Relation between benign course of multiple sclerosis and low-grade humoral immune response in cerebrospinal fluid.

Stendahl-Brodin, Lena; Link, Hans

doi:10.1136/jnnp.43.2.102

Cited by 73 publications

(42 citation statements)

References 16 publications

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“…Thirdly, activation of B cells could be a random bystander effect of the inflammatory response observed in MS lesions [91]. Fourthly, Ab response may be triggered by B cell superantigens stimulation [161]. Lastly, hypermutable areas of the genome during viral infections may activate transcription, producing neoantigens [22,112].…”

Section: S B Cell Responses In Msmentioning

confidence: 99%

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Oligoclonal bands and antibody responses in Multiple Sclerosis

Correale

Molinas²

2002

J Neurol

105

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Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System with multifocal areas of demyelination. Although its etiology and pathogenesis remain controversial, several lines of evidence indicate that MS is mediated by a misdirected immune response against one or several myelin proteins. The involvement of diverse leukocyte subsets and their products in MS is still the subject of considerable debate. The emphasis on T cells has derived mainly from the detection of activated T cells in MS plaques and analogies with animal models of MS. Because of these observations cell-mediated immunity has dominated the research field of MS to this day. However, in recent years the role of B cells, plasma cells and immunoglobulins in MS have been re-examined, and current findings indicate that humoral immunity also plays a major role in disease pathogenesis. B cells and their products could exert several potential effects during the course of MS. Firstly, autoantibodies against specific myelin antigens could mediate damage to myelin membranes. Secondly, some studies suggest that natural autoantibodies could enhance remyelination. Thirdly, antibodies directed against myelin components can participate in anti-idiotypic networks, which may regulate the course of MS. Increased intrathecal immunoglobulin synthesis reflected by raised IgG indices and an oligoclonal pattern is the most common abnormality detected in MS patients. The introduction of more sensitive procedures for protein detection has allowed demonstrating oligoclonal bands (OCBs) in up to 95 % of patients with clinically definite MS. Although the presence of OCBs in CSF of MS patients is now well established as a sensitive laboratory test to support the clinical diagnosis, OCBs may be present in other disorders, including those not directly related to infection or abnormal immune response. Nevertheless, the pathogenesis of OCBs in MS is still obscure, and despite extensive research their antigenic target(s) have yet to be established. Therefore, a critical task is to identify the specificity of such target(s), thus providing significant clues about MS etiology. For this purpose, novel molecular immunologic strategies have been recently developed to offer alternative approaches to identify putative antigens recognized by antibodies present in MS patients. The elucidation of the mechanisms and target(s) responsible for the onset of MS has obvious implications for the further development of specific therapies.

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Section: S B Cell Responses In Msmentioning

confidence: 99%

“…Secondly, Ab production may be driven by cross-reactivity with infectious agents (molecular mimicry) [161,190]. Thirdly, activation of B cells could be a random bystander effect of the inflammatory response observed in MS lesions [91].…”

Section: S B Cell Responses In Msmentioning

confidence: 99%

Oligoclonal bands and antibody responses in Multiple Sclerosis

Correale

Molinas²

2002

J Neurol

105

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“…On the other hand, there are various methods for detecting OCBs; thus, the sensitivity of the methods used by different laboratories may cause significant differences [31] . However, previous studies have demonstrated the prognostic significance of OCBs, while a benign course of MS was reported to be associated with the absence of OCB [5,6] .…”

Section: Discussionmentioning

confidence: 97%

“…However, IgG synthesis in the cerebrospinal fluid (CSF) is revealed as oligoclonal bands (OCBs) [4] . Previous studies suggested the prognostic importance of OCBs, as the absence of OCBs predicted a relatively be-nign course of MS and less disability [5][6][7] . It has also been shown that patients with fewer OCBs appeared to have lower numbers of active plaques and plasma cells in white matter and the meninges [8] .…”

Section: Introductionmentioning

confidence: 99%

CD24 Gene Allele Variation Is Not Associated with Oligoclonal IgG Bands and IgG Index of Multiple Sclerosis Patients

Saadatnia

Najafi²,

Najafi³

et al. 2012

Neuroimmunomodulation

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Objective: Multiple sclerosis (MS) shows evidence of many distinctive aspects of an autoimmune disorder, including a polygenic inheritance. A recent candidate gene for susceptibility to MS is CD24, which has also been shown to be associated with disease progression. This study was designed to examine whether there is a relationship between the CD24 genotype, oligoclonal band (OCB) status and IgG index in the cerebrospinal fluid (CSF) of MS patients. Methods: A total of 27 definite MS patients were enrolled in this cross-sectional study. Blood samples were collected from a peripheral vein, and CSF was obtained by lumbar puncture. The CD24 gene was sequenced in the blood specimen, and albumin and IgG concentrations were measured in both CSF and serum. We compared both IgG index and OCB status in patients with and without CD24V/V. The correlation between MS severity score (MSSS), OCB status, CD24 genotype and IgG index was studied. Results: Only 15 patients were OCB positive. Among patients with negative OCBs, only 2 patients had the V/V genotype. Furthermore, in those with the V/V genotype, IgG index was not significantly elevated (p = 0.322). Patients with the V/V genotype had a significantly higher MSSS (p = 0. 04), but neither the presence of OCBs nor the IgG index showed significant correlation with MSSS (p = 0.379 and 0.20, respectively). Conclusion: We could not show any relationship between the CD24V/V genotype, OCB status and IgG index. This could be interpreted as indicating that the CD24V/V allele exerts its effects on the disease course independently of CSF IgG synthesis.

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“…True OCB-negative COMPARISON 8 The lack of OCBs in patients with confirmed MS suggests a better prognosis related to the less pronounced humoral immune response. 9 Isoelectric focusing has been shown to be the most sensitive technique for detecting OCBs. 10 Many laboratories have incorporated isoelectric focusing for detecting OCBs, and as a result, most reported improved sensitivities when using this technology.…”

Section: Discussionmentioning

confidence: 99%