Quantitation of intrathecal immunoglobulin synthesis – a new empirical formula

Auer, Michael; Hegen, Harald; Zeileis, Achim; Deisenhammer, Florian

doi:10.1111/ene.12924

Cited by 33 publications

(28 citation statements)

References 30 publications

(56 reference statements)

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“…This fact is often not considered by CSF labs. For intrathecal synthesis of immunoglobulins it is well-known that the widespread Reiber-formula overestimates particularly intrathecal IgM and IgA synthesis rates (4, 6).…”

Section: Part I: the Clinical Laboratorymentioning

confidence: 99%

The Cerebrospinal Fluid in Multiple Sclerosis

Deisenhammer

Zetterberg

Fitzner³

et al. 2019

Front. Immunol.

127

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Investigation of cerebrospinal fluid (CSF) in the diagnostic work-up in suspected multiple sclerosis (MS) patients has regained attention in the latest version of the diagnostic criteria due to its good diagnostic accuracy and increasing issues with misdiagnosis of MS based on over interpretation of neuroimaging results. The hallmark of MS-specific changes in CSF is the detection of oligoclonal bands (OCB) which occur in the vast majority of MS patients. Lack of OCB has a very high negative predictive value indicating a red flag during the diagnostic work-up, and alternative diagnoses should be considered in such patients. Additional molecules of CSF can help to support the diagnosis of MS, improve the differential diagnosis of MS subtypes and predict the course of the disease, thus selecting the optimal therapy for each patient.

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Section: Part I: the Clinical Laboratorymentioning

confidence: 99%

The Cerebrospinal Fluid in Multiple Sclerosis

Deisenhammer

Zetterberg

Fitzner³

et al. 2019

Front. Immunol.

127

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“…While methods for quantifying ITS (IgG Loc ) have been largely debated and several formulas have been proposed,16, 17 the formula derived from the Reibergram remains the best approach although it provides only an approximation 12. However, as we demonstrate above, whatever the choice of Q Lim cut‐off, results concerning “silent ITS” remain mostly unchanged: that is ROC curves calculated (not shown) with the procedure described by Auer et al 17. are very close to those obtained with Reiber's formula.…”

Section: Discussionmentioning

confidence: 99%

Estimation of intrathecal IgG synthesis: simulation of the risk of underestimation

Bonnan

Gianoli-Guillerme

Courtade

et al. 2018

Ann Clin Transl Neurol

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ObjectiveThe low level of passively diffused IgG through the blood–brain barrier is sufficient to blur the estimation of intrathecal IgG synthesis (ITS). Therefore, this estimation requires a mathematical calculation derived from empirical laws, but the range of normal values in healthy controls is wide enough to prevent a precise calculation. This study investigated the precision of various methods of ITS estimations and their application to two clinical situations: plasma exchange and immune suppression targeting ITS.MethodsBased on a mathematical model of ITS, we constructed a population of healthy controls and applied a tunable ITS.ResultsWe demonstrate the following results: underestimation of ITS is common at individual level but true ITS is well fitted by cohorts; Q IgG increases after plasma exchange; IgG Loc calculation based on Qlim falsely increases when Q Alb decreases; the sample size required to demonstrate a decrease in ITS increases exponentially with larger Q Alb.InterpretationStudies evaluating changes in ITS level should be adjusted to Q Alb. Low amounts of ITS could be largely underestimated.

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“…Při srovnání výpočtových metod intratékální syntézy IgG s IEF v agaróze a imunofixací nebyly zjištěny žádné falešně pozitivní výsledky výpočtu podle Reibera [15], Auera et al [16] ani Öhmana et al [17]. Jeden falešně pozitivní výsledek byl pozorován v případě IgG indexu (při použití konvenčního kritéria > 0,7).…”

Section: Srovnání S Výpočty Intratékální Syntézy Igg a Flcunclassified

Oligoclonal IgG and free light chains – comparison between agarose and polyacrylamide isoelectric focusing

Zeman¹,

Kušnierová²,

Hradílek³

et al. 2019

Cask Slov Neurol N

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Oligoclonal IgG and free light chains-comparison between agarose and polyacrylamide isoelectric focusing Souhrn Cíl: Porovnání izoelektrické fokusace v agarosovém a polyakrylamidovém gelu pro detekci oligoklonálních pásů imunoglobulinu G (o-IgG) a oligoklonálních volných lehkých řetězců (oligoclonal free light chains; o-fLC). Soubor a metody: Detekce oligoklonálních pásů byla provedena v sérii 106 (o-IgG), resp. 48 (o-fLC) konsekutivních párových vzorků likvorů a sér. Pro srovnání obou metod a shody mezi hodnotícími byla použita statistika kappa. Výsledky: Při rozdělení nálezů na negativní a pozitivní byly rozdílně hodnoceny jen tři vzorky (2,8 %) pro o-IgG, tři vzorky (6,2 %) pro o-fLC kappa a jediný vzorek (2,1 %) pro o-fLC lambda. V těchto diskrepantních případech byl pozorován rozdíl nejvýše tří pásů. Shoda mezi hodnotícími pro o-fLC byla velmi dobrá (κ = 0,906-1,000). Závěry: Přestože polyakrylamidový gel může být teoreticky výhodnější vzhledem k menší velikosti pórů a lepšímu rozlišení, naše výsledky byly jak pro o-IgG, tak pro o-fLC velmi podobné jako při separaci v agarózovém gelu. Obě metody hodnotíme jako dobře použitelné a rozdíly mezi nimi byly omezeny na hraničně pozitivní případy.

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Quantitation of intrathecal immunoglobulin synthesis – a new empirical formula

Abstract: A new approximation formula was developed for determination of intrathecal Ig synthesis which produces fewer false positive results without reducing diagnostic sensitivity.

Cited by 33 publications

References 30 publications

The Cerebrospinal Fluid in Multiple Sclerosis

The Cerebrospinal Fluid in Multiple Sclerosis

Estimation of intrathecal IgG synthesis: simulation of the risk of underestimation

Oligoclonal IgG and free light chains – comparison between agarose and polyacrylamide isoelectric focusing

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