The intrathecal, polyspecific antiviral immune response in neurosarcoidosis, acute disseminated encephalomyelitis and autoimmune encephalitis compared to multiple sclerosis in a tertiary hospital cohort

Hottenrott, Tilman; Dersch, Rick; Berger, Benjamin; Rauer, Sebastian; Huzly, Daniela; Stich, Oliver

doi:10.1186/s12987-015-0024-8

Cited by 33 publications

(36 citation statements)

References 25 publications

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“…Moreover, it would be relevant to investigate both the IgG1 allotype restriction and the intrathecal polyspecific anti‐viral reaction in MS patients with other genetic backgrounds, such as Asian/Mongoloid populations, in which there has been a chromosomal crossover, leading to another combination of IgG1 allotypes in a proportion of the individuals. Here, we found similar levels of intrathecal virus‐specific antibodies as previous studies 4, 24, 25. Thus, it is unlikely that selection bias has influenced our results.…”

Section: Discussionsupporting

confidence: 90%

G1m1 predominance of intrathecal virus‐specific antibodies in multiple sclerosis

Tomescu-Baciu

Vartdal

Holmøy

et al. 2018

Ann Clin Transl Neurol

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We have previously shown that plasmablasts of the G1m1 allotype of IgG1 are selectively enriched in the cerebrospinal fluid of G1m1/G1m3 heterozygous patients with multiple sclerosis, whereas both allotypes are equally used in neuroborreliosis. Here, we demonstrate a strong preference for the G1m1 allotype in the intrathecal humoral immune responses against measles, rubella, and varicella zoster virus in G1m1/G1m3 heterozygous multiple sclerosis patients. Conversely, intrathecally synthesized varicella zoster virus‐specific IgG1 in varicella zoster virus meningoencephalitis comprised both allotypes. This implies that G1m1 B cells are selected to the central nervous system of multiple sclerosis patients regardless of specificity and suggests that an antigen‐independent mechanism could drive the intrathecal humoral immune response.

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Section: Discussionsupporting

confidence: 90%

G1m1 predominance of intrathecal virus‐specific antibodies in multiple sclerosis

Tomescu-Baciu

Vartdal

Holmøy

et al. 2018

Ann Clin Transl Neurol

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“…However, a relapsing disease course suggestive for MS was not reported by the patient. Additionally, the cMRI Swanton criteria for dissemination in time and space were not fulfilled and the MRZ reaction, a polyspecific, intrathecal humoral immune response against neurotropic agents (measles, rubella, and varicella zoster virus), which is possibly the most specific available CSF marker for MS (26), was also negative. Therefore, we were not able to diagnose MS or an early stage of this disease although previous studies showed an association between BD and MS (27, 28).…”

Section: Discussionmentioning

confidence: 99%

Alterations in Cerebrospinal Fluid in Patients with Bipolar Syndromes

et al. 2016

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Bipolar disorder (BD) is a severe and lifelong condition. Primary endogenic polygenetic forms are common. Secondary organic forms have received increasing interest recently due to the detection of immunological encephalopathies that mimic various psychiatric syndromes, including BD. However, only limited data about routine findings of cerebrospinal fluid (CSF) analyses in BD are available. Therefore, we investigated the frequency of alterations in the CSF in patients with BD and the association with autoantibodies, cerebral magnetic resonance imaging, and electroencephalography findings. CSF samples of patients with BD collected from January 1998 until December 2015 were analyzed retrospectively. Patients with preexisting causes for alterations in the CSF (e.g., patients with obvious past or current neurological disorders) were excluded. In total, 63 patients with BD fulfilled the inclusion criteria for the study. In 1.6% of the patients with BD, an increased white blood cell count was found in the CSF. Increased albumin quotients were found in 12.9% of the patients, oligoclonal bands (OCBs) in 1.6%, and increased immunoglobulin (Ig) G indices in 3.2% (OCBs were not measured in case of increased IgG indices). No significant differences in CSF findings were found between patients with manic and depressive episodes. The main findings of this open uncontrolled study are that alterations in the CSF may be found in a small, but potentially relevant, subgroup of patients with BD. These findings are discussed in light of the new concepts of mild encephalitis and immunological encephalopathy. The detection of patients with possibly secondary organic bipolar syndromes could open up new causal treatment options with immunomodulatory medication.

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“…Frequency of Guillain-Barré (GBS) patients (total n = 56, Table 3) with the number of simultaneously-increased antibody titers in blood (total n = 22 antibody species analyzed) 8 . The fit with a Gaussian function shows a mean connectivity of five antibody species out of IgG 19 and IgM 3 class antibodies against 19 infectious microbes.…”

Section: Normal Antibody Dynamics In Bloodmentioning

confidence: 98%

“…There is a discontinuity between an infection or vaccination and the recognition of an autoimmune disease or multisymptom illnesses of a few weeks to two months 3,4,5,6 after the initiating event. In MS, as well, there is no development such as starting with an acute demyelinating meningoencephalitis and slowly becoming an MS 19,25 . The youngest patient, investigated at age of five years 25 , already had the complete set of immune reactions, like a complete MRZ antibody reaction 25 .…”

Section: Causation In Chronic Diseasesmentioning

confidence: 99%

“…The combined analysis, the so-called MRZ antibody reaction 9 , is the most sensitive measure for the detection of a polyspecific antibody synthesis, and this gained diagnostic relevance for detection of a chronic inflammatory process in the brain 10,16,17,18,19 . The MRZ antibody reaction is typical in chronic diseases, but missing in acute inflammatory diseases.…”

mentioning

confidence: 99%

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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, polyspecific antiviral immune response in neurosarcoidosis, acute disseminated encephalomyelitis and autoimmune encephalitis compared to multiple sclerosis in a tertiary hospital cohort

Cited by 33 publications

References 25 publications

G1m1 predominance of intrathecal virus‐specific antibodies in multiple sclerosis

G1m1 predominance of intrathecal virus‐specific antibodies in multiple sclerosis

Alterations in Cerebrospinal Fluid in Patients with Bipolar Syndromes

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

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