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Intrathecal IgG synthesis in multiple sclerosis: Comparison between isoelectric focusing and quantitative estimation of cerebrospinal fluid IgG

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Summary

Isoelectric focusing of CSF and serum IgG followed by crossed immuno isoelectric focusing and direct immunofixation as well as quantitative assay of IgG and albumin were performed in 64 clinically definite multiple sclerosis patients. Intrathecal IgG synthesis was calculated according to the CSF IgG index and de novo CNS IgGsyn. Isoelectric focusing showed abnormal IgG fractions in CSF indicating increased intrathecal synthesis of oligoclonal IgG in 99% of patients. Only 62% and 70% of multiple sclerosis patients showed values of CSF IgG indices and de novo CNS IgGsyn higher than in controls. Increased intrathecal IgG synthesis was indicated more frequently by de novo CNS IgGsyn in patients with a normal CSF IgG index than by the CSF IgG index in patients with normal de novo CNS IgGsyn. All patients with blood CSF barrier damage had increased de novo CNS IgGsyn, but only 40% had an increased CSF IgG index. Isoelectric focusing seemed to be a more sensitive method to detect an increased intrathecal oligoclonal IgG synthesis than quantitative methods. Identification of abnormal IgG fractions can be performed easily and with more reproducible results by direct immunofixation than by crossed immuno isoelectric focusing. The formula for de novo CNS IgGsyn seemed more sensitive and less influenced by blood-CSF barrier damage than the CSF IgG index to detect increased intrathecal IgG synthesis in multiple sclerosis patients. No correlation was found between the CSF IgG pattern or amounts and age, duration, clinical course or therapy of the disease.

Zusammenfassung

Bei 64 klinisch bestimmten Fällen von multipler Sklerose wurde die isoelektrische Fokussierung von CSF und Serum-IgG, gefolgt von „crossed“ immuno-isoelektrischer Fokussierung und direkter Immunofixierung, sowohl bei der quantitativen Bestimmung als auch bei Albumin, durchgeführt. Die IgG-intrathekal-Synthese wurde entsprechend dem CSF-IgG-Index und de-novo-CNS-IgGsyn berechnet. Bei 99% der Patienten zeigte die isoelektrische Fokussierung abnorme Fraktionen im CSF an, ein Hinweis auf eine erhöhte intrathekale Synthese von oligoklonalem IgG. Nur bei 62–70% der Multiple-Sklerose-Fälle waren die Werte des CSF-IgG-Index und de-novo-CNS-IgGsyn höher als bei Vergleichskontrollen. Eine erhöhte intrathekale Synthese wurde häufiger von de-novo-CNS-IgGsyn bei Patienten mit normalem CSF-IgG-Index als von CSF-IgG-Index bei Patienten mit normalem de-novo-CNS-IgGsyn angezeigt. Bei allen Patienten mit Störung der Blut-CSF-Schranke war de-novo-CNS-IgGsyn erhöht, dagegen wurde bei nur 40% eine Erhöhung des CSF-IgG-Index festgestellt. Im Vergleich zu den quantitativen Verfahren scheint die isoelektrische Fokussierung die genauere Methode zur Feststellung einer erhöhten Intrathekal-oligoklonal-IgG-Synthese zu sein. Abnorme IgG-Fraktionen werden eher durch direkte Immunofixierung einfacher und mit wenig voneinander abweichenden Resultaten festgestellt als durch immunoisoelektrische Fokussierung. Die Formel für die de-novo-CNS-IgGsyn scheint sensibler und weniger durch Störungen der Blut-CSF-Schranke beeinflußbar zu sein als der CSF-IgG-Index bei der Bestimmung erhöhter Intrathekal-IgG-Synthese bei Fällen von multipler Sklerose. Es wurde kein Zusammenhang zwischen der CSF-IgG-Zusammensetzung und den Werten zum Alter, der Krankheitsdauer, dem klinischen Verlauf und der Behandlungstherapie des Kranken gefunden.

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Authors and Affiliations

  1. Department of Neurology, University of Bari, 70124, Bari, Italy

    P. Livrea, M. Trojano, I. L. Simone, G. B. Zimatore, G. Lamontanara & R. Leante

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  1. P. Livrea
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  2. M. Trojano
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  3. I. L. Simone
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  4. G. B. Zimatore
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  5. G. Lamontanara
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Livrea, P., Trojano, M., Simone, I.L. et al. Intrathecal IgG synthesis in multiple sclerosis: Comparison between isoelectric focusing and quantitative estimation of cerebrospinal fluid IgG. J Neurol 224, 159–169 (1981). https://doi.org/10.1007/BF00313278

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