Immunological profile of patients with primary progressive multiple sclerosis. Expression of adhesion molecules.

Adhesion molecules are important in the trafficking of peripheral leucocytes into the central nervous system, a major event in the pathogenesis of multiple sclerosis, which is an inflammatory and demyelinating disease. The latest MRI evidence supports clinical divergence between forms of multiple sclerosis with relapses and the primary progressive form without relapses, which shows fewer and smaller inflammatory lesions. With the aim of elucidating whether different pathogenic mechanisms are involved in primary progressive multiple sclerosis, we compared membrane expression of the adhesion molecules ICAM-1 (CD54), LFA-1alpha (CD11a), VLA-4 [alpha(4)/beta(1) integrin (CD49d/CD29)], L-selectin (CD62L) and ICAM-3 (CD50) in peripheral blood and the serum-soluble forms ICAM-1, L-selectin, VCAM-1 and ICAM-3 in 89 patients (39 with the primary progressive form, 25 with the secondary progressive form and 25 with the relapsing-remitting form) and 38 healthy controls. We found a significant decrease in leucocyte surface expression of most of the adhesion molecules tested and an increase in soluble ICAM-1 and L-selectin levels in secondary progressive and relapsing-remitting multiple sclerosis compared with primary progressive multiple sclerosis, which gave results similar to those in controls. These results, which are supported by MRI evidence, show that trafficking of autoreactive leucocytes through the blood-brain barrier is crucial to the pathogenesis of secondary progressive and relapsing-remitting forms of multiple sclerosis, whereas other mechanisms leading to progressive axonal damage would account for primary progressive forms of the disease.

[1]  Cathy J. Price,et al.  Functional anatomy of reading , 2003 .

[2]  C. Price,et al.  Three Distinct Ventral Occipitotemporal Regions for Reading and Object Naming , 1999, NeuroImage.

[3]  F. Barkhof,et al.  Primary and transitional progressive MS , 1999, Neurology.

[4]  G. McDonnell,et al.  Serum soluble adhesion molecules in multiple sclerosis: raised sVCAM-1, sICAM-1 and sE-selectin in primary progressive disease , 1999, Journal of Neurology.

[5]  M. Pender,et al.  Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis , 1998, Annals of neurology.

[6]  C. Price The functional anatomy of word comprehension and production , 1998, Trends in Cognitive Sciences.

[7]  G. McDonnell,et al.  Raised CSF levels of soluble adhesion molecules across the clinical spectrum of multiple sclerosis , 1998, Journal of Neuroimmunology.

[8]  M. Jutila,et al.  Calmodulin Regulates L-Selectin Adhesion Molecule Expression and Function through a Protease-Dependent Mechanism , 1998, Cell.

[9]  R. Rudick,et al.  Axonal transection in the lesions of multiple sclerosis. , 1998, The New England journal of medicine.

[10]  H. Hartung,et al.  Modulation of the expression of integrins on glial cells during experimental autoimmune encephalomyelitis. A central role for TNF-alpha. , 1997, The American journal of pathology.

[11]  Karl J. Friston,et al.  Human Brain Function , 1997 .

[12]  H. Hartung,et al.  The role of adhesion molecules in multiple sclerosis: biology, pathogenesis and therapeutic implications. , 1997, Molecular medicine today.

[13]  A. Thompson,et al.  Longitudinal study of soluble adhesion molecules in multiple sclerosis , 1997, Neurology.

[14]  A J Thompson,et al.  PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS , 1997 .

[15]  J. Dambrosia,et al.  Increases in soluble VCAM‐1 correlate with a decrease in MRI lesions in multiple sclerosis treated with interferon β‐1b , 1997, Annals of neurology.

[16]  R. Hohlfeld,et al.  Biotechnological agents for the immunotherapy of multiple sclerosis. Principles, problems and perspectives. , 1997, Brain : a journal of neurology.

[17]  Karl J. Friston,et al.  Cognitive Conjunction: A New Approach to Brain Activation Experiments , 1997, NeuroImage.

[18]  R. Bergamaschi,et al.  Soluble CD8 and ICAM‐1 in serum and CSF of MS patients treated with 6‐methylprednisolone , 1997, Acta neurologica Scandinavica.

[19]  G. Grau,et al.  Brain microvascular endothelial cells and leukocytes derived from patients with multiple sclerosis exhibit increased adhesion capacity , 1997, Neuroreport.

[20]  R. Salonen,et al.  Therapy with antibody against leukocyte integrin VLA-4 (CD49d) is effective and safe in virus-facilitated experimental allergic encephalomyelitis , 1997, Journal of Neuroimmunology.

[21]  M. Trojano,et al.  Soluble intercellular adhesion molecule-1 in serum and cerebrospinal fluid of clinically active relapsing-remitting multiple sclerosis , 1996, Neurology.

[22]  J. Hodges,et al.  Generating ‘tiger’ as an animal name or a word beginning with T: differences in brain activation , 1996, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[23]  Moses Rodriguez,et al.  Distinct Patterns of Multiple Sclerosis Pathology Indicates Heterogeneity in Pathogenesis , 1996, Brain pathology.

[24]  H. McFarland,et al.  Expression pattern of activation and adhesion molecules on peripheral blood CD4+ T-lymphocytes in relapsing-remitting multiple sclerosis patients: a serial analysis , 1996, Journal of Neuroimmunology.

[25]  A. Lentsch,et al.  The role of cytokines, adhesion molecules, and chemokines in interleukin-2-induced lymphocytic infiltration in C57BL/6 mice. , 1996, The Journal of clinical investigation.

[26]  L. Picker,et al.  Lymphocyte Homing and Homeostasis , 1996, Science.

[27]  S. Reingold,et al.  Defining the clinical course of multiple sclerosis , 1996, Neurology.

[28]  J. Goding,et al.  Monoclonal Antibodies: Principles and Practice , 1996 .

[29]  Richard S. J. Frackowiak,et al.  Noun and verb retrieval by normal subjects. Studies with PET. , 1996, Brain : a journal of neurology.

[30]  X. Montalban,et al.  Different antiganglioside antibody pattern between relapsing‐remitting and progressive multiple sclerosis , 1996, Acta neurologica Scandinavica.

[31]  A. Thompson,et al.  Soluble E-selectin in multiple sclerosis: raised concentrations in patients with primary progressive disease. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[32]  T. Nurmikko,et al.  CSF oligoclonal bands, MRI, and the diagnosis of multiple sclerosis , 1995, Acta Neurologica Scandinavica.

[33]  Y. Ron,et al.  Bothanti-CD11a(LFA-l) and anti-CD11b (MAC-1) therapy delay the onset and diminish the severity of experimental autoimmune encephalomyelitis , 1995, Journal of Neuroimmunology.

[34]  M. Miyasaka,et al.  Antibodies against leukocyte function-associated antigen-1 and against intercellular adhesion molecule-1 together suppress the progression of experimental allergic encephalomyelitis. , 1995, Cellular immunology.

[35]  H. Hartung,et al.  Circulating adhesion molecules and tumor necrosis factor receptor in multiple sclerosis: Correlation with magnetic resonance imaging , 1995, Annals of neurology.

[36]  N. Yanagisawa,et al.  Increased levels of soluble vascular cell adhesion molecule-1 ( VCAM-1) in the cerebrospinal fluid and sera of patients with multiple sclerosis and human T lymphotropic virus type-1-associated myelopathy , 1995, Journal of Neuroimmunology.

[37]  Judith E. Cartwright,et al.  The expression and release of adhesion molecules by human endothelial cell lines and their consequent binding of lymphocytes. , 1995, Experimental cell research.

[38]  J. Alberola-Ila,et al.  Existence of a soluble form of CD50 (intercellular adhesion molecule-3) produced upon human lymphocyte activation. Present in normal human serum and levels are increased in the serum of systemic lupus erythematosus patients. , 1995, Journal of immunology.

[39]  S. Martin,et al.  Circulating forms of ICAM-3 (cICAM-3). Elevated levels in autoimmune diseases and lack of association with cICAM-1. , 1995, Journal of immunology.

[40]  M. Peterson,et al.  Circulating, soluble adhesion proteins in cerebrospinal fluid and serum of patients with multiple sclerosis: Correlation with clinical activity , 1995, Annals of neurology.

[41]  A. Broocks,et al.  Serial analysis of circulating adhesion molecules and TNF receptor in serum from patients a with multinle sclerosis , 1994, Neurology.

[42]  J. Olschowka,et al.  Expression of ICAM-1, VCAM-1, L-selectin, and leukosialin in the mouse central nervous system during the induction and remission stages of experimental allergic encephalomyelitis , 1994, Journal of Neuroimmunology.

[43]  A J Thompson,et al.  A comparison of the pathology of primary and secondary progressive multiple sclerosis. , 1994, Brain : a journal of neurology.

[44]  B. Engelhardt,et al.  Evidence for involvement of ICAM-1 and VCAM-1 in lymphocyte interaction with endothelium in experimental autoimmune encephalomyelitis in the central nervous system in the SJL/J mouse. , 1994, The American journal of pathology.

[45]  T. Springer Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm , 1994, Cell.

[46]  V. Kuchroo,et al.  Cytokines and adhesion molecules contribute to the ability of myelin proteolipid protein-specific T cell clones to mediate experimental allergic encephalomyelitis. , 1993, Journal of immunology.

[47]  A. Gearing,et al.  Circulating adhesion molecules in disease. , 1993, Immunology today.

[48]  G. Hansson,et al.  Adhesion molecule expression on cerebrospinal fluid T lymphocytes: Evidence for common recruitment mechanisms in multiple sclerosis, aseptic meningitis, and normal controls , 1993, Annals of neurology.

[49]  H. Kolb,et al.  Elevated Levels of Circulating Adhesion Molecules in IDDM Patients and in Subjects at Risk for IDDM , 1992, Diabetes.

[50]  F. Sánchez‐Madrid,et al.  Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin , 1992, Nature.

[51]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

[52]  H. Lassmann Basic mechanisms of brain inflammation. , 1997, Journal of neural transmission. Supplementum.

[53]  J. Goding 8 – Production of Monoclonal Antibodies , 1996 .

[54]  R. Todd Constable,et al.  Localization of semantic processing using functional magnetic resonance imaging , 1994 .

[55]  S. Petersen,et al.  Practice-related changes in human brain functional anatomy during nonmotor learning. , 1994, Cerebral cortex.