PMID- 34287950
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20220408
IS  - 1398-9995 (Electronic)
IS  - 0105-4538 (Linking)
VI  - 77
IP  - 3
DP  - 2022 Mar
TI  - Identification of novel biomarkers to distinguish bradykinin-mediated angioedema 
      from mast cell-/histamine-mediated angioedema.
PG  - 946-955
LID - 10.1111/all.15013 [doi]
AB  - BACKGROUND: The pathophysiology of the underlying paroxysmal permeability 
      disturbances in angioedema (AE) is not well understood. METHODS: To identify 
      clinical and laboratory parameters specific for a certain AE subtype, 40 AE 
      patients were prospectively enrolled: 15 hereditary (HAE), 13 ACE-inhibitor 
      induced (ACE-AE), and 12 mast cell-mediated without wheals in chronic spontaneous 
      urticaria (CSU-AE). Ten healthy subjects served as controls. Serum levels of 
      markers indicating activation of the ficolin-lectin pathway, of endothelial 
      cells, or those indicating impairment of vascular integrity or inflammation were 
      assessed by enzyme-linked immunosorbent assay. RESULTS: New routine clinical 
      diagnostic criteria could not be identified, not even for distinguishing 
      bradykinin-mediated (BK-) AE (ie, HAE and ACE-AE) from mast 
      cell-/histamine-mediated CSU-AE. However, FAP-alpha and tPA were significantly 
      increased in all AE compared to controls. In HAE, FAP- alpha, tPA, uPAR, pentraxin-3, 
      Tie-2, sE-selectin, and VE-cadherin were significantly increased compared to 
      controls. In HAE compared to CSU-AE and ACE-AE, sE-Selectin, Tie-2, and 
      VE-Cadherin were significantly increased, whereas for Ang-2 the difference was 
      significant compared to CSU-AE only. Tie-2 correlated strongly negatively with 
      C4, C1-INH activity, and C1-INH function. CONCLUSIONS: This study is the first to 
      compare HAE, ACE-AE, and CSU-AE. Although significance is limited by small sample 
      size, Tie-2 was identified as a new promising biomarker candidate for HAE. FAP- alpha 
      and tPA might serve as a marker for AE in general, whereas sE-selectin and Ang-2 
      were increased in BK-AE only. Our results add information to the role of 
      endothelial dysfunction and serine proteases in different AE subtypes.
CI  - (c) 2021 The Authors. Allergy published by European Academy of Allergy and Clinical 
      Immunology and John Wiley & Sons Ltd.
FAU - Bindke, Gesa
AU  - Bindke G
AD  - Department of Dermatology and Allergy, Hannover Medical School, Comprehensive 
      Allergy Center, Hereditary Angioedema center for rare diseases, Hannover, 
      Germany.
FAU - Gehring, Manuela
AU  - Gehring M
AD  - Department of Dermatology and Allergy, Hannover Medical School, Comprehensive 
      Allergy Center, Hereditary Angioedema center for rare diseases, Hannover, 
      Germany.
FAU - Wieczorek, Dorothea
AU  - Wieczorek D
AD  - Department of Dermatology and Allergy, Hannover Medical School, Comprehensive 
      Allergy Center, Hereditary Angioedema center for rare diseases, Hannover, 
      Germany.
FAU - Kapp, Alexander
AU  - Kapp A
AD  - Department of Dermatology and Allergy, Hannover Medical School, Comprehensive 
      Allergy Center, Hereditary Angioedema center for rare diseases, Hannover, 
      Germany.
FAU - Buhl, Timo
AU  - Buhl T
AUID- ORCID: 0000-0002-3139-129X
AD  - Department of Dermatology, Venerology and Allergology, University Medical Centre 
      Gottingen, Gottingen, Germany.
FAU - Wedi, Bettina
AU  - Wedi B
AUID- ORCID: 0000-0002-9868-6308
AD  - Department of Dermatology and Allergy, Hannover Medical School, Comprehensive 
      Allergy Center, Hereditary Angioedema center for rare diseases, Hannover, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210728
PL  - Denmark
TA  - Allergy
JT  - Allergy
JID - 7804028
RN  - 0 (Biomarkers)
RN  - 0 (Complement C1 Inhibitor Protein)
RN  - 0 (Selectins)
RN  - 0 (Transcription Factors)
RN  - 820484N8I3 (Histamine)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - *Angioedema/diagnosis
MH  - *Angioedemas, Hereditary/diagnosis
MH  - Biomarkers
MH  - Bradykinin/metabolism
MH  - *Chronic Urticaria
MH  - Complement C1 Inhibitor Protein
MH  - Endothelial Cells/metabolism
MH  - Histamine/metabolism
MH  - Humans
MH  - Mast Cells/metabolism
MH  - Selectins/metabolism
MH  - Transcription Factors/metabolism
OTO - NOTNLM
OT  - Tie-2
OT  - angioedema
OT  - biomarker
OT  - bradykinin
OT  - hereditary angioedema
EDAT- 2021/07/22 06:00
MHDA- 2022/04/09 06:00
CRDT- 2021/07/21 13:14
PHST- 2021/05/07 00:00 [received]
PHST- 2021/07/09 00:00 [accepted]
PHST- 2021/07/22 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
PHST- 2021/07/21 13:14 [entrez]
AID - 10.1111/all.15013 [doi]
PST - ppublish
SO  - Allergy. 2022 Mar;77(3):946-955. doi: 10.1111/all.15013. Epub 2021 Jul 28.