Page 74 - Human Lyme Neuroborreliosis

58 David S. Younger

tissues other than CNS relative to animals who mounted a typically strong IgG
response to disseminated infection [16]. Corticosteroid treatment resulted in
interference with isotype switching in NHP providing evidence that anti- B.
burgdorferi IgG antibody was more effective than IgM antibody in decreasing
the spirochetal load in infected animals.

A third hypothesis was that inflammation was highly correlated with the
presence of spirochetes. This was not entirely accurate as the cerebrum had a
high load of spirochetes relative to other tissues but no inflammation whereas
other organs such as skeletal muscle had very high levels of inflammation with
spirochete loads similar to that of the brain.

A fourth hypothesis was that selective intrathecal IgG antibody production
would not be prominent despite the presence of large amounts of B.
burgdorferi within the CNS, and that proved to be accurate. The intrathecal
IgG antibody production of the N40Br B. burgdorferi sensu stricto strain of
the pathogen was not prominent at all [17] in contrast to the pathogen of Lyme
meningitis in Europe, B. garnii in which selective intrathecal IgG antibody
was a consistent feature [18]. In light of the similar values of serum and CSF
IgG, when each were adjusted to the same concentration of IgG and there was
no evidence of intrathecal antibody synthesis, it was conjectured that diffusion
from the serum into the CSF accounted for the impression of selective
intrathecal production in a prior study [5]. In another set of NHP experiments,
Cadavid and colleagues [19] employed the PCR-ELISA of the OspA gene
followed by immunohistochemistry to study the localization and numbers of
spirochetes in CNS and PNS tissues in three groups of animals: infected
immunosuppressed, infected immunocompetent, and uninfected controls. An
unexpired finding was that treatment with corticosteroids resulted in
persistence of high levels of specific antibodies of the IgM isotype, which
were unable to eradicate the infection from any of the tissues examined. OspA
was down-regulated early after infection and OspC was down-regulated in
chronic infection while expression of flagellin was maintained. Employing
PCR-ELISA, their investigations were able to detect as little as 10 to 30 fg of
B. burgdorferi DNA per 500 ng of tissue DNA. The amount of OspA DNA
was significantly higher in all tissues from immunosuppressed animals
compared with immunocompetent animals. PCR-ELISA showed that B.
burgdorferi DNA was present in most tissues examined from all inoculated
animals but highest in the immunosuppressed group. Spirochetes were found
in the leptomeninges, motor and sensory nerve roots and dorsal root ganglia
but not in spinal cord parenchyma, with the highest counts in the lumbar roots
and cauda equina. Spirochetes were also found in the perineurium,

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