title: Comprehensive immunophenotyping of cerebrospinal fluid cells in patients with neuroimmunological diseases.
abstract: We performed unbiased, comprehensive immunophenotyping of cerebrospinal fluid (CSF) and blood leukocytes in 221 subjects referred for the diagnostic work-up of neuroimmunological disorders to obtain insight about disease-specific phenotypes of intrathecal immune responses. Quantification of 14 different immune cell subsets, coupled with the assessment of their activation status, revealed physiological differences between intrathecal and systemic immunity, irrespective of final diagnosis. Our data are consistent with a model where the CNS shapes intrathecal immune responses to provide effective protection against persistent viral infections, especially by memory T cells, plasmacytoid dendritic cells, and CD56(bright) NK cells. Our data also argue that CSF immune cells do not simply reflect cells recruited from the periphery. Instead, they represent a mixture of cells that are recruited from the blood, have been activated intrathecally and leave the CNS after performing effector functions. Diagnosis-specific differences provide mechanistic insight into the disease process in the defined subtypes of multiple sclerosis (MS), neonatal onset multisystem inflammatory disease, and Aicardi-Goutières syndrome. This analysis also determined that secondary-progressive MS patients are immunologically closer to relapsing-remitting patients as compared with patients with primary-progressive MS. Because CSF immunophenotyping captures the biology of the intrathecal inflammatory processes, it has the potential to guide optimal selection of immunomodulatory therapies in individual patients and monitor their efficacy. Our study adds to the increasing number of publications that demonstrate poor correlation between systemic and intrathecal inflammatory biomarkers in patients with neuroimmunological diseases and stresses the importance of studying immune responses directly in the intrathecal compartment.
authors: Neuroimmunological Diseases Unit, Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892;
authors: Sungpil
authors: S
authors: Han
authors: Yen Chih
authors: YC
authors: Lin
authors: Tianxia
authors: T
authors: Wu
authors: Alan D
authors: AD
authors: Salgado
authors: Ina
authors: I
authors: Mexhitaj
authors: Simone C
authors: SC
authors: Wuest
authors: Elena
authors: E
authors: Romm
authors: Joan
authors: J
authors: Ohayon
authors: Raphaela
authors: R
authors: Goldbach-Mansky
authors: Adeline
authors: A
authors: Vanderver
authors: Adriana
authors: A
authors: Marques
authors: Camilo
authors: C
authors: Toro
authors: Peter
authors: P
authors: Williamson
authors: Irene
authors: I
authors: Cortese
authors: Bibiana
authors: B
authors: Bielekova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D020274:Autoimmune Diseases of the Nervous System / Q000097:blood / Q000134:cerebrospinal fluid* / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping / Q000379:methods*; D007249:Inflammation / Q000097:blood / Q000134:cerebrospinal fluid* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000134:cerebrospinal fluid* / Q000276:immunology; D009421:Nervous System Malformations / Q000097:blood / Q000134:cerebrospinal fluid* / Q000276:immunology; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D019002:CD56 Antigen