CSF TACI and BAFF levels in patients with primary CNS lymphoma as novel diagnostic biomarkers.
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ABSTRACT:
SUBMITTER: Mizutani H
PROVIDER: S-EPMC6292192 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Publications
CSF TACI and BAFF levels in patients with primary CNS lymphoma as novel diagnostic biomarkers.
Mizutani Hironori H Nakane Shunya S Ikeda Tokunori T Nakamura Hideo H Takamatsu Koutaro K Makino Keishi K Tawara Nozomu N Mukaino Akihiro A Watari Mari M Matsui Hirotaka H Mukasa Akitake A Ando Yukio Y
Annals of clinical and translational neurology 20181019 12
We used an enzyme-linked immunosorbent assay to measure pretreatment B cell-activating factor belonging to the tumour necrosis factor family (BAFF) and transmembrane activator and CAML-interactor (TACI) levels in CSF and serum collected from patients with primary central nervous system lymphoma (PCNSL) and control groups. The decision tree analysis of CSF TACI and BAFF levels for patients with a PCNSL diagnosis showed 100% sensitivity and 100% specificity when we attempted to differentiate PCNSL ...[more]
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Project description:BackgroundPrimary central nervous system lymphoma (PCNSL) is rare and there is limited genomic and immunological information available. Incidental clinical and radiographic responses have been reported in PCNSL patients treated with immune checkpoint inhibitors.Materials and methodsTo genetically characterize and ascertain if the majority of PCNSL patients may potentially benefit from immune checkpoint inhibitors, we profiled 48 subjects with PCNSL from 2013 to 2018 with (1) next-generation sequencing to detect mutations, gene amplifications, and microsatellite instability (MSI); (2) RNA sequencing to detect gene fusions; and (3) immunohistochemistry to ascertain PD-1 and PD-L1 expression. Tumor mutational burden (TMB) was calculated using somatic nonsynonymous missense mutations.ResultsHigh PD-L1 expression (>5% staining) was seen in 18 patients (37.5%), and intermediate expression (1-5% staining) was noted in 14 patients (29.2%). Sixteen patients (33.3%) lacked PD-L1 expression. PD-1 expression (>1 cell/high-power field) was seen in 12/14 tumors (85.7%), uncorrelated with PD-L1 expression. TMB of greater than or equal to 5 mutations per megabase (mt/Mb) occurred in 41/42 tumors, with 19% (n = 8) exhibiting high TMB (≥17 mt/Mb), 71.4% (n = 30) exhibiting intermediate TMB (7-16 mt/Mb), and 9.5% (n = 4) exhibiting low TMB (≤6 mt/Mb). No samples had MSI. Twenty-six genes showed mutations, most frequently in MYD88 (34/42, 81%), CD79B (23/42, 55%), and PIM1 (23/42, 55%). Among 7 cases tested with RNA sequencing, an ETV6-IGH fusion was found. Overall, 18/48 samples expressed high PD-L1 and 38/42 samples expressed intermediate to high TMB.ConclusionsBased on TMB biomarker expression, over 90% of PCNSL patients may benefit from the use of immune checkpoint inhibitors.
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