Immunological mechanisms that associate with oligoclonal IgM band synthesis in multiple sclerosis

Villar, Luisa M.; Espiño, Mercedes; Cavanillas, María L.; Roldán, Ernesto; Urcelay, Elena; Concha, Emilio G. de la; Sádaba, María C.; Arroyo, Rafael; González-Porqué, Pedro; Álvarez‐Cermeño, José C.

doi:10.1016/j.clim.2010.06.007

Cited by 29 publications

(27 citation statements)

References 37 publications

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“…Elevated CD5+ expression on B lymphocytes was correlated with MS disease activity, number of gadolinium-enhancing lesions on MRI and was inversely correlated with disease duration (Seidi et al, 2002). Our data is in agreement with that of Villar et al (2010), who found higher CSF CXCL13 levels in patients with intrathecal IgM production, especially during relapses, than in patients without intrathecal IgM synthesis.…”

Section: Discussionsupporting

confidence: 95%

“…Complement activation can, in turn, cause extensive demyelination and axonal loss (Mead et al, 2002). Villar et al (2010) investigated the immunological mechanisms associated with intrathecal IgM production: they found a close correlation between IgM index and CSF CD5+ B cells, which are postulated to be responsible for intrathecal IgM synthesis. Increased CD5 + B cells also correlated with CSF CXCL13, which probably induced the CD5+ B cell migration into the central nervous system (CNS).…”

Section: Discussionmentioning

confidence: 98%

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Cerebrospinal fluid CXCL13 in clinically isolated syndrome patients: Association with oligoclonal IgM bands and prediction of Multiple Sclerosis diagnosis

Ferraro

Galli

Vitetta

et al. 2015

Journal of Neuroimmunology

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Cerebrospinal fluid (CSF) CXCL13 was shown to correlate with markers of intrathecal inflammation and CSF oligoclonal IgM bands (IgMOB) have been associated with a more severe Multiple Sclerosis (MS) course. We correlated CSF CXCL13 levels with clinical, MRI and CSF parameters, including CSF IgMOB, in 110 Clinically Isolated Syndrome (CIS) patients. CSF CXCL13 levels correlated with CSF cell count, total protein, IgG Index and with the presence of CSF IgGOB and IgMOB. CSF CXCL13 levels ≥15.4 pg/ml showed a good positive predictive value and specificity for a MS diagnosis and for a clinical relapse within one year from onset.

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Section: Discussionsupporting

confidence: 95%

Section: Discussionmentioning

confidence: 98%

Cerebrospinal fluid CXCL13 in clinically isolated syndrome patients: Association with oligoclonal IgM bands and prediction of Multiple Sclerosis diagnosis

Ferraro

Galli

Vitetta

et al. 2015

Journal of Neuroimmunology

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“…In addition, the combined determination of CXCL13, IL-8 and IL12-p40 in CSF establishes the presence of active inflammation in CNS [29]. Also, in MS patients with IgM OCB against myelin lipids, the course of disease will be characterized by earlier occurrence and increased frequency of relapses, earlier progression toward disability, and increment of percentage of CD5 + B-cell population in peripheral blood and, remarkably, in CSF [30,31]. Two additional CSF biomarkers include soluble CD27 (sCD27) which is considered an excellent biomarker of T-cell-mediated active intrathecal inflammation in patients with progressive MS [32] and the light chain subunit of neurofilaments (NfL) which is a reliable biomarker of axonal damage [33].…”

Section: Biomarkersmentioning

confidence: 99%

Autologous Bone Marrow Transplantation in Multiple Sclerosis: Biomarker Relevance for Patient Recruitment and Follow up

Londoño

Mora

2016

J Clin Cell Immunol

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BackgroundDespite the current availability of disease modifying therapies for the treatment of multiple sclerosis, there are still patients who suffer from severe neurological dysfunction in the relapsing-remitting or early progressive forms of the disease. For these patients autologous hematopoietic stem cell transplant offers an important therapeutic solution to prevent progression to irreversible disability. In spite of multiple studies in the last two decades, patient inclusion criteria, protocols for peripheral blood stem cell mobilization and bone marrow cell conditioning and methodology of follow up for autologous hematopoietic stem cell transplant in multiple sclerosis have not been strictly unified.MethodsWe reviewed five recent clinical studies that confirmed the positive outcome of transplant in spite of disclosing significant differences in methodology of enrollment including patient disease subtypes, disease duration range, disability, regimens of peripheral blood stem cell mobilization and bone marrow cell conditioning, scheduling of imaging studies after transplant, and absence of laboratory biomarkers consistently applied to these studies.ResultsTherapy with autologous hematopoietic stem cell transplant has shown best results among young individuals with severe relapsing-remitting or early progressive disease through its ability to maintain no evidence of disease activity status in a significantly higher proportion of patients after transplant in comparison to patients treated with disease modifying therapies. Important cross-sectional differences in the reviewed studies were found.ConclusionA specific and careful selection of biomarkers, based on the current physiopathological mechanisms known to result in multiple sclerosis, will contribute to a better and earlier patient selection for autologous hematopoietic stem cell transplant and follow up process. An objective and measurable response could be obtained with the determination of biomarkers at the onset of treatment and after follow-up on reconstitution of the immune response. The application of such parameters could also help further our understanding of pathogenesis of the disease.

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“…These authors found that increased levels of IgM OCBs reactive with lipids, mostly phosphatidylcholine, were associated with increased numbers of CD19+ CD5+ B cells in the CNS, and a more aggressive disease course (Villar et al, 2005; Thangarajh et al, 2008). Recently, the same group has reported that the production of lipid-reactive IgM OCBs correlates with the recruitment of CD19+ CD5+ B cells to the CNS by a CXCL13-dependent mechanism triggered by TNFα (Villar et al, 2010). The pathogenic processes controlling the activation and recruitment of CD19+ CD5+ B cells to the CNS in MS seem to be heterogeneous, as lipid reactive IgM OCBs are associated to RRMS and SPMS, but not to PPMS (Villar et al, 2009).…”

Section: Antibody Response To Lipids As a Biomarker For Msmentioning

confidence: 99%

Lipids and lipid-reactive antibodies as biomarkers for multiple sclerosis

Quintana

Yeste

Weiner

et al. 2012

Journal of Neuroimmunology

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Multiple sclerosis (MS) is an autoimmune disease that targets the central nervous system (CNS). MS initially follows a relapsing–remitting course (RRMS) in which acute attacks are followed by a complete recovery. Eventually, 65% of the RRMS patients go on to develop secondary progressive MS (SPMS), characterized by the progressive and irreversible accumulation of neurological disability. It has been proposed that the transition from RRMS to SPMS results from changes in the nature of the inflammatory response and the progressive accumulation of neurodegeneration. To date, however, there is no reliable method to monitor the activity of the different immune and neurodegenerative processes that contribute to MS pathology. Thus, there is a need for biomarkers useful for the diagnosis, treatment and monitoring of MS patients. In this review, we discuss the potential use of lipids and the immune response against them as biomarkers of inflammation and neuro-degeneration for MS.

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Immunological mechanisms that associate with oligoclonal IgM band synthesis in multiple sclerosis

Cited by 29 publications

References 37 publications

Cerebrospinal fluid CXCL13 in clinically isolated syndrome patients: Association with oligoclonal IgM bands and prediction of Multiple Sclerosis diagnosis

Cerebrospinal fluid CXCL13 in clinically isolated syndrome patients: Association with oligoclonal IgM bands and prediction of Multiple Sclerosis diagnosis

Autologous Bone Marrow Transplantation in Multiple Sclerosis: Biomarker Relevance for Patient Recruitment and Follow up

Lipids and lipid-reactive antibodies as biomarkers for multiple sclerosis

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