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

The 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.

Based on a mathematical model of ITS, we constructed a population of healthy controls and applied a tunable ITS.

We 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.

Studies evaluating changes in ITS level should be adjusted to Q _Alb. Low amounts of ITS could be largely underestimated.