DETECTION OF BORRELIA BURGDORFERI-SPECIFIC ANTIGEN IN ANTIBODY-NEGATIVE CEREBROSPINAL FLUID IN NEUROLOGIC 
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 DETECTION OF BORRELIA BURGDORFERI-SPECIFIC ANTIGEN IN ANTIBODY-NEGATIVE CEREBROSPINAL FLUID IN NEUROLOGIC

"........  Until there is widespread availability of
effective tests to document presence of this spirochete, diagnosis and
treatment decisions in neurologic Lyme disease must continue to be based
on reasonable clinical judgment that takes into account the possibility of
a growing spectrum of presentations in Lyme disease....."

DETECTION OF BORRELIA BURGDORFERI-SPECIFIC ANTIGEN IN ANTIBODY-NEGATIVE
CEREBROSPINAL FLUID IN NEUROLOGIC
                                    LYME DISEASE

P.K. Coyle, MD; S.E. Schutzer, MD; Z. Deng, MS: L.B. Krupp. MD; A.L.
Belman, MD; J.L. Benach, PhD: aand B.J. Luft, MD

            NEUROLOGY 45 November 1995;pp. 2010-2014

Article abstract - OBJECTIVE: to determine the potential of detection in
CSF of specific Borellia burgdorferi antigen, OspA, as a marker of
infection in neurologic Lyme disease and compare this with the detection
of antibody.  DESIGN: CSF from 83 neurologic patients in an area highly
endemic for Lyme disease was examined prospectively for (1) OspA by
antigen capture ELISA and Western blot employing monoclonal antibodies,
and for (2) B. burgdorferi antibodies by ELISA,  RESULTS:  Of the 35 of 83
(42%) patients who were positive for OspA antigen in their CSF, 15 (43%)
were antigen positive despite being antibody-negative in CSF.  Seven of
these 15 (47%) had otherwise normal routine CSF analyses.  Six of these 15
(40%) patients met strict CDC surveillance critera for Lyme disease: four
(27%) patients had seroconversion coincedent with new neurologic problems:
and three (20%) with characteristic syndromes for Lyme diseasewere
seronegative, but had complexed antibody to B. burgdorferi.  The final two
patients (13%) were seropositive and had unexplained neurologic problems
not characteristic of Lyme disease.  CONCLUSIONS:  B. burgdorferi antigen
can be detected in CSF that is otherwise normal by conventional
methodology, and can be present without positive CSF antibody.  Since CSF
antigen implies intrathecal seeding of the infection, the diagnosis of
neurologic infection by B. burgdorferi should not be excluded solely on
the basis of normal routine CSF or negative CSF antibody analyses.

BACKGROUND:  The full spectrum of Lyme disese , and neurologic Lyme
disease in particular has yet to be defined.  This disease, caused by the
tick-borne spirochete Borrelia burgodorferi, is now the most common
vector-borne infection in the United States.  Prompt and precise diagnosis
is difficult because basic microbiologic tests such as culture and
staining have not been useful, on a broad scale, to document the presence
of the spirochete in a body fluid. Instead, detection of specific
antibodies to B burgodorferi in {*filter*} and CSF is commonly used to support
or refute a clinical suspicion of infection.  Many of the commercially
available assays have been plagued by lack of sensitivity, specificity,
and reproducibility.  Furthermore, the absence of free antibodies to B
burgdorferi components has been documented in well-characterized
erythemia-migrans-positive cases of Lyme disease, including those with
prominent neurologic involvement.

Many antigens of B burgdorferi share common determinants with other
bacteria and their products.  However, some are unique to Bb.,and
consequently the detection of these specific antigens or antibodies to
them has high diagnostic potential.  One such abundant protein is the
outer surface protein A (OspA), a 31-kD transmembrane lipoprotein.  There
are data to suggest that the spirochete sheds outer surface membrane
"blebs" which contain OspA antigen, into surrounding fluids.  In earlier
work, we were able to detect antigen-like material consistent with OspA in
the CSF of patients with neurologic Lyme disease.  We have also
demonstrated that humans have the immunologic potential to recognize this
protein within the first days to weeks of infection and produce antibody
to it.  This antibody and its corresponding target antigen may frequently
be detected with immune complexes.

In this study, we report our investigation of a prospectively gathered
group of patients referred because neurologic Lyme disease was in the
differential diagnosis.  We analyzed CSF samples by ELISA and Western blot
for CSF OspA antigen and by ELISA CSF anti-B burgdorferi antibodies.

DISCUSSION SUMMARY:  In summary, Bb. antigen can be detected in CSF that
is otherwise normal by conventional methodology and can be present without
positive CSF antibodies.  In 27% of the cases, antibodies to Bb could be
detected after dissociation of immune complexes.  Since CSF antigen
implies intrathecal seeding of the infection, the diagnosis of neurologic
infection by Bb should not be excluded based solely on normal CSF or
negative CSF antibody analyses.  This is particularly important because
different therapeutic approaches, such as antibiotics that penetrate the
CNS, are likely to be used.  Until there is widespread availability of
effective tests to document presence of this spirochete, diagnosis and
treatment decisions in neurologic Lyme disease must continue to be based
on reasonable clinical judgment that takes into account the possibility of
a growing spectrum of presentations in Lyme disease.

Address correspondence and reprint requests to:

Dr. P.K. Coyle, Department of Neurology, HSC T-12, SUNY at Stony Brook, NY
11794    USA.



Sun, 23 May 2004 10:06:59 GMT
 
 [ 1 post ] 

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