Diagnostic methods for demonstration of intrathecal synthesis of immunoglobulines within the central nervous system

Abstract: This thesis is based upon studies of quantitative and qualitative determinations of immunoglobulins A, G, and M (lgA, IgG, and IgM) in cerebrospinal fluid (CSF) and in serum. Inflammatory diseases, such as multiple sclerosis and infections (e.g. meningitis) affecting the central nervous system are characterized by intrathecal synthesis of immunoglobulins, and therefore determinations of them in CSF are important diagnostic tools.A non-linear relationship between the CSF/serum ratios of IgG, IgA, IgM, and albumin was found in patients with damaged blood-CSF barrier, but in whom no intrathecal synthesis orimmunoglobulins was expected. On the basis of this non-linear relationship a new kind of formula, the extended indices (lgA-EI, IgG-EI, and IgM-EI), was developed to giveimproved estimates of intrathecal synthesis.These formulae were evaluated together with other proposed formulae and with agarose isoelectrofocusing, to determine their diagnostic sensitivities in different neurological diseases. The main advantage with the extended indices, compared to other formulae, was a lower rate offalse positive tests, without affecting the diagnostic sensitivities for intrathecal immunoglobulin synthesis.A method based on ultracentrifugation is presented, where the distribution of monomeric and dimeric IgA in CSF and serum can be determined quantitatively. Both total and Ilerpes simplex virus specific lgA antibodies were estimated with respect to the physical form of lgA.For determination of CSF-IgM the sampling should be performed with an atraumatic Sprotte needle to minimise pre-analytical errors owing to contamination with serum or interstitial fluid.