Comparison of seven formulae and isoelectrofocusing for deter- mination of intrathecally produced IgG in neurological diseases

SUMMARY. Seven different formulae and agarose isoelectrofocusing (AIF) using immunolabelIing for IgG were compared for their ability to discriminate between intrathecally produced IgG and transudated IgG in cerebrospinal fluid. All reference limits were set to a specificity of 97 ' 5070 (reference group, n = 211). The probability of a positive test (p+) was evaluated for 112 patients with multiple sclerosis (MS), 42 with meningitis, 114 with noninflammatory diseases affecting the central nervous system (CNS), 23 with Guillairi-Barre syndrome, and 56 with various diseases not affecting the CNS. Agarose isoelectrofocusing had the best diagnostic sensitivity (93%) for MS, combined with a low p+ (0-19070) for other diseases. Among the formulae, the IgG extended index and Reiber's hyperbolic formula were equivalent, giving high (75-79%) diagnostic sensitivity for MS combined with low p; (4-22%) for other diseases. All other formulae, although sensitive for MS, had a higher rate of false positive results. Additional key phrases: multiple sclerosis; meningitis; Guillain-Barre syndrome; reference values Intrathecal production of immunoglobulin G (IgG) is commonly associated with neuro-inflammatory diseases such as multiple sclerosis (MS), and detection of such synthesis has long been an established diagnostic tool. 1 In cerebrospinal fluid (CSF) IgG derives not only from intrathecal synthesis (lgG;), but a large and varied amount derives from serum through transudation (lgG1). 2 Several formulae have appeared in order to discriminate IgG j from the total amount of IgG in CSF.2,3 Comparisons between such formulae have revealed that they have considerably different capabilities to detect IgG/-s Only one of these comparisons ' covered the most recent formu-lae,6,7 but that study was not done according to the recommendations of the International Federation of Clinical Chemistry (IFCC),9 and it also included use of agarose iso-electric focusing (AIF) followed by silve