Main Role of Antibodies in Demyelination and Axonal Damage in Multiple Sclerosis

Muñoz, Úrsula; Sebal, Cristina; Escudero, Esther; Esiri, Margaret M.; Tzartos, John; Sloan, Carolyn; Sádaba, M. C.

doi:10.1007/s10571-021-01059-6

Cited by 17 publications

(19 citation statements)

References 66 publications

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“…When meningeal inflammation is not segregated by the presence of B cell aggregates in patients with SPMS, there is an inconsistent and weak correlation between the degree of meningeal immune cell infiltration and cortical demyelination, suggesting that B cell aggregates are the primary locations driving cortical demyelination 41 , 52 . Meningeal B cell aggregates may also be associated with demyelination in adjacent white matter 42 , 49 , 55 , 56 ; however, this relationship has not been found in all studies 52 , 54 .…”

Section: B Cells In Msmentioning

confidence: 84%

“…Meningeal and perivascular B cells are more numerous in RRMS and SPMS relative to PPMS, whereas plasma cells are more prevalent in progressive over RRMS 14 , 15 . B cells are more common in the parenchyma and perivascular spaces of active lesions relative to mixed active–inactive or inactive lesions whereas plasma cells are common in mixed active–inactive or inactive lesions 14 , 15 , 49 , 50 . Both B cells and plasma cells are rare in normal-appearing white matter 14 , 49 , 50 .…”

Section: B Cells In Msmentioning

confidence: 99%

“…B cells are more common in the parenchyma and perivascular spaces of active lesions relative to mixed active–inactive or inactive lesions whereas plasma cells are common in mixed active–inactive or inactive lesions 14 , 15 , 49 , 50 . Both B cells and plasma cells are rare in normal-appearing white matter 14 , 49 , 50 .…”

Section: B Cells In Msmentioning

confidence: 99%

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B cells in central nervous system disease: diversity, locations and pathophysiology

Jain

Yong

2021

Nat Rev Immunol

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B cells represent a relatively minor cell population within both the healthy and diseased central nervous system (CNS), yet they can have profound effects. This is emphasized in multiple sclerosis, in which B cell-depleting therapies are arguably the most efficacious treatment for the condition. In this Review, we discuss how B cells enter and persist in the CNS and how, in many neurological conditions, B cells concentrate within CNS barriers but are rarely found in the parenchyma. We highlight how B cells can contribute to CNS pathology through antibody secretion, antigen presentation and secretion of neurotoxic molecules, using examples from CNS tumours, CNS infections and autoimmune conditions such as neuromyelitis optica and, in particular, multiple sclerosis. Overall, understanding common and divergent principles of B cell accumulation and their effects within the CNS could offer new insights into treating these devastating neurological conditions.

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Section: B Cells In Msmentioning

confidence: 84%

Section: B Cells In Msmentioning

confidence: 99%

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B cells in central nervous system disease: diversity, locations and pathophysiology

Jain

Yong

2021

Nat Rev Immunol

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“…These patterns are stable within individual patients [ 38 ], and only pattern II shows antibody-mediated demyelination [ 37 , 39 ]. Both IgG and IgM localized on oligodendrocytes and axons, and they co-localized with complement and foamy macrophages [ 40 ]. With their multimeric structure, IgM antibodies are the strongest complement activator, which can cause more pronounced demyelination and axonal damage [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…Both IgG and IgM localized on oligodendrocytes and axons, and they co-localized with complement and foamy macrophages [ 40 ]. With their multimeric structure, IgM antibodies are the strongest complement activator, which can cause more pronounced demyelination and axonal damage [ 40 ]. A single bound IgM pentamer can trigger the classical pathway of complement activation and lyse a red blood cell.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis

et al. 2021

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The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.

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Ocrelizumab effect on humoral and cellular immunity in multiple sclerosis and its clinical correlates: a 3-year observational study

Capasso

Palladino²,

Cerbone

et al. 2022

J Neurol

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Objective We aim to evaluate 3-year effects of ocrelizumab (humanized anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS)) on lymphocytes, neutrophils and immunoglobulins: (1) when compared with pre-infusion assessment; (2) over the course of treatment; and (3) possible clinical correlates of the observed immunological modifications. Methods This real-world observational cohort study has been conducted on prospectively collected data from 78 MS patients (mean age 47.8 ± 10.5 years; females 48.7%) commencing on ocrelizumab from 2018, with mean follow-up of 36.5 ± 6.8 months. Clinical data and blood samples were collected every three months. Total lymphocyte count and subpopulations were assessed on peripheral blood using flow cytometry. Serum immunoglobulins were evaluated with nephelometry. Results When compared with pre-infusion values, we observed reduction of total, CD19 and CD20 lymphocyte counts; however, after the first infusion, their levels remained substantially stable. Over time we observed a progressive reduction of CD8 lymphocytes, while no changes were observed for CD4, CD27, CD3CD27, and CD19CD27. After the first infusion, we observed reduction in IgG, which further decreased during the follow-up. Higher probability of EDSS progression was associated with reduced modulation of CD8 lymphocytes. Interpretation Ocrelizumab affects both humoral and cellular immune responses. Disability progression over the follow-up was associated with lower CD8 cytotoxic T-lymphocyte reduction. Changes in humoral response are immediate and sustained, while modulation of cellular immunity occurs progressively through regular re-treatment, and is related to clinical stability.

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Main Role of Antibodies in Demyelination and Axonal Damage in Multiple Sclerosis

Cited by 17 publications

References 66 publications

B cells in central nervous system disease: diversity, locations and pathophysiology

B cells in central nervous system disease: diversity, locations and pathophysiology

Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis

Ocrelizumab effect on humoral and cellular immunity in multiple sclerosis and its clinical correlates: a 3-year observational study

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