was "degranulation" now "why flow?"

From: Nebe, Thomas C. (thomas.nebe@ikc.ma.uni-heidelberg.de)
Date: Mon Nov 11 2002 - 13:08:15 EST


Dear Dr. Aber,
Dear Dr. Prussin,
 
I want to give a few comments about measuring basophil degranulation by flow
and CD63 as my brother forwarded me your discussion on the Purdue server.
 
We have done the classical histamin release test practically in our lab for
a long time (checked two different suppliers) and developed that flow test
because of the drawbacks of the histamin immunoassays. We have tested
several dyes and many surface molecules for basophils and decided to use
gp55, now called CD63 as this approach came up with the best results. A
french group did it independently in parallel (Sainte-Laudy). We also
carefully validated our assay against the histamin release assay. BD and a
swiss company from de Weck just released a copy of that test.
 
Our clinical problems to solve were to discriminate bee and wasp venom
allergy and to check for latex allergy, where we had a lot of sesitized
persons among our 4000 employees, where the specific IgE test did not work
properly.
 
The ELISA is less reliable because of variations of spontaneous histamin
release and several allergens were proven to contain suffcient amounts of
histamin that we just tried to measure. Contaminating bacteria in the raw
material are able to convert histidin to histamin. The ELISA requires batch
testing and it takes 2 days as you have to convert histamin to a derivative
that the monoclonal can detect as you cannot immunize with histamin. The day
to day variability is considerable.
 
Concerning the referees, there are already enough papers out using that
method. Don`t be afraid. Of course, the calculations are different as you do
not measure the same thing. But you could ratio the spontaneous percentage
of CD63 expression and the stimulated % of CD63 if you like to. The
presented conversion from percentages of release into a drop in mean
channels is hard to follow.
 
Using a cell line, the basotest kit might be overdone as it addresses whole
blood from patients and CD63 may be sufficient for the homogeneous
pouplation (CD63 has already been used for mast cell lines).  We also
compared CD203 from Dr. Buehring that also identify basophils but the shift
in expression density of this marker upon degranulation is not sensitive
enough. The spontaneous histamin release from dead cells from day to day
might be a concern and might favour an antibody staining.
 
So, even appreciating the theoretical considerations from Dr. Prussin, from
a practical point of view, the flow assay makes some sense. It might not be
the last answer to the intriguing challenge of clinical tests for
hypersensitivity.
 
Best regards
Thomas Nebe
 
Dr. C. Thomas Nebe 
Facharzt für Laboratoriumsmedizin und Klinischer Chemiker 
Institut für Klinische Chemie 
Zentrallabor des 
Universitätsklinikum Mannheim
Theodor-Kutzer-Ufer 1-3 
D-68167 Mannheim 
Tel. +49 621 383-3485 
FAX +49 621 383-733485 
thomas.nebe@ikc.ma.uni-heidelberg.de 
http://www.ma.uni-heidelberg.de/inst/ikc
<http://www.ma.uni-heidelberg.de/inst/ikc>  
 
 



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