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

Abstract

Chronic intrathecal immunoglobulin (Ig) production is a hallmark of multiple sclerosis characterized by the presence of oligoclonal IgGs and, in addition, polyspecific recognition of different pathogens such as measles, rubella and herpes zoster virus. While the antigen specificity of the oligoclonal IgGs in multiple sclerosis is largely unknown, the oligoclonal IgGs arising during CNS infectious diseases are reactive against the specific pathogen. Recently, a link between Chlamydia pneumoniae and multiple sclerosis has been claimed. To test the possible role of C. pneumoniae in multiple sclerosis, 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 paired serum-CSF samples from 120 subjects (definite multiple sclerosis, 46; probable multiple sclerosis, 12; other inflammatory neurological diseases, 35; other neurological diseases, 27) by enzyme-linked immunosorbent assay, we found that 24% of all patients with definite multiple sclerosis, but only 5% of patients with other inflammatory or non-inflammatory diseases, produced IgGs specific for C. pneumoniae intrathecally (definite multiple sclerosis versus other inflammatory neurological diseases: P = 0.027). The presence of intrathecal IgGs to C. pneumoniae was independent of the duration of disease and relatively stable over time. The major CSF oligoclonal IgG bands 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 isoelectric focusing (IEF-western blots). In contrast, the IgGs in the CSF of control patients with neuroborreliosis strongly reacted with their specific pathogen, Borrelia burgdorferi, by IEF-western blot analysis. Concomitant analysis of the CSF of 23 patients with a nested polymerase chain reaction for C. pneumoniae was negative in all cases. Together, our findings strongly suggest that the immune response to C. pneumoniae is part of a polyspecific intrathecal Ig production, as is commonly observed with other pathogens. This argues against a specific role for C. pneumoniae in multiple sclerosis.

Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS

“…It has been postulated that MS is an autoimmune disease, and considerable efforts have been made to find a particular antigen associated with its physiopathology (1)(2)(3)(4). The presence of T cells, macrophages, and antibodies in MS demyelinating plaques has been established (5).…”

PCR in Diagnosis of Infection: Detection of Bacteria in Cerebrospinal Fluids

“…Therefore, the design of primers for MOMP genes must be undertaken with special care. The species-specific region of the 16S rRNA gene is also frequently utilized as a target gene in PCR for detection of C. pneumoniae (15,18 . In this regard, it is noteworthy that the detection sensitivities of the two PCRs with omp-1 versus 16S rRNA gene primers under each set of optimal conditions were different (31).…”

Lack of Serum Oligoclonal Antibody Responses to <i>Chlamydophila pneumoniae</i> in Multiple Sclerosis

“…As only 3 of the 45 patients demonstrated any serum activity against C. pneumoniae , isoelectric focusing of CSF followed by blotting onto antigen coating membrane [11] was not performed. This, however, does not discount the possibility of intrathecal production of IgG against C. pneumoniae [6]. …”

“…These findings prompted a number of further studies, the results of which have been collated by Furrows et al [4], who failed to replicate Sriram and colleagues’ findings. Sriram and colleagues original study did not investigate the serology of the MS patients or the controls, unlike later studies [5], [6]. Both of these investigations found over half of their control and MS cohorts to be positive for C. pneumoniae, whilst PCR on the corresponding CSF samples yielded no positives.…”