Intrathecal IgM synthesis in neurologic diseases: Relationship with disability in MS

Villar, Luisa M.; Masjuán, Jaime; González-Porqué, Pedro; Plaza, J. Miquel; Sádaba, M. C.; Roldán, Ernesto; Bootello, A; Alvarez‐Cermeño, J. C.

doi:10.1212/wnl.58.5.824

Cited by 86 publications

(68 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The presence of CSF-restricted OCMBs seems to be characteristic of these MS patients throughout the course of the disease (13,14) and is associated with a more aggressive disease course (11,12,14). Sustained IgM responses like this are usually produced by the long-lived CD5 + subset of B lymphocytes (19), which is increased in CSF of patients with aggressive forms of MS (21).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS

Villar¹,

Sádaba²,

Roldán³

et al. 2005

J. Clin. Invest.

235

129

View full text Add to dashboard Cite

Oligoclonal IgM bands restricted to cerebrospinal fluid are an unfavorable prognostic marker in MS, the most common demyelinating disease of the CNS. We have attempted to identify the B cell subpopulation responsible for oligoclonal IgM secretion and the specificity of these bands. In addition, we explored the relationship between specificity and disease evolution. Intrathecal B cell subpopulations present in 29 MS patients with oligoclonal IgM bands and 52 without them were analyzed. A considerable increase in CD5 + B lymphocytes was found in patients with oligoclonal IgM bands. These cells mostly secrete IgM antibodies recognizing nonproteic molecules. We also studied whether oligoclonal IgM bands present in cerebrospinal fluid of 53 MS patients were directed against myelin lipids. This was the case in most patients, with phosphatidylcholine being the most frequently recognized lipid. Disease course of 15 patients with oligoclonal IgM against myelin lipids and 33 patients lacking them was followed. Patients with anti-lipid IgM suffered a second relapse earlier, had more relapses, and showed increased disability compared with those without anti-lipid IgM. The presence of intrathecal anti-myelin lipid IgM antibodies is therefore a very accurate predictor of aggressive evolution in MS.

show abstract

Section: Discussionmentioning

confidence: 99%

“…With this method, intrathecal IgM synthesis has been detected in a subgroup of MS patients (11,12). These IgM bands usually persist in MS patients throughout the course of the disease (13,14) and are an unfavorable prognostic marker (14).…”

Section: Ms Is a Demyelinating Disease Of The Cns Of Unknown Etiologymentioning

confidence: 99%

Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS

Villar¹,

Sádaba²,

Roldán³

et al. 2005

J. Clin. Invest.

235

129

View full text Add to dashboard Cite

show abstract

“…Immunohistologic studies indicate immune effector functions for plaque IgG (3)(4)(5)(6)(7) and MS patients with a high B cell-to-monocyte ratio in cerebrospinal fluid (CeSF) show a more rapid disease progression (8). Oligoclonal IgM bands are also present in CeSF of some MS patients and correlate with a more aggressive form of disease (9,10). Phenotypic analyses of B cell subsets and sequence analyses of Ig V regions expressed by B and plasma cells in MS CeSF and brain indicate a T cell-dependent Ag-specific response (reviewed in Ref.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

VH4 Gene Segments Dominate the Intrathecal Humoral Immune Response in Multiple Sclerosis

Owens

Winges²,

Ritchie³

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

A characteristic feature of the CNS inflammatory response in multiple sclerosis (MS) is the intrathecal synthesis of IgG and the presence of oligoclonal bands. A strong correlation between CD138+ plasma blast numbers in MS cerebrospinal fluid (CeSF) and intrathecal IgG synthesis suggests that these cells are the major Ab-secreting cell type in MS CeSF. Sequencing of V regions from CD138+ cells in MS CeSF has revealed somatically mutated and expanded IgG clonotypes consistent with an Ag-targeted response. In the present study, single-cell RT-PCR analysis of CD138+ cells from 11 MS patients representing differing clinical courses and stages of disease identified expansion of CD138+ cells with functionally rearranged VH4 gene segments as an overriding feature of MS CeSF repertoires. VH4 dominance was attributed to the preferential selection of specific VH4 genes, particularly gene segment VH4-39, which displayed a significant enrichment in CeSF compared with MS peripheral blood B cells. A modest increase in VH4 prevalence among MS peripheral blood IgG memory cells was also noted, suggesting that factors shaping the CD138 repertoire in CeSF might also influence the peripheral IgG memory cell pool. These results indicate a highly restricted B cell response in MS. Identifying the targets of CeSF plasma cells may yield insights into disease pathogenesis.

show abstract

“…Elevated intrathecal Ig has been associated with poorer MS prognosis (44,45) . In particular, anti-lipid IgM is associated with enhanced early disease activity and worse prognosis (46) . The advent of rituximab, a monoclonal antibody therapy that specifi cally lyses B cells, confi rmed the key role of B cells and their products in MS. Rituximab targets CD20, a cell surface molecule confi ned to B cells, leading to depletion of circulating B cell.…”

Section: Cd4mentioning

confidence: 99%

Update on multiple sclerosis, its diagnosis and treatments

Cross

Piccio

2012

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a central nervous system disorder, characterized by mononuclear cell infl ammation, demyelination and often with extensive axonal injury. It was fi rst described neuropathologically in the late 1800s. MS has an interesting geographical epidemiology, with a higher rate at latitudes further from the equator in both directions. Women outnumber males by about 2:1; this ratio has been increasing in recent years. Genome wide association studies have thus far identifi ed over 50 genetic susceptibility loci, and these are rapidly expanding. Several environmental risk factors have been identifi ed, including low serum vitamin D levels, exposure to Epstein-Barr virus and cigarette smoking. MS displays a heterogeneous disease course; most patients with the disease begin with a relapsing-remitting course, but often eventually develop steady disability progression. A small percentage of MS patients have a progressive course without clinical relapses. Several treatments are now available to decrease relapse rate and slow the accumulation of disability in patients with relapsing MS, but there is currently no effective treatment to slow the progressive forms of MS.

show abstract

Intrathecal IgM synthesis in neurologic diseases: Relationship with disability in MS

Cited by 86 publications

References 10 publications

Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS

Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS

VH4 Gene Segments Dominate the Intrathecal Humoral Immune Response in Multiple Sclerosis

Update on multiple sclerosis, its diagnosis and treatments

Contact Info

Product

Resources

About