Intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis is part of a polyspecific immune response

Chronic intrathecal immunoglobulin (Ig) production is a hallmark of multipl e sclerosis characterized by the presence of oligoclonal IgGs and, in addit ion, polyspecific recognition of different pathogens such as measles, rubel la and herpes tester virus. While the antigen specificity of the oligoclona l IgGs in multiple sclerosis is largely unknown, the oligoclonal IgGs arisi ng during CNS infectious diseases are reactive against the specific pathoge n. Recently, a link between Chlamydia pneumoniae and multiple sclerosis has been claimed. To test the possible role of C. pneumoniae in multiple scler osis, we analysed (i) whether there is intrathecal IgG production against C . pneumoniae in multiple sclerosis and (ii) if the oligoclonal IgGs in the CSF of multiple sclerosis patients recognize C. pneumoniae. By studying pai red serum-CSF samples from 120 subjects (definite multiple sclerosis, 46; p robable multiple sclerosis, 12; other inflammatory neurological diseases, 3 5; other neurological diseases, 27) by enzyme-linked immunosorbent assay, w e found that 24% of all patients with definite multiple sclerosis, but only 5% of patients with other inflammatory or non-inflammatory diseases, produ ced IgGs specific for C. pneumoniae intrathecally (definite multiple sclero sis versus other inflammatory neurological diseases: P = 0.027). The presen ce of intrathecal IgGs to C. pneumoniae was independent of the duration of disease and relatively stable over time. The major CSF oligoclonal IgG band s from multiple sclerosis patients with an intrathecal Ig production to C. pneumoniae did not react towards purified elementary bodies and reticulate bodies of C. pneumoniae on affinity-mediated immunoblot following isoelectr ic focusing (IEF-western blots). In contrast, the IgGs in the CSF of contro l patients with neuroborreliosis strongly reacted with their specific patho gen, Borrelia burgdorferi, by IEF-western blot analysis. Concomitant analys is of the CSF of 23 patients with a nested polymerase chain reaction for C. pneumoniae was negative in all eases. Together, our findings strongly sugg est that the immune response to C. pneumoniae is part of a polyspecific int rathecal Ig production, asis commonly observed with other pathogens. This a rgues against a specific role for C. pneumoniae in multiple sclerosis.