PT  - JOURNAL ARTICLE
AU  - Puthenparampil, Marco
AU  - Tomas-Ojer, Paula
AU  - Hornemann, Thorsten
AU  - Lutterotti, Andreas
AU  - Jelcic, Ilijas
AU  - Ziegler, Mario
AU  - Hülsmeier, Andreas J.
AU  - Cruciani, Carolina
AU  - Faigle, Wolfgang
AU  - Martin, Roland
AU  - Sospedra, Mireia
TI  - Altered CSF Albumin Quotient Links Peripheral Inflammation and Brain Damage in MS
AID  - 10.1212/NXI.0000000000000951
DP  - 2021 Mar 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e951
VI  - 8
IP  - 2
4099  - http://nn.neurology.org/content/8/2/e951.short
4100  - http://nn.neurology.org/content/8/2/e951.full
SO  - Neurol Neuroimmunol Neuroinflamm2021 Mar 01; 8
AB  - Objective CNS damage can increase the susceptibility of the blood-brain barrier (BBB) to changes induced by systemic inflammation. The aim of this study is to better understand BBB permeability in patients with MS and to examine whether compromised BBB integrity in some of these patients is associated with CNS damage and systemic inflammation.Methods Routine CSF measurements of 121 patients with MS were analyzed including number and type of infiltrating cells, total protein, lactate, and oligoclonal bands, as well as intrathecal production of immunoglobulins and CSF/serum quotients for albumin, immunoglobulins, and glucose. In addition, in a subcohort of these patients, we performed ex vivo immunophenotyping of CSF-infiltrating and paired circulating lymphocytes using a panel of 13 monoclonal antibodies, we quantified intrathecal neurofilament light chain (NF-L) and chitinase 3-like 1 (CHI3L1), and we performed intrathecal lipidomic analysis.Results Patients with MS with abnormal high levels of albumin in the CSF showed a distinct CSF cell infiltrate and markers of CNS damage such as increased intrathecal levels of NF-L and CHI3L1 as well as a distinct CSF lipidomic profile. In addition, these patients showed higher numbers of circulating proinflammatory Th1 and Th1* cells compatible with systemic inflammation. Of interest, the abnormally high levels of albumin in the CSF of those patients were preserved over time.Conclusions Our results support the hypothesis that CNS damage may increase BBB vulnerability to systemic inflammation in a subset of patients and thus contribute to disease heterogeneity.BBB=blood-brain barrier; CHI3L1=chitinase 3-like 1; FADS3=fatty acid desaturase 3; HLA=human leukocyte antigen; IFN=interferon; Ig=immunoglobulin; NF-L=neurofilament light chain; OIND=other inflammatory neurologic diseases; ONIND=other noninflammatory neurologic diseases; PC=phosphatidylcholine; QAlb=serum albumin quotient; QNorm=normal QAlb; RBC=red blood cell; SAdienine=sphingadienine; SM=sphingomyelin