The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis

Abstract

We report an extended set of neuroimmunological data detected in cerebrospinal fluid (CSF) from n = 267 patients with definite multiple sclerosis (MS). Known frequencies of oligoclonal IgG (98%), frequencies of intrathecal fractions of IgG, IgA and IgM (72%, 9% and 20%, respectively) were confirmed and quantitated as intrathecal fractions, IgIF or CSF concentrations, IgLOC. Eighty-nine per cent of the patients had a combined 'MRZ-reaction', i.e. intrathecal antibody synthesis (Antibody Index, AI > 1.4) against measles, rubella and/or varicella zoster virus. Frequencies of single antibodies decreased from measles (78%) to rubella (60%), VZV (55%) and HSV (28%). This MRZ-reaction, indicating a chronic autoimmune type disease already at time of first clinical symptoms, is less sensitive but more specific than detection of oligoclonal IgG. With increasing intrathecal IgG synthesis the number of different locally synthesized antibody species were increased as well as the amount per species (increased mean AI values). The concentration of MRZ antibodies in CSF represents together about 2% of intrathecally synthesized total IgG. But, as a very particular result the ratio of intrathecally synthesized specific antibody/intrathecally synthesized JgG was 5-fold higher (0.24-0.85%) compared to the corresponding ratio in blood (0.06-0.17%) of MS patients. This difference between brain ratio and blood ratio is discussed to be indicative for the anti-MRZ antibody forming B-lymphocyte subset in blood migrating into brain at earlier time of pathophysiological start of disease. These results give a concise explanation of neuroimmunological aspects in MS, not understood so far.