The intrathecal synthesis of virus-specific oligoclonal IgG in multiple sclerosis

Sindic, Christian; Monteyne, Philippe; Laterre, Emile-Christian

doi:10.1016/0165-5728(94)90233-x

Cited by 109 publications

(67 citation statements)

References 23 publications

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“…Virus-specific ASC are detected in the lymphoid tissues prior to the CNS [16], similar to findings for T cells [30]. Consistent with their derivation from secondary lymphoid organ [14,[51][52][53]. Although a small frequency of oligoclonal Ab in the CSF of MS patients are specific for Ag associated with viral infections acquired as young adults, the majority have as-yet-undefined specificities [18].…”

mentioning

confidence: 67%

“…Consistent with their derivation from secondary lymphoid organ germinal centers, virus-specific ASC in the CNS emerge subsequent to germinal center reactions, which peak *12 days p.i. [4,6] [51][52][53]. Although a small frequency of oligoclonal Ab in the CSF of MS patients are specific for Ag associated with viral infections acquired as young adults, the majority have as-yet-undefined specificities [18].…”

Section: Discussionmentioning

confidence: 99%

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CNS viral infection diverts homing of antibody‐secreting cells from lymphoid organs to the CNS

et al. 2006

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Neurotropic coronavirus infection of mice results in acute encephalomyelitis followed by viral persistence. Whereas cellular immunity controls acute infection, humoral immunity regulates central nervous system (CNS) persistence. Maintenance of serum Ab was correlated with tissue distribution of virus-specific Ab-secreting cells (ASC). Although virus-specific ASC declined in cervical lymph node and spleen after infectious virus clearance, virus-specific serum Ab was sustained at steady levels, with a delay in neutralizing Ab. Virus-specific ASC within the CNS peaked rapidly 1 wk after control of infectious virus and were retained throughout chronic infection, consistent with intrathecal Ab synthesis. Surprisingly, frequencies of ASC in the BM remained low and only increased gradually. Nevertheless, virus-specific ASC induced by peripheral infection localized to both spleen and BM. The data suggest that CNS infection provides strong stimuli to recruit ASC into the inflamed tissue through sustained up-regulation of the CXCR3 ligands CXCL9 and CXCL10. Irrespective of Ag deprivation, CNS retention of ASC coincided with elevated BAFF expression and ongoing differentiation of class II + to class II -CD138 + CD19 + plasmablasts. These results confirm the CNS as a major ASCsupporting environment, even after resolution of viral infection and in the absence of chronic ongoing inflammation. IntroductionThe preeminent goal of the immune system is to eliminate pathogens and establish immunological memory [1]. Both T cells and Ab participate in eliminating a variety of pathogens; however, sustained serum Ab is an important criteria for many vaccination strategies, as they provide the first line of defense against re-infection [2]. Upon Ag encounter in regional lymph nodes, B cells undergo clonal expansion in extrafollicular foci and within germinal centers [3,4].Rapidly activated B cells secrete low-affinity Ab but can undergo isotype switching and limited BCR hypermutation as they differentiate into plasmablasts [3]. In the milieu of accessory cells and cytokines, germinal center B cells undergo affinity maturation and ultimately differentiate into both Ab-secreting cells (ASC) and memory B cells. As Ag is depleted, ASC and memory B cells are detected with increasing frequency in BM [2], where both stromal cells and other resident cells provide soluble as well as contact-dependent survival signals, including CXCL12 and BAFF [5]. Ab secretion by terminally differentiated plasma cells is independent of both Ag and T cell regulation [2,6]. Long-lived ASC in BM and spleen maintain serum Ab, thus providing protective immunity to re-infection, sometimes for the [4,6]. In contrast to Ag encountered in the periphery, the regulation of B cell activation by Ag sequestered within the central nervous system (CNS) is less clear. The absence of dedicated lymphatic drainage and the presence of the blood brain barrier (BBB) limits Ag transport from the CNS into secondary lymphoid tissue as well as trafficking of both cells and macromolecule...

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confidence: 67%

Section: Discussionmentioning

confidence: 99%

CNS viral infection diverts homing of antibody‐secreting cells from lymphoid organs to the CNS

et al. 2006

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“…Some investigators have attributed this pattern of IgG expression in MS brain and the apparent absence of OGB specificity to non-specific or bystander-activation of B cells randomly recruited into the CNS (110). However, the somatic mutation and repertoire shifts that occur in antibodies after repeated exposure to antigen might also produce the different OGB profiles.…”

Section: Characterization Of the B Cell Responsementioning

confidence: 99%

B cells in multiple sclerosis

Mark¹

2004

Front Biosci

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The most common laboratory abnormality in multiple sclerosis (MS) is an increased amount of cerebrospinal fluid IgG and the presence of oligoclonal bands. Despite studies of the humoral response that suggest the involvement of an infectious agent or autoantigen in disease, the major targets of the oligoclonal response are still unknown. Identification of these targets will reveal valuable insights into the cause and pathogenesis of MS and is likely to lead to effective treatment.

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“…The individual antibody species can also be shown as part of the oligoclonal bands in cerebrospinal fluid (CSF) 15 . The measles-, rubella-, varicella zoster-antibodies have a much higher frequency compared to the other antibody species analyzed…”

Section: Multiple Sclerosismentioning

confidence: 99%

Polyspecific antibodies without persisting antigen in multiple sclerosis, neurolupus and Guillain-Barré syndrome: immune network connectivity in chronic diseases

Reiber¹

2017

Arq. Neuro-Psiquiatr.

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The polyspecific antibody synthesis in multiple sclerosis (MS) gained diagnostic relevance with the frequent combination of measles-, rubella-and varicella zoster antibodies (MRZ-antibody reaction) but their pathophysiological role remains unknown. This review connects the data for intrathecal polyspecific antibody synthesis in MS and neurolupus with observations in the blood of patients with Guillain-Barré syndrome (GBS). Simultaneously increased antibody and autoantibody titers in GBS blood samples indicate that the polyspecific antibodies are based on a general property of an immune network, supported by the deterministic day-to-day concentration variation of antibodies in normal blood. Strongly correlated measles-and rubella-antibody variations point to a particular connectivity between the MRZ antibodies. The immune network, which provides serological memory in the absence of an antigen, implements the continuous change of the MRZ pattern in blood, not followed by the earlier immigrated B cells without corresponding connectivity in the brain. This may explain the different antibody patterns in cerebrospinal fluid, aqueous humor and blood of the individual MS patient. A complexity approach must implement a different view on causation in chronic diseases and causal therapies.Keywords: cerebrospinal fluid; autoimmune diseases; antibodies; M,R,Z-antibody reaction; multiple sclerosis; Guillain-Barré syndrome, neurolupus. RESUMOA síntese de anticorpos poliespecíficos em esclerose múltipla (EM) ganhou relevância diagnóstica com a combinação frequente de anticorpos contra sarampo, rubéola e varicela-zoster (reação de anticorpos MRZ), mas seu papel fisiopatológico permanece desconhecido. Esta revisão relaciona os dados da síntese intratecal de anticorpos poliespecíficos em EM e Neurolupus com observações no sangue de pacientes com síndrome de Guillain Barré (SGB). Simultaneamente, os títulos aumentados de anticorpos e autoanticorpos em amostras de sangue de SGB indicam que os anticorpos poliespecíficos se baseiam numa propriedade geral de uma rede imunitária, suportada pela variação determinística da concentração diária de anticorpos no sangue normal. As variações fortemente correlacionadas de anticorpos contra sarampo e rubéola apontam para uma conectividade particular entre os anticorpos MRZ. A rede imunitária, que fornece memória sorológica na ausência de um antígeno, implementa a mudança contínua do padrão MRZ no sangue, não seguida pelas células B que imigraram anteriormente sem conectividade no cérebro. Isto pode explicar os diferentes padrões de anticorpos no LCR, humor aquoso e sangue do paciente individual de EM. Uma abordagem complexa deve implementar uma visão diferente sobre a causalidade em doenças crônicas e terapias causais.

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The intrathecal synthesis of virus-specific oligoclonal IgG in multiple sclerosis

Cited by 109 publications

References 23 publications

CNS viral infection diverts homing of antibody‐secreting cells from lymphoid organs to the CNS

CNS viral infection diverts homing of antibody‐secreting cells from lymphoid organs to the CNS

B cells in multiple sclerosis

Polyspecific antibodies without persisting antigen in multiple sclerosis, neurolupus and Guillain-Barré syndrome: immune network connectivity in chronic diseases

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