Pathogenesis – Immunology Poster Presentation

P0957 - Does peripheral immune profile reflect intrathecal inflammation in multiple sclerosis patients at time of diagnosis? (ID 1728)

Speakers
  • R. Magliozzi
Authors
  • R. Magliozzi
  • A. Vella
  • D. Postinghel
  • V. Mazziotti
  • S. Rossi
  • A. Giacomazzi
  • M. Castellaro
  • D. Marastoni
  • F. Crescenzo
  • V. Bronte
  • S. Monaco
  • M. Calabrese
Presentation Number
P0957
Presentation Topic
Pathogenesis – Immunology

Abstract

Background

Intrathecal inflammation, possibly compartmentalized in meninges, perivascular cuffs and cerebrospinal fluid (CSF), represents one of the main features of Multiple Sclerosis (MS). Recent studies have shown that a specific panel of CSF molecules present at diagnosis may be able to stratify naïve MS patients in two subgroups according to the high (SMhigh) or low (MSlow) level of CSF inflammation and cortical damage and to predict their disease outcome.

Objectives

Verify whether the inflammatory CSF intrathecal profile may correlate with the protein and cell inflammatory profile of the paired blood at diagnosis.

Methods

Immunoassay protein analysis of 79 inflammatory molecules was evaluated in paired CSF and serum obtained at diagnosis by 71 patients with MS and 36 subjects with other neurodegenerative diseases. Each patient was annually subjected to detailed clinical/radiological examination by 3 T-MRI. By using flow-cytometry we also analysed the specific blood immunophenotypes in paired CSF and blood samples of a subgroup of 15 MS patients.

Results

We found significant (p<0,01) correlations between number of spinal lesions both at diagnosis (T0) and after 2 years and the expressions of CXCL16, (r=0.54), CXCL5, (r=0.46), sTNFR1, (r= 0.39), TWEAK (r=0.43) and finally IL12p70 (r=0.39), as well as with number of blood total CD19+ B cells (r= -0.93; p<0.05) in MS patients but not in controls. However, no correlation between the protein inflammatory profile of paired CSF/serum samples has been revealed, with the only exception of interleukin 10 (IL-10), which was found elevated in both CSF (p<0.01) and serum (p<0.05) of MShigh compared to MSlow patients. Significant correlation was measured between IL-10 serum levels and the number of B cells in the blood (r=0.67; p<0.01), in particular with a subset of switched memory CD19+CD27+IgD- B cells and in particular in the MShigh group. In addition, positive correlation (p<0.05) was found between blood exhausted CD19+CD27-IgD- B cells and number white matter lesions at diagnosis (r=0,55), volume of white matter lesions (r=0.69), global cortical thickness (r=0.71), number of cortical lesions (r=0.79), volume of cortical lesions (r=0.80) and global cortical thickness (r=0.82). On the contrary, the percentage of some memory CD19+CD27-IgG+B cells correlates (p<0.05) with the cortical thickness (r=0.70) and age at diagnosis (r= -0.67). When we analysed possible correlation between blood and CSF immunophenotypes at diagnosis, we found significant correlation (r=0.74; p<0.05) between blood naïve B cells (CD19+CD27-IgD+) and CSF memory CD19+CD27-IgG+B cells.

Conclusions

Serum inflammatory profile at diagnosis only partially reflects intrathecal CSF inflammation. Only IL-10 appeared to represent a useful link between CSF and serum inflammation at diagnosis and may help to identify a subgroup pf MS patients with high involvement of B lymphocytes in early MS pathogenesis.

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