FORMULAS FOR THE QUANTITATION OF INTRATHECAL IGG PRODUCTION - THEIR VALIDITY IN THE PRESENCE OF BLOOD-BRAIN-BARRIER DAMAGE AND THEIR UTILITY IN MULTIPLE-SCLEROSIS

There are several formulas for the quantitative determination of intra thecal IgG production:. Reiber and Felgenhauer's formula (IgG(loc)), t he Extended IgG index, Tourtellotte's formula (TOURT), Schuller and Sa gar's formula (SCHULL), the IgG index, the Log IgG index, and Blennow and co-workers' formula (IGGPROD). To evaluate the utility of these fo rmulas in the presence of blood-brain barrier (BBB) damage, we present the results from a study of serum and cerebrospinal fluid (CSF) sampl es from 125 healthy individuals, 18-88 years of age; 1072 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, 683 without BBB damage (CSF/S: albumin ratio < 9.8) and 389 with BBB damage (CSF/S albumin ratio 9.8-30); and 106 patients with definite multiple sclero sis (MS). The relation between the CSF/S albumin ratio and the CSF/S I gG ratio was remarkably linear in both healthy individuals (r = 0.95; P < 0.0001) and patients without oligoclonal bands in the CSF (r = 0.9 5; P < 0.0001). Therefore, IgG(loc) and the Extended IgG index, two fo rmulas based on a nonlinear relation between the CSF/S albumin ratio a nd the CSF/S IgG ratio, yielded biased results (lower values) in the p resence of BBB damage. TOURT and SCHULL also yielded biased (higher) v alues in the presence of BBB damage, probably because of incorrect con stants in these formulas. There were no significant correlations betwe en the CSF/S albumin ratio (i.e. the BBB function) and the IgG index o r the Log IgG index, two dimensionless quotients for the detection of intrathecal IgG production, or between the CSF/S albumin ratio and IGG PROD, an empirical formula for the determination of intrathecal IgG pr oduction in mg/l. These results show that the IgG index, the Log IgG i ndex and IGGPROD all give valid quantitative determinations of intrath ecal IgG production even in the presence of BBB damage. The percentage of MS patients with a formula value higher than the mean + 2 SD of th e control value was identical for the IgG index, the Log IgG index and IGGPROD (92%), and similar to the number of MS patients exhibiting OC Bs in their CSF (96%). These results suggest that the quantitative det ermination of intrathecal IgG production is almost as sensitive as the qualitative detection of OCBs for demonstration of intrathecal IgG pr oduction.