Expression of CD5 on B lymphocytes correlates with disease activity in patients with multiple sclerosis

Seidi, Osheik; Semra, Y K; Sharief, Mohammed

doi:10.1016/s0165-5728(02)00360-0

Cited by 23 publications

(19 citation statements)

References 31 publications

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“…These mechanisms are consistent with prior studies that have demonstrated CNS persistence of mature B cells [17] and increased numbers of peripheral [18] and CSF [19] CD5 + B cells in MS patients with secondary progressive and active relapsing disease. However, their specific mechanistic relationship to the development and relative disease severity in MS is unclear and requires further characterization.…”

Section: Discussionsupporting

confidence: 92%

Epithelial V-Like Antigen Mediates Efficacy of Anti-Alpha4 Integrin Treatment in a Mouse Model of Multiple Sclerosis

et al. 2013

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Natalizumab inhibits the transmigration of activated T lymphocytes into the brain and is highly efficacious in multiple sclerosis (MS). However, from a pharmacogenomic perspective, its efficacy and safety in specific patients remain unclear. Here our goal was to analyze the effects of epithelial V-like antigen (EVA) on anti-alpha4 integrin (VLA4) efficacy in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). EVA has been previously characterized in human CD4 T lymphocytes, mouse thymic development, and choroid plexus epithelial cells. Further analysis here demonstrated expression in B lymphocytes and an increase in EVA+ lymphocytes following immunization. Following active induction of EAE using the MOG35–55 active immunization model, EVA deficient mice developed more severe EAE and white matter tissue injury as compared to wild type controls. This severe EAE phenotype did not respond to anti-VLA4 treatment. In both the control antibody and anti-VLA4 conditions, these mice demonstrated persistent CNS invasion of mature B lymphocyte (CD19+, CD21+, sIgG+), increased serum autoantibody levels, and extensive complement and IgG deposition within lesions containing CD5+IgG+ cells. Wild type mice treated with control antibody also demonstrated the presence of CD19+, CD21+, sIgG+ cells within the CNS during peak EAE disease severity and detectable serum autoantibody. In contrast, wild type mice treated with anti-VLA4 demonstrated reduced serum autoantibody levels as compared to wild type controls and EVA-knockout mice. As expected, anti-VLA4 treatment in wild type mice reduced the total numbers of all CNS mononuclear cells and markedly decreased CD4 T lymphocyte invasion. Treatment also reduced the frequency of CD19+, CD21+, sIgG+ cells in the CNS. These results suggest that anti-VLA4 treatment may reduce B lymphocyte associated autoimmunity in some individuals and that EVA expression is necessary for an optimal therapeutic response. We postulate that these findings could optimize the selection of treatment responders.

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Section: Discussionsupporting

confidence: 92%

Epithelial V-Like Antigen Mediates Efficacy of Anti-Alpha4 Integrin Treatment in a Mouse Model of Multiple Sclerosis

et al. 2013

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“…Increased CD5 + B cells also correlated with CSF CXCL13, which probably induced the CD5+ B cell migration into the central nervous system (CNS). 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: 91%

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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“…The proportion of CD3+, CD14+, or CD19+ cells within the CD45+ populations as well as the proportion of CD27+, CD27–, IgG+, and IgD+ cells within the CD19+ populations were determined. The proportions of CD3+CD45+ (range, 57 ± 3‐76 ± 7%) and CD19+CD45+ (range, 7 ± 1‐8 ± 5%) cells in thawed and fresh PBMNC samples prepared from WBF2 filters, and blood samples were comparable and in accordance to blood normal content 13,14 . Unexpectedly, the CD14+CD45+ population was almost undetectable within the thawed (<2 ± 1%) or fresh (<1 ± 1%) PBMNC populations recovered from filters.…”

Section: Resultsmentioning

confidence: 54%

Whole‐blood leukoreduction filters are a source for cryopreserved cells for phenotypic and functional investigations on peripheral blood lymphocytes

Néron¹,

Dussault²,

Racine³

2006

Transfusion

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Expression of CD5 on B lymphocytes correlates with disease activity in patients with multiple sclerosis

Cited by 23 publications

References 31 publications

Epithelial V-Like Antigen Mediates Efficacy of Anti-Alpha4 Integrin Treatment in a Mouse Model of Multiple Sclerosis

Epithelial V-Like Antigen Mediates Efficacy of Anti-Alpha4 Integrin Treatment in a Mouse Model of Multiple Sclerosis

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

Whole‐blood leukoreduction filters are a source for cryopreserved cells for phenotypic and functional investigations on peripheral blood lymphocytes

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