The intrathecal humoral immune response: Laboratory analysis and clinical relevance

In normal conditions, albumin and immunoglobulin (Ig)G in the cerebrospinal fluid (CSF) originate from the blood, and there is no antibody production within the central nervous system. Up to 20% of CSF proteins are intratheca lly synthesized, but the major fraction is blood-derived. The CSF/serum alb umin quotient (Q(Alb)) is the best marker of the blood-CSF barrier function . The corresponding immunoglobulin quotients (Q(IGG), Q(IGA), Q(IGM)) are n ot linearly related to Q(Alb) and their correlations are defined by an hype rbolic equation. This equation is used to discriminate between a blood-deri ved and a locally produced fraction of immunoglobulins in case of an intrat hecal humoral immune response. The detection of CSF-specific oligoclonal Ig G is more sensitive than the quantitative comparison between Q(IGG) and Q(A lb). A further step is the determination of antibody indices and the detect ion of specific oligoclonal antibodies by antigen-driven immunoblots. CSF a nalysis remains a cornerstone for the diagnosis of various neurological dis orders, including multiple sclerosis and infectious diseases of the central nervous system.