valentinelynx
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And here is the rebuttal by one of the authors. I had to reformat it to be readable, by hand, so apologies if it's got errors or is hard to read:
The lymphocyte transformation test for the diagnosis of Lyme borreliosis could fill a gap in the difficult diagnostics of borreliosis
V.vonBaehr
Immunology,IMDBerlin,Berlin,Germany
Correspondingauthor:V.vonBaehr,IMDBerlin,Nicolaistr.22,
12247Berlin,Germany
E-mail:v.baehr@imd-berlin.de
Sir,
We would like to comment on the article “The lymphocyte
transformation test for the diagnosis of Lyme borreliosis has
currently not been shown to be clinically useful” by Dessau
et al. in Clin Microbiol Infect. 2014 Feb 13. doi:10.1111/
1469-0691.12583.
Mr. Dessau criticizes in his article that the clinical inclusion
criteria for the assignment of the 94 patients with clinical lyme
borreliosis were not clearly defined and that the control
group consisted only of seronegative patients. This leads him
to the conclusion that due to this “selection bias” the
specificity of the LTT for borreliosis antigens maybe
overestimated.
We would like to give following comments:
Our publication indicates the fact that clinical characterization
is difficult. This is in agreement with other studies and it is
generally known that it is a problem to select a distinct
characterized patient population. However, our study did not
intend to distinguish between the immunological phenomena
of different borrelia manifestations. The aim of this study was
to investigate and confirm that the results obtained by LTT
allows a statement on the borrelia specific immune response.
As irrelevant for the study objective, we adopted clinical
diagnoses, as for example Bannwarth Syndrome, from the
patients’ health records.
The investigation of seronegative patients was performed
in order to show the specificity of the antigens used in the
LTT as it is often criticized that the detected T-cell reactivity is
not specific to borreliosis but simply a general T-cell
reactivity of patients with other inflammatory diseases. For
this reason, a seronegative healthy collective was used to
investigate the analytical specificity and to ensure that those
patients or rather probands have no borreliosis specific
memory T-lymphocytes. It is certainly correct that the
specificity is lower when also clinical healthy seropositive
patients are included. To show this point, a clinically healthy
seropositive control group (n=48) was investigated as well,
as shown in table1. And indeed, with 91.6% thes pecificity
was lower than the specificity of the seronegative group,
however, this is clearly shown and also addressed in the
discussion section.
Despite the criticism regarding our patient selection,the
quintessences should be accepted:
1.The fact that 1.3% of healthy seronegative (and therefore
very likely not infected) and only 8.4% of healthy seropos-
itive patients showed positive results speaks for a high
analytical specificity.
2. The fact that 92.1% of patients in the early infection phase
and 53.3% of patients with late manifestations forms showed
a decline or negative LTT results under antibiotic treatment
argues for the specificity of the analysis, because it is not
explainable why antibiotic treatment should influence an
unspecific T-cell reactivity.
In our article we emphasize that clinical evaluation is
essential for diagnosis, but that the LTT is able to give
additional evidence. Mr.Dessau did not address the available
scientific literature regarding LTT in his comment. However,
this would have shown that other authors confirm our results
[1–5].
It is important to ensure the specificity of the
technically sophisticated LTT. This strongly depends on the
selection of antigens. The specificity must be tested prior to
use for each antigen lot on an adequate amount of healthy
people. The LTT is, provided that it is validated lege artis by
the performing laboratory, are a reproducible laboratory method
which should be used as extension to serological methods
and when the clinical picture does not give sufficient certainty.
The LTT should not replace serological methods and clinical
evaluation.
TransparencyDeclaration
The author has no conflicting interest to declare.
References
1.KrauseA,BradeV,SchoernerC,SolbachW,KaldenJR,BurmesterGR.
TcellproliferationinducedbyBorreliaburgdorferiinpatientswithLyme
borreliosis.ArthritisRheum1991;34:393–402.
2.SchemppC,BocklageH,OwsianowskiM,LangeR,OrfanosCE,
GollnickH.InvivoundinvitroNachweiseinerBorrelieninfektionbei
einermorphea
€
ahnlichenHautver
€
anderungmitnegativerBorreliense-
rologie.Hautarzt1993;44:14–18.
3.BreierF,KladeH,StanekGetal.Lymphoproliferativeresponsesto
Borreliaburgdorferiincircumscribedscleroderma.BrJDerm atol1996;
134:285–291.
ª2014TheAuthors
The lymphocyte transformation test for the diagnosis of Lyme borreliosis could fill a gap in the difficult diagnostics of borreliosis
V.vonBaehr
Immunology,IMDBerlin,Berlin,Germany
Correspondingauthor:V.vonBaehr,IMDBerlin,Nicolaistr.22,
12247Berlin,Germany
E-mail:v.baehr@imd-berlin.de
Sir,
We would like to comment on the article “The lymphocyte
transformation test for the diagnosis of Lyme borreliosis has
currently not been shown to be clinically useful” by Dessau
et al. in Clin Microbiol Infect. 2014 Feb 13. doi:10.1111/
1469-0691.12583.
Mr. Dessau criticizes in his article that the clinical inclusion
criteria for the assignment of the 94 patients with clinical lyme
borreliosis were not clearly defined and that the control
group consisted only of seronegative patients. This leads him
to the conclusion that due to this “selection bias” the
specificity of the LTT for borreliosis antigens maybe
overestimated.
We would like to give following comments:
Our publication indicates the fact that clinical characterization
is difficult. This is in agreement with other studies and it is
generally known that it is a problem to select a distinct
characterized patient population. However, our study did not
intend to distinguish between the immunological phenomena
of different borrelia manifestations. The aim of this study was
to investigate and confirm that the results obtained by LTT
allows a statement on the borrelia specific immune response.
As irrelevant for the study objective, we adopted clinical
diagnoses, as for example Bannwarth Syndrome, from the
patients’ health records.
The investigation of seronegative patients was performed
in order to show the specificity of the antigens used in the
LTT as it is often criticized that the detected T-cell reactivity is
not specific to borreliosis but simply a general T-cell
reactivity of patients with other inflammatory diseases. For
this reason, a seronegative healthy collective was used to
investigate the analytical specificity and to ensure that those
patients or rather probands have no borreliosis specific
memory T-lymphocytes. It is certainly correct that the
specificity is lower when also clinical healthy seropositive
patients are included. To show this point, a clinically healthy
seropositive control group (n=48) was investigated as well,
as shown in table1. And indeed, with 91.6% thes pecificity
was lower than the specificity of the seronegative group,
however, this is clearly shown and also addressed in the
discussion section.
Despite the criticism regarding our patient selection,the
quintessences should be accepted:
1.The fact that 1.3% of healthy seronegative (and therefore
very likely not infected) and only 8.4% of healthy seropos-
itive patients showed positive results speaks for a high
analytical specificity.
2. The fact that 92.1% of patients in the early infection phase
and 53.3% of patients with late manifestations forms showed
a decline or negative LTT results under antibiotic treatment
argues for the specificity of the analysis, because it is not
explainable why antibiotic treatment should influence an
unspecific T-cell reactivity.
In our article we emphasize that clinical evaluation is
essential for diagnosis, but that the LTT is able to give
additional evidence. Mr.Dessau did not address the available
scientific literature regarding LTT in his comment. However,
this would have shown that other authors confirm our results
[1–5].
It is important to ensure the specificity of the
technically sophisticated LTT. This strongly depends on the
selection of antigens. The specificity must be tested prior to
use for each antigen lot on an adequate amount of healthy
people. The LTT is, provided that it is validated lege artis by
the performing laboratory, are a reproducible laboratory method
which should be used as extension to serological methods
and when the clinical picture does not give sufficient certainty.
The LTT should not replace serological methods and clinical
evaluation.
TransparencyDeclaration
The author has no conflicting interest to declare.
References
1.KrauseA,BradeV,SchoernerC,SolbachW,KaldenJR,BurmesterGR.
TcellproliferationinducedbyBorreliaburgdorferiinpatientswithLyme
borreliosis.ArthritisRheum1991;34:393–402.
2.SchemppC,BocklageH,OwsianowskiM,LangeR,OrfanosCE,
GollnickH.InvivoundinvitroNachweiseinerBorrelieninfektionbei
einermorphea
€
ahnlichenHautver
€
anderungmitnegativerBorreliense-
rologie.Hautarzt1993;44:14–18.
3.BreierF,KladeH,StanekGetal.Lymphoproliferativeresponsesto
Borreliaburgdorferiincircumscribedscleroderma.BrJDerm atol1996;
134:285–291.
ª2014TheAuthors
