Antimyelin basic protein and antimyelin antibody‐producing cells in multiple sclerosis

Olsson, Tomas; Baig, Shahid; Höjeberg, Bo; Link, Hans

doi:10.1002/ana.410270207

Cited by 123 publications

(55 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In MS, we recently showed elevated numbers of plasma cells producing autoantibodies against myelin antigens in CSF, but not in blood (24). Such a sequestration of the immune response to target may also occur for MBP-reactive T cells in MS since such cells were 70-fold more common among CSF cells than PBL.…”

Section: Discussionmentioning

confidence: 97%

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Olsson¹,

Zhi²,

Höjeberg³

et al. 1990

J. Clin. Invest.

346

160

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a disease with unknown cause characterized by inflammation and demyelination in the central nervous system. Although an autoimmune pathogenesis has been suggested, there are no conclusive data on the number of T cells autoreactive with myelin antigens in MS compared to controls. We showed that T lymphocytes secreting interferony in response to possible target autoantigens are severalfold more common among PBL mononuclear cells in patients with MS than in patients with aseptic meningitis and tension headache. On average T cells reactive with myelin basic protein (MBP), two different MBP peptides, or with proteolipid protein amounted to 2.7-5.2/105 PBL from MS patients. MBPreactive T cells were still more frequent among mononuclear cells isolated from the cerebrospinal fluid (CSF; 185/10O CSF cells). We concluded that T cells reactive with myelin autoantigens are strongly increased in MS. This approach to detect them could allow definition of immunodominant T cell epitopes in individual MS patients, and thereby enable further development towards specific immunotherapy. (J. Clin. Invest. 1990. 86:981-985.)

show abstract

Section: Discussionmentioning

confidence: 97%

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Olsson¹,

Zhi²,

Höjeberg³

et al. 1990

J. Clin. Invest.

346

160

View full text Add to dashboard Cite

show abstract

“…CSF antibodies have been reported to react with MOG, 26 MBP, 27 and PLP. 28 In addition, CSF B cells reactive with MBP, 29 MAG, 30 and MOG 31 have been found in patients with MS. However, it has also been reported that CSF antibodies do not react with MOG, MBP, or PLP.…”

Section: Effect Of Methylprednisolone On the Cns Antibody Re-mentioning

confidence: 99%

Antigen microarrays identify CNS-produced autoantibodies in RRMS

Quintana¹,

Farez²,

Izquierdo³

et al. 2012

Neurology

View full text Add to dashboard Cite

Objective: Multiple sclerosis (MS) is characterized by the local production of antibodies in the CNS and the presence of oligoclonal bands in the CSF. Antigen arrays allow the study of antibody reactivity against a large number of antigens using small volumes of fluid with greater sensitivity than ELISA. We investigated whether there were unique autoantibodies in the CSF of patients with MS as measured by antigen arrays and whether these antibodies differed from those in serum. Methods:We used antigen arrays to analyze the reactivity of antibodies in matched serum and CSF samples of 20 patients with untreated relapsing-remitting MS (RRMS), 26 methylprednisolone-treated patients with RRMS, and 20 control patients with other noninflammatory neurologic conditions (ONDs) against 334 different antigens including heat shock proteins, lipids, and myelin antigens. Results:We found different antibody signatures in matched CSF and serum samples The targets of these antibodies included epitopes of the myelin antigens CNP, MBP, MOBP, MOG, and PLP (59%), HSP60 and HSP70 (38%), and the 68-kD neurofilament (3%). The antibody response in patients with MS was heterogeneous; CSF antibodies in individual patients reacted with different autoantigens. These autoantibodies were locally synthesized in the CNS and were of the immunoglobulin G class. Finally, we found that treatment with steroids decreased autoantibody reactivity, epitope spreading, and intrathecal autoantibody synthesis. Conclusions:These studies provide a new avenue to investigate the local antibody response in the CNS, which may serve as a biomarker to monitor both disease progression and response to therapy in MS. Neurology Antibodies and B cells play an important role in the pathogenesis of multiple sclerosis (MS).Clonally expanded B cells are found in the lesions and the CSF of patients with MS, 1 and B-cell follicles have been described in the meninges of patients with secondary progressive MS.2 These CNS-resident B cells have been linked to the production of intrathecal antibodies of restricted specificity, detectable as oligoclonal bands. 3,4 Antigen microarrays allow the high-throughput characterization of the antibody response using limited amounts of sample 5,6 with greater sensitivity than ELISA. 6,7 We and others have used antigen arrays to characterize the immune response in MS 7-9 and its experimental model experimental autoimmune encephalomyelitis, 9 -11 other autoimmune conditions, 5,12-15 tumors, 16 and healthy individuals. 17 In our studies on MS, we found patterns of serum antibody reactivity associated with different stages and pathologic subtypes of the disease.7 Moreover, the characterization of the serum antibody response in patients with MS led us to identify the Toll-like receptor-2/

show abstract

“…Although these arguments are indirect (6,8,9), they justify the intensive research devoted to the human T cell response against MBP over the past years. A key issue raised by these studies is the heterogeneity of the human T cell response to MBP.…”

Section: Introductionmentioning

confidence: 99%

Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones.

Meinl¹,

Weber²,

Drexler³

et al. 1993

J. Clin. Invest.

138

View full text Add to dashboard Cite

The human T cell response to the myelin basic protein (MBP) has been studied with respect to T cell receptor (TCR) peptide of which is currently being used in a clinical trial for treatment of MS patients, was expressed by only one of our TCL. However, within this complex pattern of MBP-specific T cell responses, a minority of MS patients were found to exhibit a more restricted response with respect to their TCL epitope specificity. In these patients 75-87% of the TCL responded to a single, patient-specific cluster of immunodominant T cell epitopes located within a small (20-amino acid) domain of MBP.These nested clusters of immunodominant epitopes were noted within the amino acids 80-105, 108-131, and 131-153. The T cell response to the immunodominant epitopes was not monoclonal, but heterogeneous, with respect to fine specificity, TCR usage, and even HLA restriction. In one patient (H.K.), this

show abstract

Antimyelin basic protein and antimyelin antibody‐producing cells in multiple sclerosis

Cited by 123 publications

References 22 publications

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Antigen microarrays identify CNS-produced autoantibodies in RRMS

Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones.

Contact Info

Product

Resources

About