Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation

Laura Piccio, Cecilia Buonsanti, Marina Cella, Ilaria Tassi, Robert E. Schmidt, Chiara Fenoglio, John Rinker, Robert T. Naismith, Paola Panina-Bordignon, Nadia Passini, Daniela Galimberti, Elio Scarpini, Marco Colonna, Anne H. Cross

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM-2) is a membrane-bound receptor expressed by microglia and macrophages. Engagement of TREM-2 on these cells has been reported to reduce inflammatory responses and, in microglial cells, to promote phagocytosis. TREM-2 function is critical within the CNS, as its genetic deficiency in humans causes neurodegeneration with myelin and axonal loss. Blockade of TREM-2 worsened the mouse model for multiple sclerosis. In the present study, a soluble form of TREM-2 protein has been identified by immunoprecipitation and by ELISA. Soluble TREM-2 protein (sTREM-2) was detected in human CSF, and was compared among subjects with relapsing-remitting multiple sclerosis (RR-MS; n =D; 52), primary progressive multiple sclerosis (PP-MS; n =D; 21), other inflammatory neurologic diseases (OIND; n =D; 19), and non-inflammatory neurologic diseases (NIND; n =D; 41). Compared to NIND subjects, CSF sTREM-2 levels were significantly higher in RR-MS (P =D; 0.004 by ANOVA) and PP-MS (P < 0.001) subjects, as well as in OIND (P < 0.001) subjects. In contrast, levels of sTREM-2 in blood did not differ among the groups. Furthermore, TREM-2 was detected on a subset of CSF monocytes by flow cytometry, and was also highly expressed on myelin-laden macrophages in eight active demyelinating lesions from four autopsied multiple sclerosis subjects. The elevated levels of sTREM-2 in CSF of multiple sclerosis patients may inhibit the anti-inflammatory function of the membrane-bound receptor suggesting sTREM-2 to be a possible target for future therapies.

Original languageEnglish
Pages (from-to)3081-3091
Number of pages11
JournalBrain
Volume131
Issue number11
DOIs
StatePublished - Nov 1 2008

Keywords

  • Immune regulation
  • Macrophages
  • Microglia
  • Multiple sclerosis
  • Neuroinflammation

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