PMID- 33797185
OWN - NLM
STAT- MEDLINE
DCOM- 20220201
LR  - 20220201
IS  - 1552-4930 (Electronic)
IS  - 1552-4922 (Linking)
VI  - 101
IP  - 1
DP  - 2022 Jan
TI  - Basophil activation test: Assay precision and BI 1002494 SYK inhibition in 
      healthy and mild asthmatics.
PG  - 86-94
LID - 10.1002/cyto.a.24338 [doi]
AB  - BACKGROUND: Application of basophil activation test (BAT) in clinical trials 
      requires assay validity. Whether assay variability differs between healthy and 
      asthmatic subjects is mostly unknown. This study compares basophil stimulation 
      using blood from healthy and asthmatic subjects with or without inhibition of 
      spleen tyrosine kinase (SYK). METHODS: Whole blood of healthy and mild asthmatic 
      subjects was stimulated with anti-dinitrophenyl (DNP) IgE/DNP bovine serum 
      albumin and anti-IgE. Basophil activation was detected by CD63 and CD203c 
      expression. CD63 expression levels were compared with serum IgE levels. Three 
      operators repeated experiments with three subjects each from both groups at 
      3 days to observe assay precision. The effect of the SYK inhibitor BI 1002494 was 
      assessed in BAT for both healthy and asthmatic subjects. RESULTS: BAT was 
      reproducible in both groups. Acceptance criteria of <25% CV were mostly 
      fulfilled. Stimulation with anti-DNP (p < 0.001, r = -0.80) but not anti-IgE 
      (p = 0.74, r = 0.05) was related to serum IgE with levels > 200 IU/ml limiting 
      anti-DNP stimulation. BI 1002494 IC(50) values were 497 nM and 1080 nM in healthy 
      and 287 nM and 683 nM in asthmatics for anti-DNP and anti-IgE stimulation, 
      respectively. CONCLUSION: BAT, performed with blood from healthy or asthmatic 
      subjects, is a robust test for the measurement of a physiological response in 
      clinical trials. Blood from asthmatic donors with serum IgE > 200 IU/ml is less 
      feasible when using anti-DNP stimulation. SYK inhibition was not affected by 
      disease status.
CI  - (c) 2021 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf 
      of International Society for Advancement of Cytometry.
FAU - Carstensen, Saskia
AU  - Carstensen S
AUID- ORCID: 0000-0002-3532-9311
AD  - Department of Biomarker Analysis and Development, Fraunhofer Institute of 
      Toxicology and Experimental Medicine, Hannover, Germany.
FAU - Benediktus, Ewald
AU  - Benediktus E
AD  - Department of Translational Medicine and Clinical Pharmacology, Boehringer 
      Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
FAU - Litzenburger, Tobias
AU  - Litzenburger T
AD  - Department of Translational Medicine and Clinical Pharmacology, Boehringer 
      Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
FAU - Hohlfeld, Jens M
AU  - Hohlfeld JM
AD  - Division of Airway Research, Fraunhofer Institute of Toxicology and Experimental 
      Medicine, Hannover, Germany.
AD  - Member of the German Center for Lung Research, Hannover, Germany.
AD  - Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
FAU - Muller, Meike
AU  - Muller M
AD  - Department of Biomarker Analysis and Development, Fraunhofer Institute of 
      Toxicology and Experimental Medicine, Hannover, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210401
PL  - United States
TA  - Cytometry A
JT  - Cytometry. Part A : the journal of the International Society for Analytical 
      Cytology
JID - 101235694
RN  - 0 (BI 1002494)
RN  - 0 (Naphthyridines)
RN  - 0 (Pyrrolidinones)
RN  - 0 (Tetraspanin 30)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
SB  - IM
MH  - *Basophil Degranulation Test
MH  - Basophils
MH  - Flow Cytometry
MH  - Humans
MH  - *Immunoglobulin E
MH  - Naphthyridines
MH  - Pyrrolidinones
MH  - Syk Kinase
MH  - Tetraspanin 30
OTO - NOTNLM
OT  - CD203c
OT  - CD63
OT  - SYK inhibitor
OT  - asthma
OT  - basophil activation test
OT  - flow cytometry
OT  - human basophil
OT  - serum IgE
OT  - validation
EDAT- 2021/04/03 06:00
MHDA- 2022/02/02 06:00
CRDT- 2021/04/02 06:54
PHST- 2021/02/09 00:00 [revised]
PHST- 2020/12/14 00:00 [received]
PHST- 2021/03/17 00:00 [accepted]
PHST- 2021/04/03 06:00 [pubmed]
PHST- 2022/02/02 06:00 [medline]
PHST- 2021/04/02 06:54 [entrez]
AID - 10.1002/cyto.a.24338 [doi]
PST - ppublish
SO  - Cytometry A. 2022 Jan;101(1):86-94. doi: 10.1002/cyto.a.24338. Epub 2021 Apr 1.