PMID- 22472781 OWN - NLM STAT- MEDLINE DCOM- 20150409 LR - 20181023 IS - 0048-7449 (Print) IS - 0048-7449 (Linking) VI - 64 IP - 1 DP - 2012 Mar 19 TI - In vitro effect of anti-beta(2) glycoprotein I antibodies on P-selectin expression, a marker of platelet activation. PG - 35-9 LID - 10.4081/reumatismo.2012.35 [doi] AB - OBJECTIVE: Antiphospholipid antibodies (aPL) associated with thrombembolic events and/or pregnancy morbidity characterize the so-called antiphospholipid syndrome (APS). Beta2glycoprotein I (beta2GPI) represents the major target antigen for aPL, but the pathogenic role of anti-beta2GPI antibodies (abeta2GPI) is still unclear. Some authors assume they play a role in activating platelets. The effects of abeta2GPI antibodies on platelet P-selectin expression were evaluated in this study. METHODS: Abeta2GPI antibodies in the plasma of a pregnant APS patient were isolated by affinity chromatography during two different stages (catastrophic and quiescent) of the disease. Gel filtered platelets (100,000/mul) from healthy volunteers were incubated with beta2-GPI (20 mug/ml) and with different concentrations (5, 25 e 50 mug/ml) of abeta2GPI antibodies. P-selectin surface expression on platelets was assessed by flow cytometry using a specific fluorescent antibody directed against P-selectin. RESULTS: Abeta2GPI antibodies induced platelet activation only in the presence of thrombin receptor activator for peptide 6 (TRAP-6), a platelet agonist, at a subthreshold concentration. Abeta2GPI antibody enhancement on platelet surface P-selectin expression was stronger in the catastrophic than in the quiescent phase of the disease (47% versus 15%). CONCLUSIONS: TRAP-6 dependent platelet activation by abeta2GPI antibodies is consistent with the "two hit" pathogenetic hypothesis for thrombosis. Abeta2GPI antibodies induce higher platelet P-selectin expression during the active rather than in the acute phases. FAU - Bontadi, A AU - Bontadi A AD - Cattedra e U.O.C. di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Universita di Padova, Italy. agnese.bontadi@unipd.it FAU - Ruffatti, A AU - Ruffatti A FAU - Giannini, S AU - Giannini S FAU - Falcinelli, E AU - Falcinelli E FAU - Tonello, M AU - Tonello M FAU - Hoxha, A AU - Hoxha A FAU - Gresele, P AU - Gresele P FAU - Punzi, L AU - Punzi L LA - eng PT - Comparative Study PT - Journal Article DEP - 20120319 PL - Italy TA - Reumatismo JT - Reumatismo JID - 0401302 RN - 0 (Autoantibodies) RN - 0 (Autoantigens) RN - 0 (P-Selectin) RN - 0 (Peptide Fragments) RN - 0 (beta 2-Glycoprotein I) RN - 0 (thrombin receptor peptide (42-47)) SB - IM MH - Acute Disease MH - Adult MH - Antiphospholipid Syndrome/*blood/complications/immunology MH - Autoantibodies/immunology/isolation & purification/*pharmacology MH - Autoantigens/*immunology/isolation & purification MH - Chromatography, Affinity MH - Female MH - Flow Cytometry MH - Humans MH - In Vitro Techniques MH - P-Selectin/*biosynthesis/genetics MH - Peptide Fragments/pharmacology MH - *Platelet Activation MH - Pregnancy MH - Pregnancy Complications/*blood/immunology MH - Pregnancy Complications, Hematologic/blood/etiology/immunology MH - Thrombophilia/blood/*etiology/immunology MH - beta 2-Glycoprotein I/*immunology/isolation & purification/pharmacology EDAT- 2012/04/05 06:00 MHDA- 2015/04/10 06:00 CRDT- 2012/04/05 06:00 PHST- 2011/11/21 00:00 [received] PHST- 2011/11/30 00:00 [accepted] PHST- 2012/04/05 06:00 [entrez] PHST- 2012/04/05 06:00 [pubmed] PHST- 2015/04/10 06:00 [medline] AID - reumatismo.2012.35 [pii] AID - 10.4081/reumatismo.2012.35 [doi] PST - epublish SO - Reumatismo. 2012 Mar 19;64(1):35-9. doi: 10.4081/reumatismo.2012.35.