Immunoglobulin <scp>M</scp> oligoclonal bands: Biomarker of targetable inflammation in primary progressive multiple sclerosis

Villar, Luisa M.; Casanova, Bonaventura; Ouamara, Nadia; Comabella, Manuel; Jalili, Farzaneh; Leppert, David; Andrés, Clara de; Izquierdo, Guillermo; Arroyo, Rafael; Avşar, Timuçin; Лапин, С. В.; Johnson, Trina; Montalbán, Xavier; Fernández, Óscar; Álvarez‐Lafuente, Roberto; Masterman, Donna; García-Sánchez, M. I.; Coret, Francisco; Síva, Aksel; Evdoshenko, Evgeniy; Álvarez‐Cermeño, José C.; Bar‐Or, Amit

doi:10.1002/ana.24190

Cited by 54 publications

(35 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although MS is generally considered a T-cell mediated disease, B-cells populate the demyelinating lesions and the cerebrospinal fluid (CSF) and form lymphoid follicles in the brain parenchyma and the meninges[3]. Importantly, the presence of oligoclonal bands in the CSF, the most frequently observed lab abnormality, is useful for diagnosis and MS conversion risk stratification[4,5]. Moreover, B-cell depletion has proven an effective treatment for MS, suggesting B-cells play a central role in the pathogenesis of MS [6].…”

Section: Introductionmentioning

confidence: 99%

Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique approach and systematic review

et al. 2017

View full text Add to dashboard Cite

IntroductionAntibodies targeting the inward-rectifying potassium channel KIR4.1 have been associated with multiple sclerosis (MS) but studies using diverse techniques have failed to replicate this association. The detection of these antibodies is challenging; KIR4.1 glycosylation patterns and the use of diverse technical approaches may account for the disparity of results. We aimed to replicate the association using three different approaches to overcome the technical limitations of a single technique. We also performed a systematic review to examine the association of anti-KIR4.1 antibodies with MS.MethodsSerum samples from patients with MS (n = 108) and controls (n = 77) were tested for the presence of anti-KIR4.1 antibodies using three methods: 1) by ELISA with the low-glycosylated fraction of recombinant KIR4.1 purified from transfected HEK293 cells according to original protocols; 2) by immunocytochemistry using KIR4.1-transfected HEK293 cells; and 3) by immunocytochemistry using the KIR4.1.-transfected MO3.13 oligodendrocyte cell line. We developed a systematic review and meta-analysis of the association of anti-KIR4.1 antibodies with MS according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsWe did not detect anti-KIR4.1 antibodies in the MS patients or in controls using ELISA. Neither did we detect any significant reactivity against the antigen on the cell surface using the KIR4.1-transfected HEK293 cells or the KIR4.1-transfected MO3.13 cells. We included 13 prospective controlled studies in the systematic review. Only three studies showed a positive association between anti-KIR4.1 and MS. Clinical and statistical heterogeneity between studies precluded meta-analysis of their results.ConclusionWe found no association between anti-KIR4.1 antibody positivity and MS. Although this lack of replication may be due to technical limitations, evidence from our study and others is mounting against the role of KIR4.1 as a relevant MS autoantigen.

show abstract

Section: Introductionmentioning

confidence: 99%

Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique approach and systematic review

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In the Table 6 we organize the MS patients paying attention to data we obtained in which the presence of CSF-restricted IgM OCB was associated with an active inflammatory disease phenotype in PPMS patients with more active inflammatory disease (Villar et al, 2014). With this working classification, we found significant differences in the age at beginning between PPMS and the other two MS forms (RRMS and SPMS) ( p < 0.003) ( Table 6 ).…”

Section: Resultsmentioning

confidence: 99%

Bioenergetic Failure in Rat Oligodendrocyte Progenitor Cells Treated with Cerebrospinal Fluid Derived from Multiple Sclerosis Patients

Mathur

Riffo‐Campos

Castillo

et al. 2017

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

In relapsing-remitting multiple sclerosis (RRMS) subtype, the patient’s brain itself is capable of repairing the damage, remyelinating the axon and recovering the neurological function. Cerebrospinal fluid (CSF) is in close proximity with brain parenchyma and contains a host of proteins and other molecules, which influence the cellular physiology, that may balance damage and repair of neurons and glial cells. The purpose of this study was to determine the pathophysiological mechanisms underpinning myelin repair in distinct clinical forms of MS and neuromyelitis optica (NMO) patients by studying the effect of diseased CSF on glucose metabolism and ATP synthesis. A cellular model with primary cultures of oligodendrocyte progenitor cells (OPCs) from rat cerebrum was employed, and cells were treated with CSF from distinct clinical forms of MS, NMO patients and neurological controls. Prior to comprehending mechanisms underlying myelin repair, we determine the best stably expressed reference genes in our experimental condition to accurately normalize our target mRNA transcripts. The GeNorm and NormFinder algorithms showed that mitochondrial ribosomal protein (Mrpl19), hypoxanthine guanine phosphoribosyl transferase (Hprt), microglobulin β2 (B2m), and transferrin receptor (Tfrc) were identified as the best reference genes in OPCs treated with MS subjects and were used for normalizing gene transcripts. The main findings on microarray gene expression profiling analysis on CSF treated OPCs cells revealed a disturbed carbohydrate metabolism and ATP synthesis in MS and NMO derived CSF treated OPCs. In addition, using STRING program, we investigate whether gene–gene interaction affected the whole network in our experimental conditions. Our findings revealed downregulated expression of genes involved in carbohydrate metabolism, and that glucose metabolism impairment and reduced ATP availability for cellular damage repair clearly differentiate more benign forms from the most aggressive forms and worst prognosis in MS patients.

show abstract

mentioning

confidence: 99%

“…[13][14][15] In addition, they show higher B-cell counts in CSF. 15 Because many patients with IgM bands in CSF respond suboptimally to immunomodulatory treatments, 16 a high percentage of them end up being treated with natalizumab. 17 In the present study, we aimed to examine whether presence of CSF IgM bands, as a marker of increased inflammatory CNS disease activity, might contribute to the stratification of PML risk and to assess the relationship of these antibodies with the numbers and profile of T cells present in the CSF.…”

mentioning

confidence: 99%

Lipid‐specific immunoglobulin M bands in cerebrospinal fluid are associated with a reduced risk of developing progressive multifocal leukoencephalopathy during treatment with natalizumab

Villar

Costa‐Frossard

Masterman

et al. 2015

Annals of Neurology

Self Cite

View full text Add to dashboard Cite

show abstract

Immunoglobulin M oligoclonal bands: Biomarker of targetable inflammation in primary progressive multiple sclerosis

Abstract: The presence of CSF IgM OCB may be a biomarker for a subset of PPMS patients with more active inflammatory disease, who may benefit from immune-directed treatments.

Cited by 54 publications

References 34 publications

Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique approach and systematic review

Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique approach and systematic review

Bioenergetic Failure in Rat Oligodendrocyte Progenitor Cells Treated with Cerebrospinal Fluid Derived from Multiple Sclerosis Patients

Lipid‐specific immunoglobulin M bands in cerebrospinal fluid are associated with a reduced risk of developing progressive multifocal leukoencephalopathy during treatment with natalizumab

Contact Info

Product

Resources

About