Quantitation of intrathecal measles virus IgG antibody synthesis rate: Subacute sclerosing panencephalitis and multiple sclerosis

Conrad, Andrew; Chiang, Edna Y.; Andeen, L.E.; Avolio, Carlo; Walker, Sharyn M.; Baumhefner, Robert W.; Mirzayan, R.; Tourtellotte, W. W.

doi:10.1016/0165-5728(94)90236-4

Cited by 47 publications

(24 citation statements)

References 23 publications

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“…Second, CSF oligoclonal bands are present not only in MS, but also in chronic bacterial, fungal, parasite and viral CNS infections in which this intrathecal oligoclonal antibody response is directed against the causative agent (Contini et al, 1998;Fainardi et al, 2001;Scarisbrick and Rodriguez, 2003;Gilden, 2005). Nevertheless, in CNS infections only 20-30% of intrathecally produced antibodies are directed against the causative agent, whereas the remaining 70% represent a polyspecific intrathecal immune response directed to many different pathogens not related to the cause of the disease (Conrad et al, 1994). Third, treatment with an antiviral agent, such as interferon-beta, is beneficial in MS patients (Javed and Reder, 2006).…”

Section: Evidence For An Infectious Pathogenesis In Msmentioning

confidence: 95%

Under the Microscope: Focus on Chlamydia pneumoniae Infection and Multiple Sclerosis

Fainardi¹,

Castellazzi²,

Seraceni³

et al. 2008

CNR

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Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the Central Nervous System (CNS) of supposed autoimmune origin whose etiology still remains unknown. Epidemiological studies suggest that MS pathogenesis could be related to an infection superimposed on a predisposing genetic background. However, at present, no direct evidence for an infectious implication in MS autoimmunity exists. Recently, the potential role of Chlamydia pneumoniae as a causative agent of MS has received increasing attention. After the initial high rates reported for molecular and culture demonstration of C. pneumoniae in cerebrospinal fluid (CSF) of MS patients, the association between C. pneumoniae and MS was intensively investigated with controversial results. Seroepidemiological reports did not show any strong association between C. pneumoniae infection and the risk of MS. Isolation techniques failed to detect C. pneumoniae in CSF and brain tissue of MS patients. Polymerase chain reaction (PCR) evidence of C. pneumoniae in CSF and intrathecal synthesis of anti-C. pneumoniae IgG have been undetectable in MS patients or, if present, were not selectively associated with MS, but were shared by several inflammatory neurological conditions. Nevertheless, in a subgroup of MS patients, an association between PCR positivity for C. pneumoniae in CSF and disease activity was found. Intrathecal production of anti-C. pneumoniae high-affinity IgG predominated in MS progressive forms and metabolically active C. pneumoniae was identified in CSF. C. pneumoniae was recognized in CSF and brain tissue at immunohistochemical, molecular and ultrastructural levels. C. pneumoniae was also able to induce the animal model of MS. This growing body of data does not support a central role for C. pneumoniae as a candidate in MS pathogenesis, but suggests that, in a subset of MS patients, C. pneumoniae could induce a chronic persistent brain infection acting as a cofactor in the development of the disease. Thus, the actual involvement of C. pneumoniae in MS still remains to be elucidated.

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Section: Evidence For An Infectious Pathogenesis In Msmentioning

confidence: 95%

Under the Microscope: Focus on Chlamydia pneumoniae Infection and Multiple Sclerosis

Fainardi¹,

Castellazzi²,

Seraceni³

et al. 2008

CNR

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“…In contrast, the amount of intrathecal antibodies synthesized in the presence of a persistent virus is 10-20% of total IgG (HSV in HSV encephalitis, measles in SSPE), i.e., their intrathecally synthesized amount of antibodies is 20-60 fold higher than the polyspecific antibodies in MS (Conrad et al, 1994;Jacobi et al, 2007). This is also reported for the rubella-caused Fuchs' heterochromic cyclitis (FHC) in the eye: The mean rubella antibody fraction in AH is 2.6% of total intraocular IgG, which is 40 fold higher than the mean amount of rubella antibodies as part of the polyspecific immune response in AH of MS patients (Quentin and Reiber, 2004).…”

Section: Antibody Quantitiesmentioning

confidence: 85%

Antibody patterns vary arbitrarily between cerebrospinal fluid and aqueous humor of the individual multiple sclerosis patient: Specificity-independent pathological B cell function

Reiber

Kruse-Sauter

Quentin

2015

Journal of Neuroimmunology

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“…For example, the calculation of an F s value for measles at 2% means that 2% of the total intrathecal IgG response is directed against measles. Neuro-infections are expected to be associated with very high F s against the virus: F s are 8.8% (3.5–12.5%) for HSV in HSV encephalitis (HSVE), 18.8% (11.8–27.5%) for measles in subacute sclerosis panencephalitis (SSPE) (49, 50) and 45% (13–73%) for VZV encephalitis (51). Unfortunately F s values for relevant infectious agents are not available in other infectious settings such as neuro-syphilis and neuro-borreliosis.…”

Section: Non-specific Synthesis Is Also a Feature Of Non-ms Cns Disormentioning

confidence: 99%

Does Disease-Irrelevant Intrathecal Synthesis in Multiple Sclerosis Make Sense in the Light of Tertiary Lymphoid Organs?

Bonnan

2014

Front. Neurol.

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Although partly disease-irrelevant, intrathecal immunoglobulins (Ig) synthesis is a typical feature of multiple sclerosis (MS) and is driven by the tertiary lymphoid organs (TLO). A long-known hallmark of this non-specific intrathecal synthesis is the MRZ pattern, an intrathecal synthesis of Ig against measles, rubella, and zoster viruses. This non-specific intrathecal synthesis could also be directed against a wide range of pathogens. However, it is highly problematic since brain TLO should not be able to drive the clonal expansion of lymphocytes against alien antigens that are thought to be absent in MS brain. We propose to explain the paradox of non-specific intrathecal synthesis by discussing the natural properties of TLO. In fact, besides local antigen-driven clonal expansion, circulating plasmablasts and plasma cells (PC) are non-specifically recruited from blood and gain access to survival niches in the inflammatory CNS. This mechanism, which has been described in other inflammatory disorders, takes place in the TLO. As a consequence, PCs recruited in brain mirror the individual’s history of immunization and intrathecal synthesis of IgG in MS may target a broad range of common infectious agents, a hypothesis in line with epidemiological data. Moreover, the immunization schedule and its timing may interfere with PC recruitment. If this hypothesis is correct, the reaction against EBV appears paradoxical: although early infection of MS patients is systematic, intrathecal synthesis is far lower than expected, suggesting a crucial interaction between MS onset and timing of EBV infection. A growing body of evidence suggests that the non-specific intrathecal synthesis observed in MS is also common in many chronic CNS inflammatory disorders. Assuming that cortical TLO in MS are associated with typical sub-pial lesions, we have coined the concept of “TLO-pathy” to describe these lesions and take examples of them from non-MS disorders. Lastly, we propose that intrathecal synthesis could be considered a strong hallmark of CNS TLO and might be used to monitor future TLO-targeted therapies.

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Quantitation of intrathecal measles virus IgG antibody synthesis rate: Subacute sclerosing panencephalitis and multiple sclerosis

Cited by 47 publications

References 23 publications

Under the Microscope: Focus on Chlamydia pneumoniae Infection and Multiple Sclerosis

Under the Microscope: Focus on Chlamydia pneumoniae Infection and Multiple Sclerosis

Antibody patterns vary arbitrarily between cerebrospinal fluid and aqueous humor of the individual multiple sclerosis patient: Specificity-independent pathological B cell function

Does Disease-Irrelevant Intrathecal Synthesis in Multiple Sclerosis Make Sense in the Light of Tertiary Lymphoid Organs?

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