Changes in serum levels of ICAM and TNF-R correlate with disease activity in multiple sclerosis

Objective: To study the change in serum levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble tumor necrosis factor receptors (sTNF-Rs) in MS patients in relation to clinical disease activity and changes on brain MRI. Background: Circulating forms of adhesion molecules or soluble receptors may be released from cells as a consequence of activation and may be useful markers for inflammation. Methods: During a prospective longitudinal study over 1 year, 40 patients with MS underwent frequent imaging of the brain (22 MR images per patient) at the time of blood sampling as well as monthly neurologic examinations, and scoring on Kurtzke’s Expanded Disability Status Scale (EDSS) and ambulation index (AI). Results: Patients with relapsing–progressive disease had the highest levels of sICAM-1 whereas patients with progressive disease had the highest levels of sTNF-Rs. Fluctuations in sICAM-1 correlated with the occurrence of attacks in patients with relapsing and relapsing–progressive disease. In patients with relapsing–progressive MS, an increase in sICAM-1 level preceded the appearance of new gadolinium (Gd) enhancing lesions on MRI. In patients with progressive disease, an increase in sTNF-R p55 level preceded the appearance of new Gd enhancing lesions on MRI, whereas a decrease in sICAM-1 levels correlated with the appearance of new Gd enhancing lesions. Conclusions: These results demonstrate a linkage between sICAM-1 and sTNF-R levels and disease activity in MS. Furthermore, patients with progressive disease appear to have a different immunologic stage of disease in which immune changes are tightly linked with changes on MRI. The demonstration of a correlation in individual patients between immunologic events and changes in disease activity has implications for monitoring patients undergoing treatment and for monitoring disease progression.

[1]  R. Kikinis,et al.  Quantitative follow‐up of patients with multiple sclerosis using MRI: Technical aspects , 1999, Journal of magnetic resonance imaging : JMRI.

[2]  R. Killiany,et al.  Quantitative follow‐up of patients with multiple sclerosis using MRI: Reproducibility , 1999, Journal of magnetic resonance imaging : JMRI.

[3]  H. Weiner,et al.  Elevated interleukin-12 in progressive multiple sclerosis correlates with disease activity and is normalized by pulse cyclophosphamide therapy. , 1998, The Journal of clinical investigation.

[4]  H. Weiner,et al.  Multiple sclerosis: what have we learned from magnetic resonance imaging studies? , 1998, Archives of internal medicine.

[5]  M. Trojano,et al.  Soluble Intercellular Adhesion Molecule-1 (sICAM-1) in serum and cerebrospinal fluid of demyelinating diseases of the central and peripheral nervous system , 1998, Multiple sclerosis.

[6]  A. Consiglio,et al.  Tumor necrosis factor α and its receptors in relapsing-remitting multiple sclerosis , 1997, Journal of the Neurological Sciences.

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

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

[9]  J. Baudewig,et al.  Soluble adhesion molecules (sVCAM‐1 and sICAM‐1) in cerebrospinal fluid and serum correlate with MRI activity in multiple sclerosis , 1997, Annals of neurology.

[10]  H. Weiner,et al.  Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[11]  A. Consiglio,et al.  Tumor necrosis factor alpha and its receptors in relapsing-remitting multiple sclerosis. , 1997, Journal of the neurological sciences.

[12]  F. Barkhof,et al.  Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2 , 1996, Neurology.

[13]  T. Yousry,et al.  Multiple sclerosis: prospective analysis of TNF-α and 55 kDa TNF receptor in CSF and serum in correlation with clinical and MRI activity , 1996, Journal of Neuroimmunology.

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

[15]  S. Hawkins,et al.  Serum and cerebrospinal fluid levels of soluble adhesion molecules in multiple sclerosis: predominant intrathecal release of vascular cell adhesion molecule-1 , 1996, Journal of Neuroimmunology.

[16]  W. Eric L. Grimson,et al.  Adaptive Segmentation of MRI Data , 1995, CVRMed.

[17]  B. Weinstock-Guttman,et al.  A phase III trial of intramuscular recombinant interferon beta as treatment for exacerbating-remitting multiple sclerosis: design and conduct of study and baseline characteristics of patients , 1995 .

[18]  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.

[19]  C. Raine,et al.  The adhesion molecule and cytokine profile of multiple sclerosis lesions , 1995, Annals of neurology.

[20]  A. Broocks,et al.  Tumor necrosis factor‐α messenger RNA expression in patients with relapsing‐remitting multiple sclerosis is associated with disease activity , 1995, Annals of neurology.

[21]  J. Simon,et al.  A phase III trial of intramuscular recombinant interferon beta as treatment for exacerbating-remitting multiple sclerosis: design and conduct of study and baseline characteristics of patients. Multiple Sclerosis Collaborative Research Group (MSCRG). , 1995, Multiple sclerosis.

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

[23]  R. Heller,et al.  Tumor necrosis factor receptor-mediated signaling pathways , 1994, The Journal of cell biology.

[24]  W. Buurman,et al.  Slow release of soluble TNF receptors by monocytes in vitro. , 1994, Journal of immunology.

[25]  Terry Farrah,et al.  The TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and death , 1994, Cell.

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

[27]  N. Yanagisawa,et al.  Increases levels of circulating intercellular adhesion molecule‐1 in multiple sclerosis and human T‐lymphotropic virus type I‐associated myelopathy , 1993, Annals of neurology.

[28]  D. Paty,et al.  Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis , 1993, Neurology.

[29]  E. Thompson,et al.  Increased levels of circulating ICAM-1 in serum and cerebrospinal fluid of patients with active multiple sclerosis. Correlation with TNF-α and blood-brain barrier damage , 1993, Journal of Neuroimmunology.

[30]  G. Grau,et al.  Tumor necrosis factor alpha production as a possible predictor of relapse in patients with multiple sclerosis. , 1992, European cytokine network.

[31]  Ron Kikinis,et al.  4D Connected component labelling applied to quantitative analysis of MS lesion temporal development , 1992, 1992 14th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[32]  D. Wallach,et al.  Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors , 1992, The Journal of experimental medicine.

[33]  M. Sharief,et al.  Association between Tumor Necrosis Factor-α and Disease Progression in Patients with Multiple Sclerosis , 1991 .

[34]  C. Brosnan,et al.  Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. , 1991, The Journal of clinical investigation.

[35]  M. Esiri,et al.  Blood-brain barrier damage in acute multiple sclerosis plaques. An immunocytological study. , 1991, Brain : a journal of neurology.

[36]  R. Sobel,et al.  Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. , 1990, The American journal of pathology.

[37]  R. Poston,et al.  Pathology, histochemistry and immunocytochemistry of lesions in acute multiple sclerosis , 1989, Journal of the Neurological Sciences.

[38]  T. Waldmann,et al.  Elevated levels of soluble interleukin-2 receptors in multiple sclerosis. , 1988, The New England journal of medicine.

[39]  H. Kirchner,et al.  Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: Do cytokines trigger off exacerbations? , 1988, Acta neurologica Scandinavica.

[40]  D. Clifford,et al.  Elevated serum interleukin-2 levels in chronic progressive multiple sclerosis. , 1988, The New England journal of medicine.

[41]  S. Zeger,et al.  Longitudinal data analysis using generalized linear models , 1986 .

[42]  Prineas Jw,et al.  Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. , 1978 .

[43]  J. Prineas,et al.  Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. , 1978, Laboratory investigation; a journal of technical methods and pathology.