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

Abstract

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.

Noninvasive tools based on immune biomarkers for the diagnosis of central nervous system graft-vs-host disease: Two case reports and a review of the literature

“…IgG-Syn is used to diagnose neurological diseases, such as multiple sclerosis. Bonnan et al [ 22 ] reported that IgG-Syn is a robust marker of persistent intrathecal inflammation[ 22 ], and its complete normalization should be one of the goals of future therapeutic strategies. Zhang et al [ 23 ] found that BBB permeability, CSF IgG-Syn and MOG.Ab were related to the occurrence of CNS demyelination[ 23 ].…”

Acute Graft-Versus-Host Disease, Infections, Vascular Events and Drug Toxicities Affecting the Central Nervous System

“…Due to the rarity of CNS-GVHD and the difficulty to distinguish the disease from other mediators of CNS toxicity, biomarkers to identify CNS-GVHD would be highly desirable. IgG index in the CSF is an indicator of neurological disorders like multiple sclerosis, intrathecal inflammation ( 35 , 36 ). Another study indicated that Blood Brain Barrier (BBB) impermeability, IgG –Synthesis index are early indicators of CNS demyelination ( 37 ).…”