PMID- 31018220
OWN - NLM
STAT- MEDLINE
DCOM- 20191220
LR  - 20211204
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Linking)
VI  - 119
IP  - 7
DP  - 2019 Jul
TI  - Platelet Activation by Antiphospholipid Antibodies Depends on Epitope Specificity 
      and is Prevented by mTOR Inhibitors.
PG  - 1147-1153
LID - 10.1055/s-0039-1685453 [doi]
AB  - Antiphospholipid antibodies (aPL) have been reported to activate platelets. This 
      is considered to be one of the pathogenic properties of aPL. Even though aPL 
      heterogeneity is quite well established, little is known, if the ability to 
      activate platelets is common to all aPL or depends on antigen specificity. To 
      further study this issue, we analyzed the ability of three human monoclonal aPL 
      with distinctly different antigenic specificities to activate platelets in vitro. 
      The results obtained with human monoclonal aPL were validated with immunoglobulin 
      G (IgG) fractions obtained from patients with antiphospholipid syndrome (APS). A 
      co-factor-independent human monoclonal anticardiolipin aPL had no discernible 
      effect on human platelets. Two monoclonal aPL reactive against beta2 glycoprotein I 
      (beta2GPI) induced platelet aggregation, integrin alphaIIbbeta3 activation and P-selectin 
      surface expression. These data could be confirmed with patient IgG fractions 
      which could only induce aggregation, if they had anti-beta2GPI activity. Anti-beta2GPI 
      aPL-induced platelet activation depended on interaction of aPL with the low 
      affinity Fcgamma-receptor IIa on the platelet surface. It was completely abolished by 
      pretreatment of platelet-rich plasma with the mechanistic target of rapamycin 
      (mTOR) inhibitors rapamycin or everolimus. This extends previous data showing 
      that mTOR is involved in signaling of anti-beta2GPI in monocytes and endothelial 
      cells. In conclusion, anti-beta2GPI aPL activate platelets while 
      co-factor-independent anticardiolipin aPL have no effect. mTOR is involved in 
      this signaling process which has implications beyond APS, because so far the role 
      of mTOR signaling in platelets is incompletely explored and requires further 
      study.
CI  - Georg Thieme Verlag KG Stuttgart . New York.
FAU - Hollerbach, Anne
AU  - Hollerbach A
AD  - Institute of Clinical Chemistry and Laboratory Medicine, University Medical 
      Center Mainz, Mainz, Germany.
AD  - Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, 
      Germany.
FAU - Muller-Calleja, Nadine
AU  - Muller-Calleja N
AD  - Institute of Clinical Chemistry and Laboratory Medicine, University Medical 
      Center Mainz, Mainz, Germany.
AD  - Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, 
      Germany.
FAU - Ritter, Svenja
AU  - Ritter S
AD  - Institute of Clinical Chemistry and Laboratory Medicine, University Medical 
      Center Mainz, Mainz, Germany.
FAU - Hauser, Friederike
AU  - Hauser F
AD  - Institute of Clinical Chemistry and Laboratory Medicine, University Medical 
      Center Mainz, Mainz, Germany.
FAU - Canisius, Antje
AU  - Canisius A
AD  - Institute of Clinical Chemistry and Laboratory Medicine, University Medical 
      Center Mainz, Mainz, Germany.
FAU - Orning, Carolin
AU  - Orning C
AD  - Institute of Clinical Chemistry and Laboratory Medicine, University Medical 
      Center Mainz, Mainz, Germany.
FAU - Jurk, Kerstin
AU  - Jurk K
AD  - Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, 
      Germany.
FAU - Lackner, Karl J
AU  - Lackner KJ
AD  - Institute of Clinical Chemistry and Laboratory Medicine, University Medical 
      Center Mainz, Mainz, Germany.
LA  - eng
PT  - Journal Article
DEP - 20190424
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Antibodies, Antiphospholipid)
RN  - 0 (Autoantibodies)
RN  - 0 (Epitopes)
RN  - 0 (Epitopes, B-Lymphocyte)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 0 (beta 2-Glycoprotein I)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antibodies, Antiphospholipid/metabolism
MH  - Antiphospholipid Syndrome/drug therapy/*immunology
MH  - Autoantibodies/metabolism
MH  - Blood Platelets/*physiology
MH  - Cells, Cultured
MH  - Epitopes/*metabolism
MH  - Epitopes, B-Lymphocyte/*metabolism
MH  - Everolimus/pharmacology/therapeutic use
MH  - Humans
MH  - Platelet Aggregation/*drug effects
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/metabolism
MH  - Signal Transduction
MH  - Sirolimus/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
MH  - beta 2-Glycoprotein I/immunology
COIS- None declared.
EDAT- 2019/04/25 06:00
MHDA- 2019/12/21 06:00
CRDT- 2019/04/25 06:00
PHST- 2019/04/25 06:00 [pubmed]
PHST- 2019/12/21 06:00 [medline]
PHST- 2019/04/25 06:00 [entrez]
AID - 10.1055/s-0039-1685453 [doi]
PST - ppublish
SO  - Thromb Haemost. 2019 Jul;119(7):1147-1153. doi: 10.1055/s-0039-1685453. Epub 2019 
      Apr 24.