Features of intrathecal immunoglobulins in patients with multiple sclerosis

Pauli, Franziska Di; Gredler, Viktoria; Kuenz, Bettina; Lutterotti, Andreas; Ehling, Rainer; Gneiss, Claudia; Schocke, Michael; Deisenhammer, Florian; Reindl, Markus; Berger, Thomas

doi:10.1016/j.jns.2009.09.016

Cited by 18 publications

(14 citation statements)

References 26 publications

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“…IgG subclass distribution is one of the important immunological characteristics of IgG and determination of the IgG subclass of some auto‐antibodies was reported to be important in understanding clinical features . For example, the main IgG subclasses of the antibodies were reported as follows: myasthenia gravis, IgG1, IgG3, and IgG4 ; Guillain–Barré syndrome, IgG1 and IgG3 ; multiple sclerosis, IgG1 and IgG3 ; neuromyelitis optica, IgG1 ; bullous pemphigoid, IgG1 and IgG4 ; and pemphigus vulgaris, IgG1 and IgG4 , respectively. There are some reports regarding the reduction ratio of IgG subclasses by IA .…”

Section: Discussionmentioning

confidence: 99%

Removal Characteristics of Immunoglobulin G Subclasses by Conventional Plasma Exchange and Selective Plasma Exchange

et al. 2015

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Selective plasma exchange (SePE) using a selective membrane separator is a modified method of simple plasma exchange (PE). Immunoglobulin G (IgG) subclass distribution is one of the important immunological characteristics of IgG. However, there is little information regarding the removal characteristics of IgG subclasses by SePE and conventional PE. Here, we investigated the removal ratio of IgG subclasses by PE and SePE in seven patients with immunological disorders. When the mean processed volume was 0.88 plasma volume (PV) (corresponding to 2.12 L), the mean percent reductions by PE were as follows: IgG, 63.2%; IgG1, 64.5%; IgG2, 64.0%; IgG3, 61.4%; and IgG4, 69.5%. When the mean processed volume was 1.18 PV (corresponding to 2.98 L), the mean percent reductions by SePE were as follows: IgG, 51.6%; IgG1, 55.3%; IgG2, 52.0%; IgG3, 53.7%; and IgG4, 64.6%. In both PE and SePE, using albumin solution as the supplementary fluid, IgG was effectively eliminated regardless of IgG subclasses.

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Section: Discussionmentioning

confidence: 99%

Removal Characteristics of Immunoglobulin G Subclasses by Conventional Plasma Exchange and Selective Plasma Exchange

et al. 2015

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“…The lack of statistical power, due to the low number of biological samples available for this study, led to a less than ideal statistical analysis, meaning that the reported p-values may not be directly associated to disease pathology. However, the reported unvalidated proteins are of significant biological interest, and among these are several immunoglobulin proteins, which have been previously reported to be elevated in CSF of MScl patients [18,19].…”

Section: Discussionmentioning

confidence: 99%

Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis

Stoop¹,

Singh²,

Dekker³

et al. 2010

PLoS ONE

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BackgroundBased on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85–90%) and primary progressive (PP) MScl (10–15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF proteins.Methodology/Principal FindingsCSF samples (n = 31) were handled according to the same protocol for quantitative mass spectrometry measurements we reported previously. In the comparison of PP MScl versus RR MScl we observed a number of differentially abundant proteins, such as protein jagged-1 and vitamin D-binding protein. Protein jagged-1 was over three times less abundant in PP MScl compared to RR MScl. Vitamin D-binding protein was only detected in the RR MScl samples. These two proteins were validated by independent techniques (western blot and ELISA) as differentially abundant in the comparison between both MScl types.Conclusions/SignificanceThe main finding of this comparative study is the observation that the proteome profiles of CSF in PP and RR MScl patients overlap to a large extent. Still, a number of differences could be observed. Protein jagged-1 is a ligand for multiple Notch receptors and involved in the mediation of Notch signaling. It is suggested in literature that the Notch pathway is involved in the remyelination of MScl lesions. Aberration of normal homeostasis of Vitamin D, of which approximately 90% is bound to vitamin D-binding protein, has been widely implicated in MScl for some years now. Vitamin D directly and indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and can prevent the development of autoimmune processes, and so it may be involved in neuroprotective elements in MScl.

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“…It has been long recognized that B cells are present in the MS central nervous system (CNS) [1], [2], including white matter lesions [3], [4], the normal appearing white matter [5], the cerebrospinal fluid (CSF) [6], [7], perivascular spaces in the CNS [3], and the CNS meninges [8]. In addition, clinical trial results with B cell depleting agents Rituximab and Ocrelizumab [9], [10] support a critical role for B-lymphocytes in MS pathology.…”

Section: Introductionmentioning

confidence: 99%

Secondary B Cell Receptor Diversification Is Necessary for T Cell Mediated Neuro-Inflammation during Experimental Autoimmune Encephalomyelitis

et al. 2013

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BackgroundClinical studies of B cell depletion in Multiple Sclerosis (MS) have revealed that B Lymphocytes are involved in the neuro-inflammatory process, yet it remains unclear how B cells can exert pro- and anti-inflammatory functions during MS. Experimental Autoimmune Encephalomyelitis (EAE) is an animal model of MS whereby myelin-specific T cells become activated and subsequently migrate to the Central Nervous System (CNS) where they perform pro-inflammatory functions such as cytokine secretion. Typically EAE is induced by immunization of mice of a susceptible genetic background with peptide antigen emulsified in Complete Freund's Adjuvant. However, novel roles for B-lymphocytes in EAE may also be explored by immunization with full-length myelin oligodendrocyte glycoprotein (MOG) that contains the B cell conformational epitope. Here we show that full length MOG immunization promotes a chronic disease in mice that depends on antigen-driven secondary diversification of the B cell receptor.MethodsActivation-Induced Deaminase (AID) is an enzyme that is essential for antigen-driven secondary diversification of the B cell receptor. We immunized AID−/− mice with the extracellular domain (amino acids 1–120) of recombinant human MOG protein (rhMOG) and examined the incidence and severity of disease in AID−/− versus wild type mice. Corresponding with these clinical measurements, we also evaluated parameters of T cell activation in the periphery and the CNS as well as the generation of anti-MOG antibodies (Ab).ConclusionsAID−/− mice exhibit reduced severity and incidence of EAE. This suggests that the secondary diversification of the B cell receptor is required for B cells to exert their full encephalogenic potential during rhMOG-induced EAE, and possibly also during MS.

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Features of intrathecal immunoglobulins in patients with multiple sclerosis

Cited by 18 publications

References 26 publications

Removal Characteristics of Immunoglobulin G Subclasses by Conventional Plasma Exchange and Selective Plasma Exchange

Removal Characteristics of Immunoglobulin G Subclasses by Conventional Plasma Exchange and Selective Plasma Exchange

Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis

Secondary B Cell Receptor Diversification Is Necessary for T Cell Mediated Neuro-Inflammation during Experimental Autoimmune Encephalomyelitis

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