Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions

O’Connor, Kevin; Chitnis, Tanuja; Griffin, Diane E.; Piyasirisilp, Sucheep; Bar‐Or, Amit; Khoury, Samia J.; Wucherpfennig, Kai W.; Hafler, David A.

doi:10.1016/s0165-5728(03)00002-x

Cited by 93 publications

(62 citation statements)

References 42 publications

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“…More recently, O'Connor et al (55) attempted to characterize the affinity of anti-MBP antibodies in serum and CSF of MS patients using a solution-phase radioimmunoassay, which is less likely to detect low-affinity antibody/antigen interactions that might be due to excess antigen fixed to a plate or multimeric presentation in a solid-phase ELISA; they only detected autoantibodies to MBP by ELISA, suggesting that moderate-or high-affinity antibodies against MBP were not expressed in MS patients. The detection of low-affinity or low-level anti-MBP antibodies in MS is consistent with other studies that failed to detect anti-MBP antibodies in the CSF by various methods (56,57).…”

Section: Myelin Basic Protein-mentioning

confidence: 98%

B cells in multiple sclerosis

Mark¹

2004

Front Biosci

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The most common laboratory abnormality in multiple sclerosis (MS) is an increased amount of cerebrospinal fluid IgG and the presence of oligoclonal bands. Despite studies of the humoral response that suggest the involvement of an infectious agent or autoantigen in disease, the major targets of the oligoclonal response are still unknown. Identification of these targets will reveal valuable insights into the cause and pathogenesis of MS and is likely to lead to effective treatment.

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Section: Myelin Basic Protein-mentioning

confidence: 98%

B cells in multiple sclerosis

Mark¹

2004

Front Biosci

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“…For the same reason, it is difficult to compare the characteristics and the relevance of anti-MBP antibodies in EAE and MS. Some researchers have shown that autoantibodies against native human MBP have low binding affinities, that they are relatively infrequent in MS (50) and that they are found in sera of healthy individuals as well (51).…”

Section: Figmentioning

confidence: 99%

High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients

Hecker

Fitzner

Wendt

et al. 2016

Molecular & Cellular Proteomics

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Intrathecal immunoglobulin G (IgG Multiple sclerosis (MS)1 is a chronic disease of the central nervous system (CNS) that typically affects young adults, especially women. The disease is characterized by discrete areas of inflammation (lesions), demyelination, axonal loss, and astrogliosis in the brain and spinal cord. The clinical correlate of these processes is a wide range of neurological signs and symptoms involving mobility problems, vision problems, cognitive dysfunction, fatigue, and pain (1, 2). This

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“…M125-A2, the heavy chain edited clone member of M125-A, had negligible MBP binding according to this assay. Serum IgG from a patient with RRMS that has very little MBP reactivity (O'Connor et al, 2003) and serum IgG from a patient with Viral Encephalomyelitis with known high affinity MBP reactivity (Panel 6A) (O'Connor et al, 2003) were included as internal controls. Comparing MBP reactivity of serum IgG to these engineered Fabs is invalid for the same reasons given when using the full-length anti-MBP IgG antibody in the ELISA assays (differences in detection strategy and avidity).…”

Section: Confirmation Of Fab Binding By Solid Phase Dissociation Enhamentioning

confidence: 99%

Antigen specificity of clonally expanded and receptor edited cerebrospinal fluid B cells from patients with relapsing remitting MS

Lambracht-Washington

O’Connor

Cameron

et al. 2007

Journal of Neuroimmunology

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We re-engineered the immunoglobulin rearrangements from clonally expanded CSF B cells of three Multiple Sclerosis patients as Fab fragments, and used three methods to test for their Ag-specificity. Nine out of ten Fab fragments were reactive to Myelin Basic Protein (MBP). The one Fab that did not react to MBP was a product of receptor editing. Two of the nine MBP-reactive Fabs were also reactive to GFAP and CNPase, indicating that these clones were polyreactive. Targeting the mechanisms that allows these self-reactive B cells to reside in the CSF of MS patients may prove to be a potent immunotherapeutic strategy.

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Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions

Cited by 93 publications

References 42 publications

B cells in multiple sclerosis

B cells in multiple sclerosis

High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients

Antigen specificity of clonally expanded and receptor edited cerebrospinal fluid B cells from patients with relapsing remitting MS

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