SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of multiple sclerosis patients

Abstract

We aimed to evaluate SIGLEC1 (CD169) as a biomarker in multiple sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the presence of SIGLEC1+ myeloid cells in demyelinating diseases. We performed flow cytometry-based measurements of SIGLEC1 expression on monocytes in 86 MS patients, 41 NMOSD patients and 31 healthy controls. Additionally, we histologically evaluated the presence of SIGLEC1+ myeloid cells in acute and chronic MS brain lesions as well as other neurological diseases. We found elevated SIGLEC1 expression in 16/86 (18.6%) MS patients and 4/41 (9.8%) NMOSD patients. Almost all MS patients with high SIGLEC1 levels received exogenous interferon beta as an immunomodulatory treatment and only a small fraction of MS patients without interferon treatment had increased SIGLEC1 expression. In our cohort, SIGLEC1 expression on monocytes was—apart from those patients receiving interferon treatment—not significantly increased in patients with MS and NMOSD, nor were levels associated with more severe disease. SIGLEC1+ myeloid cells were abundantly present in active MS lesions as well as in a range of acute infectious and malignant diseases of the central nervous system, but not chronic MS lesions. The presence of SIGLEC1+ myeloid cells in brain lesions could be used to investigate the activity in an inflammatory CNS lesion.

Differential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer’s disease

“…Interestingly, CD169 (or Siglec1) was proposed as an indicator of the activity in an inflammatory CNS, due to the results showing that CD169-expressing myeloid cells were abundantly located in an active inflammatory site of the CNS, including in active multiple sclerosis lesions, acute infectious and malignant diseases. Such cells were suggested to support the activation of adaptive immune responses 38 . Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in CSF is hypothesized to increase in response to microglial activation due to neurodegenerative processes and is elevated in AD 39 , 40 .…”

Screening key genes and signaling pathways in COVID-19 infection and its associated complications by integrated bioinformatics analysis

“…CXCL10 [69], ISG15 [70], SIGLEC1 [71], CXCL9 [72], IFIT3 [73], KLF15 [74] and SPRR3 [75] have a potential role in the diagnosis and treatment of cardiovascular diseases. CXCL10 [76], SIGLEC1 [77] and IL1R2 [78] have been suggested to be associated with neurological diseases. CXCL9 [79], SIGLEC1 [80], IL1R2 [81], KLF15 [82] and CD207 [83] [146], STAT4 [147], CXCL8 [148], KLF2 [149], ADM (adrenomedullin) [150], EGR1 [151], TRIB1 [152], SOD2 [153], OXSR1 [154], IL6R [155], CD44 [156], LRG1 [157], PFKFB2 [158], PACSIN2 [159], MYH9 [160], DOT1L [161], CXCL16 [162], PTEN (phosphatase and tensin homolog) [163], FOXO3 [164], DDIT4 [165], PINK1 [166], IQGAP1 [167], ADIPOR1 [168], MTMR3 [169], USF2 [170], SGK1 [171], GSTO2 [172], ETS2 [173], TKT (transketolase) [174], CMIP (c-Maf inducing protein) [175], THBD (granzyme A)…”

“…Due to the advancement of NGS technology, the genetic modifications due to disease development can be detected, indicating gene targets for diagnosis, therapy and prognosis of infectious diseases. In the present investigation, a total of 738 DEGs between COVID-19 samples and non COVID-19 samples were identified, consisting of 415 [76], SIGLEC1 [77] and IL1R2 [78] have been suggested to be associated with neurological diseases. CXCL9 [79], SIGLEC1 [80], IL1R2 [81], KLF15 [82] and CD207 [83] [146], STAT4 [147], CXCL8 [148], KLF2 [149], ADM (adrenomedullin) [150], EGR1 [151], TRIB1 [152], SOD2 [153] [162], PTEN (phosphatase and tensin homolog) [163], FOXO3 [164], DDIT4 [165], PINK1 [166], IQGAP1 [167], ADIPOR1 [168], MTMR3 [169] [464], IFNG (interferon gamma) [465], IFIH1 [466], STAT1 [467], CCR5 [468], ADCY5 [469], MT2A [470], DPP4 [471], FASLG (Fas ligand) [472], HLA-DMB [473], CD3D [474], CMKLR1 [475], ICOS (inducible T cell costimulator) [476] [492], CFB (complement factor B) [493], TLR7 [494], SLAMF1 [495], BPIFA1 [496], CD300E…”

Differential transcriptomic changes in the central nervous system and urinary bladders of mice infected with a coronavirus

“…Siglec1 gene encodes a member of the immunoglobulin superfamily expressed mostly in monocytes and some macrophages. Elevated SIGLEC1 protein expression was found in the brain but not in the blood of MS patients [130]. However, expression of SIGLEC1 by CD14 + monocytes was significantly increased in MS patients with the progressive form of the disease [79].…”