CEACAM1 mediates B cell aggregation in central nervous system autoimmunity.

B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1(+) B cells were present in brain infiltrates of MS patients.

The Correlation between the Virus- and Brain Antigen-Specific B Cell Response in the Blood of Patients with Multiple Sclerosis.

There is a largely divergent body of literature regarding the relationship between Epstein-Barr virus (EBV) infection and brain inflammation in multiple sclerosis (MS). Here, we tested MS patients during relapse (n = 11) and in remission (n = 19) in addition to n = 22 healthy controls to study the correlation between the EBV- and brain-specific B cell response in the blood by enzyme-linked immunospot (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). Cytomegalovirus (CMV) was used as a control antigen tested in n = 16 MS patients during relapse and in n = 35 patients in remission.

Categorization of multiple sclerosis relapse subtypes by B cell profiling in the blood.

Introduction: B cells are attracting increasing attention in the pathogenesis of multiple sclerosis (MS). B cell-targeted therapies with monoclonal antibodies or plasmapheresis have been shown to be successful in a subset of patients. Here, patients with either relapsing-remitting (n = 24) or secondary progressive (n = 6) MS presenting with an acute clinical relapse were screened for their B cell reactivity to brain antigens and were re-tested three to nine months later.

Therapeutic approaches to multiple sclerosis: an update on failed, interrupted, or inconclusive trials of neuroprotective and alternative treatment strategies.

Currently approved multiple sclerosis (MS) therapeutics have a mainly anti-inflammatory mode of action. However, a number of promising clinical trials have been initiated that either focus on neuroprotection or follow completely different treatment strategies. So far, all of these clinical trials have failed to show efficacy or had to be halted prematurely because of unexpected adverse events.

Therapeutic approaches to multiple sclerosis: an update on failed, interrupted, or inconclusive trials of immunomodulatory treatment strategies.

Multiple sclerosis (MS) continues to be a therapeutic challenge, and much effort is being made to develop new and more effective immune therapies. Particularly in the past decade, neuroimmunologic research has delivered new and highly effective therapeutic options, as seen in the growing number of immunotherapeutic agents and biologics in development. However, numerous promising clinical trials have failed to show efficacy or have had to be halted prematurely because of unexpected adverse events.

Heterozygous P0 deficiency protects mice from vincristine-induced polyneuropathy.

Patients with hereditary neuropathies are more susceptible to vincristine (VIN)-induced neuropathy than patients without this comorbidity. The heterozygous P0(+/-) mouse is an animal model of a distinct form of inherited neuropathies. These mice produce only 50% of the major myelin protein protein zero (P0) and display signs of demyelination in motor nerves at 4 months of age.

Altered expression of ion channel isoforms at the node of Ranvier in P0-deficient myelin mutants.

To elucidate the impact of myelinating Schwann cells on the molecular architecture of the node of Ranvier, we investigated the nodal expression of voltage-gated sodium channel (VGSC) isoforms and the localization of paranodal and juxtaparanodal membrane proteins in a severely affected Schwann cell mutant, the mouse deficient in myelin protein zero (P0). The abnormal myelin formation and compaction was associated with immature nodal cluster types of VGSC. Most strikingly, P0-deficient motor nerves displayed an ectopic nodal expression of the Na(v)1.