A highly sensitive sandwich ELISA to detect CSF progranulin: A potential biomarker for CNS disorders

Yanqing Li, Dongyang Wang, Ya Li, Jiuling Zhu, Junli Zhao, Yanchun Deng, Emily J. Rogalski, Eileen H. Bigio, Alfred W. Rademaker, Haibin Xia*, Qinwen Mao

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Progranulin (PGRN) plays critical roles in inflammation, tumorigenesis, and neurodegeneration. PGRN levels in blood and cerebrospinal fluid (CSF) are being increasingly investigated as potential biomarkers for these disorders. However, the value of CSF PGRN as a biomarker has been limited because currently available commercial enzyme-linked immunosorbent assay (ELISA) kits have suboptimal sensitivity for detecting CSF PGRN. In this study, pairs of monoclonal antibodies (MAbs) were first screened from eleven monoclonal antiPGRN antibodies using indirect ELISA, then a sandwich ELISA was established using the 2 optimized MAbs. This system displayed high sensitivity, with a lower limit of detection of 60.0 pg/mL and a lower limit of quantification of 150 pg/mL. By using this ELISA system, we showed varied CSF PGRN levels in different brain disorders. For example, as compared with the normal controls, patients with Alzheimer disease or multiple sclerosis showed mildly increased CSF PGRN; those with aseptic encephalitis or neuropsychiatric systemic lupus erythematosus showed moderately increased CSF PGRN; those with bacterial leptomeningitis showed severely increased CSF PGRN. Additionally, determining CSF PGRN levels could monitor CNS metastasis and CSF seeding of carcinomas. These results indicate that this system can be valuable in studying the diagnostic and prognostic value of CSF PGRN in brain disorders.

Original languageEnglish (US)
Pages (from-to)406-415
Number of pages10
JournalJournal of neuropathology and experimental neurology
Volume78
Issue number5
DOIs
StatePublished - Jan 1 2019

Keywords

  • Biomarker
  • Brain disorders
  • Cerebrospinal fluid
  • Double antibody sandwich ELISA (DAS-ELISA)
  • Monoclonal antibody
  • Progranulin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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