The Intrathecal Humoral Immune Response: Laboratory Analysis and Clinical Relevance

Abstract

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 intrathecally synthesized, but the major fraction is blood-derived. The CSF/serum albumin quotient (Q_Alb) is the best marker of the blood-CSF barrier function. The corresponding immunoglobulin quotients (Q_IGG, Q_IGA, Q_IGM ) are not linearly related to Q_Alb and their correlations are defined by an hyperbolic equation. This equation is used to discriminate between a blood-derived and a locally produced fraction of immunoglobulins in case of an intrathecal humoral immune response. The detection of CSF-specific oligoclonal IgG is more sensitive than the quantitative comparison between Q_IGG and Q_Alb. A further step is the determination of antibody indices and the detection of specific oligoclonal antibodies by antigen-driven immunoblots. CSF analysis remains a cornerstone for the diagnosis of various neurological disorders, including multiple sclerosis and infectious diseases of the central nervous system.