Biochemical findings in multiple sclerosis

Bollengier, F.; Delmotte, P.; Löwenthal, A.

doi:10.1007/bf00329158

Cited by 33 publications

(3 citation statements)

References 9 publications

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“…Studies in animal models, though, suggest a more complex function for B cells than antibody production, including antigen-driven B-cell effector functions, stimulation of T cells through antigen presentation, and contribution to tertiary lymphoid structure formation in the CNS (McLaughlin and Wucherpfennig, 2008). Intrathecal synthesis of antibodies, specifically oligoclonal IgG, is common in MS patients (Kabat et al, 1950; Bollengier et al, 1976). Though precise antigenic targets have yet to be identified, there is a direct correlation between IgG levels in CSF and MS disease progression (Villar et al, 2002).…”

Section: Insights Into Ms Pathogenesismentioning

confidence: 99%

The experimental autoimmune encephalomyelitis (EAE) model of MS

Robinson

Harp

Noronha

et al. 2014

Handbook of Clinical Neurology

362

158

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While no single model can exactly recapitulate all aspects of multiple sclerosis (MS), animal models are essential in understanding the induction and pathogenesis of the disease and to develop therapeutic strategies that limit disease progression and eventually lead to effective treatments for the human disease. Several different models of MS exist, but by far the best understood and most commonly used is the rodent model of experimental autoimmune encephalomyelitis (EAE). This model is typically induced by either active immunization with myelin-derived proteins or peptides in adjuvant or by passive transfer of activated myelin-specific CD4+ T lymphocytes. Mouse models are most frequently used because of the inbred genotype of laboratory mice, their rapid breeding capacity, the ease of genetic manipulation, and availability of transgenic and knockout mice to facilitate mechanistic studies. Although not all therapeutic strategies for MS have been developed in EAE, all of the current US Food and Drug Administration (FDA)-approved immunomodulatory drugs are effective to some degree in treating EAE, a strong indicator that EAE is an extremely useful model to study potential treatments for MS. Several therapies, such as glatiramer acetate (GA: Copaxone), and natalizumab (Tysabri), were tested first in the mouse model of EAE and then went on to clinical trials. Here we discuss the usefulness of the EAE model in understanding basic disease pathophysiology and developing treatments for MS as well as the potential drawbacks of this model.

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Section: Insights Into Ms Pathogenesismentioning

confidence: 99%

The experimental autoimmune encephalomyelitis (EAE) model of MS

Robinson

Harp

Noronha

et al. 2014

Handbook of Clinical Neurology

362

158

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“…Although specific antibodies, possibly of the kappa chain type, are most probably synthesized in the central nervous system of multiple sclerosis patients (1,2,3,16), it seems less likely that humoral antibodies of central nervous system specificity directly related to the disease are elaborated.…”

Section: The Aim Of Holding This International Symposium On Enzyme Lamentioning

confidence: 99%

Bound and Free Light Chains in Serum from Patients Affected with Various Neurological Diseases

Bollengier¹

1979

Clinical Chemistry and Laboratory Medicine

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Summary: Six immunological parameters, of which the most important are the quantitative distribution of the free light chains, and the kappa-lambda ratios of both bound and free light chains, were investigated in serum of patients affected with various neurological disorders and compared to controls.Subacute sclerosing panencephalitis and viral encephalitis, which are diseases characterized by hyperimmunisation against definite antigens, are accompanied by a considerable quantitative increase of free light chains; in subacute sclerosing panencephalitis serum there is an increase of both free kappa and lambda chains, whereas in viral encephalitis serum the increase of free light chains was restricted to lambda chains.There is a good correlation between the kappa-lambda ratio of, on the one hand, bound light chains and, on the other hand, free light chains for controls and subacute sclerosing panencephalitis; but in multiple sclerosis, amyotrophic lateral sclerosis and viral encephalitis, the ratios for bound light chains are totally different from ratios for free ligjit chains. A general kappa increase, which we earlier reported for bound light chains in 16 cases of multiple sclerosis, was not confirmed by the investigation of an additional 26 cases: kappa decrease was also noticed in a considerable number of cases. Gebundene und freie leichte Ketten im Serum von Patienten mit verschiedenen neurologischen ErkrankungenZusammenfassung: Sechs immunologische Größen -die wichtigsten sind die quantitative Verteilung der freien leichten Ketten und die Kappa-Lambda-Verhältnisse sowohl der freien als auch der gebundenen leichten Kettenwurden im Serum von Patienten mit verschiedenen neurologischen Störungen untersucht und mit denen von Kontrollpersonen verglichen.Subakute sklerosierende Panencephalitis und virale Encephalitis -Erkrankungen, die durch Hyperimmunisierung gegen bestimmte Antigene charakterisiert sind -sind begleitet von einem beträchtlichen quantitativen Anstieg freier leichter Ketten: im Serum von an subakuter sklerosierender Panencephalitis Erkrankten findet sich ein Anstieg freier Kappa-und Lambda-Ketten, während der Anstieg der freien leichten Ketten im Serum an viraler Encephalitis Erkrankter auf die Lambda-Ketten beschränkt war.Es besteht eine gute Korrelation zwischen dem Kappa-Lambda-Verhältnis sowohl der gebundenen leichten Ketten als auch der freien leichten Ketten bei den Kontrollpersonen und den an subakuter sklerosierender Panencephalitis Erkrankten; bei multipler Sklerose, amyotropher Lateralsklerose und viraler Encephalitis jedoch differieren die Verhältnisse für gebundene leichte Ketten völlig von denen für freie leichte Ketten. Ein genereller Anstieg der Kappa-Ketten, den wir früher fiir gebundene leichte Ketten in 16 Fällen von multipler Sklerose beschrieben haben, konnte bei Untersuchung zusätzlicher 26 Fälle nicht bestätigt werden: auch ein Abfall der Kappa-Ketten wurde in einer beträchtlichen Zahl der Fälle festgestellt.

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“…The cerebrospinal fluid (CSF) ofpatients with multiple sclerosis (MS) frequently contains restricted (oligoclonal) populations of Igs that are increased in concentration relative to other CSF Ig populations (1)(2)(3)(4)(5) and are thought to be produced by intrathecally localized B cells (6-9). Many attempts have been made to identify the specificity ofthese predominant CSF Ig populations in the hope offinding some clues to the nature of the antigen(s) involved in the pathogenesis of MS. Those studies have revealed predominant CSF Ig populations reactive with various viruses, most notably measles (reviewed in ref.…”

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confidence: 99%

Analysis of a predominant immunoglobulin population in the cerebrospinal fluid of a multiple sclerosis patient by means of an anti-idiotypic hybridoma antibody.

Gerhard¹,

Taylor²,

Wróblewska³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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We have produced hybridoma antibodies directed against immunoglobulins present in the cerebrospinal fluid ofa patient with multiple sclerosis (MS). One hybridoma antibody recognized an idiotypic determinant of an immunoglobulin population [an idiotype (Id)] which constituted approximately 1% of the immunoglobulin present in the cerebrospinal fluid. The Id focused in the pH range 8. 0-8.4. It was present at roughly 10-to 15-fold higher relative (compared to total immunoglobulin) concentration in cerebrospinal fluid than in serum of the homologous MS patient. The Id could not be detected in three cerebrospinal fluid samples and 28 serum samples of heterologous MS patients or in the serum of 43 optic neuritis patients. The Id persisted in the homologous MS patient at increased concentration over the entire (6 years) observation period. The Id could be shown to react with a Theiler murine encephalomyelitis virus strain WW which was isolated from mice after inoculation with periplaque white matter from brain in a histologically confirmed case of MS.The cerebrospinal fluid (CSF) ofpatients with multiple sclerosis (MS) frequently contains restricted (oligoclonal) populations of Igs that are increased in concentration relative to other CSF Ig populations (1)(2)(3)(4)(5) and are thought to be produced by intrathecally localized B cells (6-9). Many attempts have been made to identify the specificity ofthese predominant CSF Ig populations in the hope offinding some clues to the nature of the antigen(s) involved in the pathogenesis of MS. Those studies have revealed predominant CSF Ig populations reactive with various viruses, most notably measles (reviewed in ref. 10) and, in one case, reactive with smooth muscle antigens (11). These antibodies seem to account, however, only for a minor fraction of the oligoclonal . Thus, the specificity(ies) of most of the predominant Ig populations in the CSF of MS patients remains unknown.Recent studies by Baird et al. (15) and Nagelkerken et al. (16) have demonstrated the feasibility of producing anti-idiotypic antibodies by immunization of mice and guinea pigs, respectively, with CSF Ig of MS patients. Such anti-idiotypic antibodies may provide ideal reagents for investigation of the specificity ofpredominant CSF 1g. The present study describes the production of one such anti-idiotypic hybridoma antibody and its application in specificity analyses ofa predominant CSF Ig population. As controls, serum samples from 14 healthy Scandinavians were obtained, and a normal Ig pool was prepared from serum samples of 70 healthy North Americans. The pooled serum was precipitated with ammonium sulfate at 42% saturation. The precipitate was then redissolved in and dialyzed against 0.1 M K phosphate buffer at pH 7.4 and subsequently purified on DE-32 as described for CSF Ig. MATERIALSProduction of Murine Anti-CSF-Ig Hybridomas. A/J mice were immunized by four intraperitoneal inoculations with 100 ,ug of Ig (1:9 in complete Freund's adjuvant) partially purified from pooled (1974)(1975)(19...

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Biochemical findings in multiple sclerosis

Cited by 33 publications

References 9 publications

The experimental autoimmune encephalomyelitis (EAE) model of MS

The experimental autoimmune encephalomyelitis (EAE) model of MS

Bound and Free Light Chains in Serum from Patients Affected with Various Neurological Diseases

Analysis of a predominant immunoglobulin population in the cerebrospinal fluid of a multiple sclerosis patient by means of an anti-idiotypic hybridoma antibody.

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