Title |
Cerebrospinal Fluid Cytokines Correlate With Aseptic Meningitis and Blood–Brain Barrier Function in Neonatal‐Onset Multisystem Inflammatory Disease: Central Nervous System Biomarkers in Neonatal‐Onset Multisystem Inflammatory Disease Correlate With Central Nervous System Inflammation
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Published in |
Arthritis & Rheumatology, May 2017
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DOI | 10.1002/art.40055 |
Pubmed ID | |
Authors |
Jackeline Rodriguez‐Smith, Yen‐Chih Lin, Wanxia Li Tsai, Hanna Kim, Gina Montealegre‐Sanchez, Dawn Chapelle, Yan Huang, Cailin H. Sibley, Massimo Gadina, Robert Wesley, Bibiana Bielekova, Raphaela Goldbach‐Mansky |
Abstract |
To evaluate proinflammatory cytokines and leukocyte subpopulations in cerebrospinal spinal fluid (CSF) and blood of NOMID patients post-treatment; and to compare inflammatory cytokines in CSF and blood in 6 patients treated with two IL-1 blockers, anakinra and canakinumab. We immunophenotyped CSF on 17 anakinra-treated pediatric NOMID patients during routine follow-up visits between December 2011 and October 2013 and analyzed CSF cytokine levels in baseline and 3-5 years follow-up samples compared to healthy controls. Elevated CSF IL-6, IP-10/CXCL10, IL-18 levels, and monocyte and granulocytes counts significantly decreased with anakinra treatment, but did not normalize to control levels, even in patients fulfilling criteria of "clinical remission" (CR). CSF IL-6 and IL-18 levels significantly correlate with measures of blood brain barrier (BBB) function, specifically CSF protein (r=0.75; r=0.81 respectively); and albumin quotient (r=0.79, r=0.68 respectively). Median CSF WBC levels (10.2 vs. 3.7cell/mm3) and CSF IL-6 levels (150.7 vs. 28.5pg/ml) were significantly higher when patients received canakinumab than anakinra despite similar serum cytokine levels. CSF leukocyte subpopulations and cytokine levels significantly improve with optimized IL-1 blocking treatment but do not normalize. The correlation of CSF IL-6, IP-10/CXCL10 and IL-18 with clinical-laboratory measures of inflammation and BBB function suggests a role as biomarkers in CNS inflammation. The difference in inhibition of CSF biomarkers between two IL-1 blocking agents, anakinra and canakinumab, suggests differences in efficacy in the intrathecal compartment, with anakinra being more effective. Our data indicate that intrathecal immune responses shape CNS inflammation and should be assessed in addition to blood markers. This article is protected by copyright. All rights reserved. |
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