A Highly Sensitive Sandwich ELISA to Detect CSF Progranulin: A Potential Biomarker for CNS Disorders
| Autor: | Haibin Xia, Alfred Rademaker, Qinwen Mao, Dongyang Wang, Ya Li, Yanchun Deng, Junli Zhao, Yanqing Li, Eileen H. Bigio, Jiuling Zhu, Emily Rogalski |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
medicine.drug_class Enzyme-Linked Immunosorbent Assay Inflammation Monoclonal antibody Pathology and Forensic Medicine Cohort Studies Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience Progranulins 0302 clinical medicine Cerebrospinal fluid Central Nervous System Diseases medicine Humans Aged biology business.industry Multiple sclerosis Reproducibility of Results General Medicine Middle Aged medicine.disease HEK293 Cells Neurology Monoclonal Immunology biology.protein Biomarker (medicine) Neurology (clinical) medicine.symptom Alzheimer's disease Antibody business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuropathology & Experimental Neurology. 78:406-415 |
| ISSN: | 1554-6578 0022-3069 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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