A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion.

Abstract

Molecular level studies on platelets deficient in collagen-induced aggregation provide evidence for identifying possible platelet collagen receptors. We investigated platelets from a patient with mild bleeding time prolongation, but otherwise normal coagulation data. Her platelets lacked collagen-induced aggregation and adhesion, but retained normal aggregation and release by other agonists. Labeling her platelets with 125I or 3H and analysis by SDS-PAGE/autoradiography showed normal levels of glycoproteins Ia, Ib, Ila, IIb, IIIa, and IV. However, there were significantly decreased incorporations of both radioactivities into a 61-kD membrane glycoprotein (GP), which was identified as GPVI from its mobility on unreduced-reduced, two-dimensional SDS-PAGE. Sugiyama et al. ( . Blood. 69: 1712 reported that the serum from an idiopathic thrombocytopenic purpura (ITP) patient contained an antibody against a 62-kD platelet protein. Our patient's platelets lacked the antigen for the ITP patient's antibody, demonstrating that the ITP serum contains a specific antibody against GPVI. The patient's parents' platelets contained -50% the normal amount of GPVI, but still had normal collagen-induced aggregation and adhesion. The patient's platelets did not bind to types I and III collagen fibrils. Our results suggest that GPVI functions as a collagen receptor.

Antibody against platelet membrane glycoprotein VI in a patient with systemic lupus erythematosus

“…Platelet lysates from our patient and a congenital GPVI-deficient patient [7] were reacted with the patient's serum. Figure 4 indicates that normal platelets have a band of about 62 kDa reacted with the patient's antibody but platelets from our patient and from a congenital GPVI-deficient patient did not show any stained band.…”

“…Analysis of platelet membrane glycoproteins. Platelet membrane glycoproteins were labeled with 125 I using the lactoperoxidase method, dissolved in 2% SDS/8 M urea, and analyzed by two-dimensional, unreducedreduced SDS-PAGE (5.5% and 7.5%), as described previously [7]. The radioactive spots were visualized with a BAS 2000 Bio-Imaging Analyzer (Fuji Film Co., Tokyo).…”

“…After washing, the membrane was incubated with peroxidase-conjugated anti-human IgG antibody and reacted with diaminobenzidine solution containing H 2 O 2 . In this experiment, platelets from a patient with congenital GPVI deficiency [7] were also analyzed for the comparison.…”

“…Postulated collagen receptors on the platelet surface include membrane glycoprotein (GP) Ia/IIa (integrin ␣ 2 ␤ 1 ) [1][2][3][4], GPIV (CD36) [5], GPVI [6,7], 85-90 kDa glycoprotein [8], and C1q receptor [9]. Recent studies have revealed that, among these proteins, GPIa/IIa and GPVI would have a physiological significance as collagen receptors on platelets [10,11].…”

“…Recent studies have revealed that, among these proteins, GPIa/IIa and GPVI would have a physiological significance as collagen receptors on platelets [10,11]. Patients with a deficiency of GPIa/IIa or GPVI show a defective platelet response to collagen [1,2,7,[12][13][14], and antibodies against either glycoprotein inhibit platelet interaction with collagen [4,6,15,16].…”