diagnostic efficiency of novel markers and the antitumor efficacy of novel therapies are needed to be assessed further in larger clinical trials. This review provides an overview of recent research on novel diagnostic markers and therapeutic strategies for PCNSL.

show abstract

“…In line with these findings, our group has demonstrated a high expression of BAFF as well as its receptors in PCNSL specimens (22), indicating a potential role for autocrine BAFF/BAFF-R signaling in the pathophysiology of PCNSL. Patients with PCNSL showed significantly higher BAFF CSF levels when compared with other focal brain lesions (23,24). However, patients with PCNSL also exhibit higher CSF levels of soluble TACI and soluble BCMA (25), possibly limiting the local availability of BAFF (26).…”

Section: Introductionmentioning

confidence: 98%

The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma

et al. 2020

View full text Add to dashboard Cite

Primary CNS lymphoma (PCNSL) is an aggressive brain tumor. Despite improvements in therapeutic algorithms, long-term survival remains rare, illustrating an urgent need for novel therapeutic targets. BAFF-R is a pro-survival receptor expressed on most malignant B cells, including PCNSL. To date, its role in PCNSL growth remains elusive. Here, we have created a BAFF-R knockout lymphoma cell line (BAFF-R-KO) using CRISPR-Cas9. In serum-starved conditions, BAFF-R-KO cells exhibit decreased viability in vitro compared to BAFF-R + cells. Combining an orthotopic mouse model of PCNSL with chronic cranial windows and intravital microscopy, we have demonstrated a significant delay in tumor growth in mice inoculated with BAFF-R-KO cells compared to BAFF-R + PCNSL. Additionally, median survival of BAFF-R-KO mice was significantly prolonged. Altogether, our results indicate the high potential of BAFF-R as a novel treatment target for PCNSL.

show abstract

CSF TACI and BAFF levels in patients with primary CNS lymphoma as novel diagnostic biomarkers

Cited by 8 publications

References 18 publications

APRIL and BAFF: novel biomarkers for central nervous system lymphoma

APRIL and BAFF: novel biomarkers for central nervous system lymphoma

Novel insights into the biomarkers and therapies for primary central nervous system lymphoma

The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma

Contact Info

Product

Resources

About