scholarly journals Posttransfusion purpura associated with an autoantibody directed against a previously undefined platelet antigen

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1458-1463 ◽  
Author(s):  
RB Stricker ◽  
BH Lewis ◽  
L Corash ◽  
MA Shuman
Keyword(s):  
Acute Phase ◽  
Platelet Destruction ◽  
Autoantibody Production ◽  
Antiplatelet Antibodies ◽  
Platelet Protein ◽  
Gp 120 ◽  
Platelet Antigen ◽  
Immunoblot Technique ◽  
Posttransfusion Purpura ◽  
Acute Phase Serum

Abstract Although alloantibody against the PLA1 platelet antigen is usually found in patients with posttransfusion purpura (PTP), the mechanism of destruction of the patient's own PLA1-negative platelets is unexplained. We used a sensitive immunoblot technique to detect antiplatelet antibodies in a patient with classic PTP. The patient's acute-phase serum contained antibodies against three proteins present in control (PLA1-positive) platelets: an antibody that bound to a previously unrecognized platelet protein of mol wt 120,000 [glycoprotein (GP) 120], antibodies that bound to PLA1 (mol wt 90,000), and an epitope of GP IIb (mol wt 140,000). The antibodies against PLA1 and GP IIb did not react with the patient's own PLA1-negative platelets, control PLA1-negative platelets, or thrombasthenic platelets. In contrast, the antibody against GP 120 recognized this protein in all three platelet preparations, but not in Bernard-Soulier or Leka (Baka)-negative platelets. Antibody against GP 120 was not detected in the patient's recovery serum, although the antibodies against PLA1 and GP IIb persisted. F(ab)2 prepared from the patient's acute-phase serum also bound to GP 120. These results suggest that in PTP, transient autoantibody production may be responsible for autologous (PLA1-negative) platelet destruction. In addition, alloantibodies against more than one platelet alloantigen may be found in this disease. The nature of the GP 120 autoantigen and the GP IIb- related alloantigen defined by our patient's serum remains to be determined.

scholarly journals Posttransfusion purpura associated with an autoantibody directed against a previously undefined platelet antigen

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1458-1463
Author(s):  
RB Stricker ◽  
BH Lewis ◽  
L Corash ◽  
MA Shuman
Keyword(s):  
Acute Phase ◽  
Platelet Destruction ◽  
Autoantibody Production ◽  
Antiplatelet Antibodies ◽  
Platelet Protein ◽  
Gp 120 ◽  
Platelet Antigen ◽  
Immunoblot Technique ◽  
Posttransfusion Purpura ◽  
Acute Phase Serum

Although alloantibody against the PLA1 platelet antigen is usually found in patients with posttransfusion purpura (PTP), the mechanism of destruction of the patient's own PLA1-negative platelets is unexplained. We used a sensitive immunoblot technique to detect antiplatelet antibodies in a patient with classic PTP. The patient's acute-phase serum contained antibodies against three proteins present in control (PLA1-positive) platelets: an antibody that bound to a previously unrecognized platelet protein of mol wt 120,000 [glycoprotein (GP) 120], antibodies that bound to PLA1 (mol wt 90,000), and an epitope of GP IIb (mol wt 140,000). The antibodies against PLA1 and GP IIb did not react with the patient's own PLA1-negative platelets, control PLA1-negative platelets, or thrombasthenic platelets. In contrast, the antibody against GP 120 recognized this protein in all three platelet preparations, but not in Bernard-Soulier or Leka (Baka)-negative platelets. Antibody against GP 120 was not detected in the patient's recovery serum, although the antibodies against PLA1 and GP IIb persisted. F(ab)2 prepared from the patient's acute-phase serum also bound to GP 120. These results suggest that in PTP, transient autoantibody production may be responsible for autologous (PLA1-negative) platelet destruction. In addition, alloantibodies against more than one platelet alloantigen may be found in this disease. The nature of the GP 120 autoantigen and the GP IIb- related alloantigen defined by our patient's serum remains to be determined.

scholarly journals Rabbit and rat C-reactive proteins bind apolipoprotein B-containing lipoproteins.

1984 ◽  
Vol 159 (2) ◽  
pp. 604-616 ◽  
Author(s):  
I F Rowe ◽  
A K Soutar ◽  
I M Trayner ◽  
M L Baltz ◽  
F C de Beer ◽  
...  
Keyword(s):  
Acute Phase ◽  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plasma Lipoproteins ◽  
Free Form ◽  
Low Density ◽  
Serum Samples ◽  
Acute Phase Serum

Immobilized rabbit and rat C-reactive protein (CRP) were found to selectively bind apolipoprotein B (apoB)-containing lipoproteins (low density lipoprotein, LDL and very low density lipoprotein, VLDL) from whole serum in a manner similar to that previously reported with human CRP. In acute phase human serum the CRP is in a free form, not complexed with lipoprotein or any other macromolecular ligand, and in acute phase serum from most rabbits fed on a normal diet the rabbit CRP was also free. However, in acute phase serum or heparinized plasma from hypercholesterolemic rabbits part or all of the CRP was found by gel filtration and immunoelectrophoretic techniques to be complexed with beta-VLDL, an abnormal apoB-containing plasma lipoprotein present in these animals. The presence of extent in different serum samples of CRP complexed with lipoprotein correlated closely with the serum apoB concentration. The formation of complexes between native, unaggregated rabbit CRP in solution and apoB-containing lipoproteins was readily demonstrable experimentally both with the isolated proteins and in whole serum. In all cases these interactions were calcium-dependent and inhibitable by free phosphoryl choline. The present findings extend earlier work in man and the rabbit and indicate that among the C-reactive proteins from different species, which are structurally highly conserved, the capacity for selective binding to apoB-containing plasma lipoproteins is also a constant feature. These interactions may therefore be related to the in vivo function of CRP in all species and this function may in turn be relevant to pathological conditions, such as atherosclerosis, in which lipoproteins are important.

scholarly journals Investigation of the solubility and the potentials for purification of serum amyloid A (SAA) from equine acute phase serum – a pilot study

2013 ◽  
Vol 6 (1) ◽  
Author(s):  
Michelle B Christensen ◽  
Jens Christian Sørensen ◽  
Stine Jacobsen ◽  
Mads Kjelgaard-Hansen
Keyword(s):  
Pilot Study ◽  
Acute Phase ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Acute Phase Serum

In search of the “LINK”: Acute Phase Serum Amyloid A

2011 ◽  
Vol 216 (2) ◽  
pp. 266-268
Author(s):  
Sidika Karakas ◽  
Rami Mortada ◽  
Clinical Fellow
Keyword(s):  
Acute Phase ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Acute Phase Serum

scholarly journals Spectrum of Ig classes, specificities, and titers of serum antiglycoproteins in chronic idiopathic thrombocytopenic purpura

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1024-1032 ◽  
Author(s):  
R He ◽  
DM Reid ◽  
CE Jones ◽  
NR Shulman
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Cytoplasmic Domain ◽  
Platelet Glycoprotein ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Secondary Phenomenon ◽  
Almost All ◽  
Posttransfusion Purpura ◽  
Detectable Serum

Abstract The characteristic decreased recovery and survival of transfused platelets in nonalloimmunized patients with idiopathic thrombocytopenic purpura (ITP) suggest that plasma antiplatelet autoantibodies (autoAbs) are present in almost all cases. Studies emphasizing reactions of IgG autoAbs with platelet glycoprotein (GP) IIb/IIIa indicate that less than 50% of ITP patients have detectable serum Abs, and that many of these Abs may not be pathogenic because they are directed against epitopes in the cytoplasmic domain of GPIIIa (Fujisawa et al, Blood 77:2207, 1991 and 79:1441, 1992). We evaluated the contribution of Ig classes other than IgG to the overall incidence of serum Abs in 47 patients with chronic ITP and the frequency of reactions with GPs IIb/IIIa, Ib/IX, IV, and Ia/IIa. Abs were further characterized by their reactions with cytosolic or exosolic GP epitopes and their titers and apparent affinities. Using immunobead techniques we found (1) anti- GPs in 85% of sera; (2) IgA and IgG Abs each in 68%, together in 51%; (3) IgM agglutinins in 15%, always with another Ab class; (4) GP Ib/IX, IIb/IIIa, IV, and Ia/IIa targets in 83%, 81%, 38%, and 28% of cases, respectively; (5) 93% of positive sera reactive with more than one GP; but GP IV or Ia/IIa never the sole target; (6) Abs against cytosolic epitopes on one or more of GPs IIIa, Ib alpha, and IIb beta in 66% of sera, always accompanied by Abs against exosolic epitopes of the same or a different GP; (7) autoAbs against cytosolic GP epitopes in 38% of 16 patients recovered from posttransfusion purpura and drug purpura; and (8) evidence that serum ITP Abs, often high-titered, saturate platelets less than alloAbs against the same GPs. Whereas Abs against external GP epitopes are a distinctive marker for ITP in 80% of patients, Abs against internal GP epitopes are likely a secondary phenomenon of platelet destruction and not pathogenic. Anti-GPs against exosolic epitopes were also found in eluates of patients platelets', suggesting that they have pathogenic significance.

Identification of critical antigen-specific mechanisms in the development of immune thrombocytopenic purpura in mice

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2520-2527 ◽  
Author(s):  
Bernhard Nieswandt ◽  
Wolfgang Bergmeier ◽  
Kirsten Rackebrandt ◽  
J. Engelbert Gessner ◽  
Hubert Zirngibl
Keyword(s):  
Platelet Activating Factor ◽  
Target Antigen ◽  
Transient Effects ◽  
Platelet Destruction ◽  
Spontaneous Bleeding ◽  
Antiplatelet Antibodies ◽  
Systemic Reactions ◽  
Linear Epitopes ◽  
Immunoglobulin G Subclass

Abstract The pathogenic effects of antiplatelet antibodies were investigated in mice. Monoclonal antibodies (mAbs) of different immunoglobulin G subclass directed against mouse GPIIbIIIa, GPIIIa, GPIbα, GPIb-IX, GPV, and CD31 were generated and characterized biochemically. MAbs against GPIb-IX, GPV, CD31, and linear epitopes on GPIIIa had mild and transient effects on platelet counts and induced no spontaneous bleeding. Anti-GPIbα mAbs induced profound irreversible thrombocytopenia (< 3% of normal) by Fc-independent mechanisms but only had minor effects on hematocrits. In contrast, injection of intact mAbs, but not F(ab)2 fragments, against conformational epitopes on GPIIbIIIa, induced irreversible thrombocytopenia, acute systemic reactions, hypothermia, decreased hematocrits, and a paradoxical loss of surface GPIIbIIIa on platelets in vivo, the latter suggesting the formation of platelet-derived microparticles. Blockage of platelet-activating factor receptors inhibited the acute reactions, but not thrombocytopenia, loss of GPIIbIIIa, and decreases in hematocrits. Repeated injections of low doses of anti-GPIIbIIIa antibodies resulted in profound thrombocytopenia and bleeding, whereas no acute systemic reactions were observed. These data strongly suggest that the identity of the target antigen recognized by antiplatelet antibodies determines the mechanisms of platelet destruction and the severity of bleeding in mice, the latter depending on previously unrecognized anti-GPIIbIIIa-specific inflammatory mechanisms.

Exacerbation of autoantibody-mediated thrombocytopenic purpura by infection with mouse viruses

Blood ◽  
2004 ◽  
Vol 104 (7) ◽  
pp. 2102-2106 ◽  
Author(s):  
Andrei Musaji ◽  
Françoise Cormont ◽  
Gaëtan Thirion ◽  
César L. Cambiaso ◽  
Jean-Paul Coutelier
Keyword(s):  
Hepatitis Virus ◽  
Severe Thrombocytopenia ◽  
Infectious Agents ◽  
Antiplatelet Antibody ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Major Mechanism ◽  
Antiplatelet Antibodies ◽  
Γ Interferon ◽  
Antigenic Mimicry

Abstract Antigenic mimicry has been proposed as a major mechanism by which viruses could trigger the development of immune thrombocytopenic purpura (ITP). However, because antigenic mimicry implies epitope similarities between viral and self antigens, it is difficult to understand how widely different viruses can be involved by this sole mechanism in the pathogenesis of ITP. Here, we report that in mice treated with antiplatelet antibodies at a dose insufficient to induce clinical disease by themselves, infection with lactate dehydrogenase-elevating virus (LDV) was followed by severe thrombocytopenia and by the appearance of petechiae similar to those observed in patients with ITP. A similar exacerbation of antiplatelet-mediated thrombocytopenia was induced by mouse hepatitis virus. This enhancement of antiplatelet antibody pathogenicity by LDV was not observed with F(ab′)2 fragments, suggesting that phagocytosis was involved in platelet destruction. Treatment of mice with clodronate-containing liposomes and with total immunoglobulin G (IgG) indicated that platelets were cleared by macrophages. The increase of thrombocytopenia triggered by LDV after administration of antiplatelet antibodies was largely suppressed in animals deficient for γ-interferon receptor. Together, these results suggest that viruses may exacerbate autoantibody-mediated ITP by activating macrophages through γ-interferon production, a mechanism that may account for the pathogenic similarities of multiple infectious agents. (Blood. 2004;104:2102-2106)

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