PMID- 16405437 OWN - NLM STAT- MEDLINE DCOM- 20060328 LR - 20061115 IS - 0902-4441 (Print) IS - 0902-4441 (Linking) VI - 76 IP - 2 DP - 2006 Feb TI - Effects of IgG and its F(ab')2 fragments of some patients with idiopathic thrombocytopenic purpura on platelet aggregation. PG - 153-9 AB - OBJECTIVES: To make humanized monoclonal antibodies by phage surface display technology, we screened out the specific anti-platelet glycoproteins (GPs) IgG antibody from patients with chronic idiopathic thrombocytopenic purpura (ITP), which can inhibit platelet aggregation. METHODS: We studied plasmas from 68 patients with ITP for the presence of IgG antibodies specific for GPIIb/IIIa and/or GPIb/IX using modified monoclonal antibody immobilization of platelet antigen assays. The IgG antibody and its F(ab')(2) fragments of the positive plasmas which could inhibit platelet aggregation function were prepared and purified. Their immunoreactivity to platelet GPs and effects on platelet function were further analyzed. RESULTS: GPIIb/IIIa- and GPIb/IX-specific antibodies were found in 21 and 19 patients, respectively. Six of them had antibodies against both GP complexes. Among the 34 positive plasmas, four with positive anti-GPIIb/IIIa autoantibody showed significant inhibition of platelet aggregation induced by adenosine diphosphate (ADP), whereas one with GPIb/IX-specific antibody inhibited ristocetin-induced platelet aggregation. The purified IgG and its F(ab')(2) fragments from two patients not only retained the ability to bind to platelet GPs but also impaired the in vitro ADP-induced platelet aggregation. CONCLUSIONS: F(ab')(2) portion of the IgG is a functional fragment, which is responsible for the autoantibody interaction with platelet GPs in ITP, and some of them also affect platelet function, which can be used to develop completely humanized anti-GPIIb/IIIa small molecular phage antibody. FAU - Chu, Xiao Xia AU - Chu XX AD - Hematology Oncology Center, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Hou, Ming AU - Hou M FAU - Peng, Jun AU - Peng J FAU - Zhu, Yuan Yuan AU - Zhu YY FAU - Ji, Xue Bin AU - Ji XB FAU - Wang, Lin AU - Wang L FAU - Zhang, Feng AU - Zhang F FAU - Ma, Dao Xin AU - Ma DX LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Haematol JT - European journal of haematology JID - 8703985 RN - 0 (Immunoglobulin Fab Fragments) RN - 0 (Immunoglobulin G) RN - 0 (Platelet Membrane Glycoproteins) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Child MH - Chronic Disease MH - Electrophoresis, Polyacrylamide Gel MH - Female MH - Humans MH - Immunoglobulin Fab Fragments/pharmacology/*therapeutic use MH - Immunoglobulin G/pharmacology/*therapeutic use MH - Male MH - Middle Aged MH - Platelet Aggregation/*drug effects MH - Platelet Membrane Glycoproteins/metabolism MH - Purpura, Thrombocytopenic, Idiopathic/*drug therapy EDAT- 2006/01/13 09:00 MHDA- 2006/03/29 09:00 CRDT- 2006/01/13 09:00 PHST- 2006/01/13 09:00 [pubmed] PHST- 2006/03/29 09:00 [medline] PHST- 2006/01/13 09:00 [entrez] AID - EJH557 [pii] AID - 10.1111/j.1600-0609.2005.00557.x [doi] PST - ppublish SO - Eur J Haematol. 2006 Feb;76(2):153-9. doi: 10.1111/j.1600-0609.2005.00557.x.