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

Brain. 2008 Nov;131(Pt 11):3081-91. doi: 10.1093/brain/awn217. Epub 2008 Sep 12.

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 = 52), primary progressive multiple sclerosis (PP-MS; n = 21), other inflammatory neurologic diseases (OIND; n = 19), and non-inflammatory neurologic diseases (NIND; n = 41). Compared to NIND subjects, CSF sTREM-2 levels were significantly higher in RR-MS (P = 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cells, Cultured
  • Dendritic Cells / metabolism
  • Encephalomyelitis / blood
  • Encephalomyelitis / cerebrospinal fluid*
  • Encephalomyelitis / pathology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Foam Cells / metabolism
  • Foam Cells / pathology
  • Humans
  • Male
  • Membrane Glycoproteins / blood
  • Membrane Glycoproteins / cerebrospinal fluid*
  • Middle Aged
  • Monocytes / metabolism
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis, Chronic Progressive / blood
  • Multiple Sclerosis, Chronic Progressive / cerebrospinal fluid
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Pons / metabolism
  • Pons / pathology
  • Receptors, Immunologic / blood
  • Young Adult

Substances

  • Membrane Glycoproteins
  • Receptors, Immunologic
  • TREM2 protein, human