RT Journal Article SR Electronic T1 Altered CSF Albumin Quotient Links Peripheral Inflammation and Brain Damage in MS JF Neurology - Neuroimmunology Neuroinflammation JO Neurol Neuroimmunol Neuroinflamm FD Lippincott Williams & Wilkins SP e951 DO 10.1212/NXI.0000000000000951 VO 8 IS 2 A1 Puthenparampil, Marco A1 Tomas-Ojer, Paula A1 Hornemann, Thorsten A1 Lutterotti, Andreas A1 Jelcic, Ilijas A1 Ziegler, Mario A1 Hülsmeier, Andreas J. A1 Cruciani, Carolina A1 Faigle, Wolfgang A1 Martin, Roland A1 Sospedra, Mireia YR 2021 UL http://nn.neurology.org/content/8/2/e951.abstract 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