Effect of maternal anti-HPA-1a antibodies and polyclonal IVIG on the activation status of vascular endothelial cells

Radder, Celine M.; Beekhuizen, Henry; Kanhai, Humphrey H.H.; Brand, Anneke

doi:10.1111/j.1365-2249.2004.02496.x

Cited by 19 publications

(12 citation statements)

References 57 publications

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“…In addition, HPA‐1a antibodies might have an effect on endothelial cells αVβ3. Although CamTran007 does not lead to endothelial cell activation in a static in vitro system, 33 it does inhibit binding of transfectant cells expressing αVβ3 Leu‐33 to fibrinogen 28 . Results from studies that assess the effect on the interaction between endothelial cells, granulocytes, and PLTs in flowing blood are still lacking.…”

Section: Discussionmentioning

confidence: 99%

Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia

et al. 2007

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“…This improved neonatal course is likely to be, in part, the result Another main factor is, obviously, awareness of the diagnosis, with the opportunity to have matched platelets ready at delivery. In addition, we have to stress that IVIG likely acts in multiple ways in the prevention of ICH, such as through not yet completely clear protective effects on the endothelium [23]. More insight in these mechanisms is needed to determine the optimal use of IVIG in the antenatal and postnatal prevention of ICH.…”

Section: Discussionmentioning

confidence: 99%

Postnatal management of fetal and neonatal alloimmune thrombocytopenia: the role of matched platelet transfusion and IVIG

et al. 2006

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We evaluated the effects of platelet transfusions and intravenous immunoglobulin (IVIG) in neonates with fetal and neonatal alloimmune thrombocytopenia (FNAIT) with and without antenatal treatment with IVIG. Records of neonates with FNAIT admitted between January 2000 and November 2005 were reviewed. The patients were divided into group I, treated antenatally with IVIG for known FNAIT, and group II, postnatally diagnosed with FNAIT. The primary outcome was the time interval to reach a platelet level above 100 x 10(9)/L in relation to the type of treatment. Nineteen neonates with FNAIT were identified, 13 in group I and 6 in group II. In group I, four children were born with a platelet count above 100 x 10(9)/L and never needed treatment, and four received a single matched platelet transfusion at birth with a maintained response. Five neonates received IVIG and one matched transfusion, with all but one rapidly responding. In antenatally treated cases, postnatal IVIG had no apparent effect on the platelet count. In group II, two neonates died on day 1 with severe intracranial hemorrhage. Two of the four other patients responded to a number of unmatched platelet transfusions, with one neonate rapidly responding after one matched transfusion, while another needed nine matched transfusions before a persistent adequate platelet count was reached after 9 weeks. Postnatal IVIG had no apparent effect on the platelet count in any of our cases. In neonates with FNAIT treated antenatally with IVIG, neonatal management using a single matched platelet transfusion was adequate in all cases. In neonatally diagnosed cases not treated before birth, multiple matched platelet transfusions may be required. We found no evidence to support the use of IVIG in neonates with FNAIT.

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“…In terms of safety, we have already shown that the B2 series of antibodies have no significant adverse effects on platelet activation and function (50). HPA-1a antibodies also bind to endothelial cells αvβ3, but there is published evidence that B2G1 does not alter endothelial cell growth and activation status (51). Moreover, we have shown that ligand binding to αvβ3 is unaffected in the presence of B2G1 (C. Ghevaert, unpublished observations).…”

Section: Figurementioning

confidence: 92%

Developing recombinant HPA-1a–specific antibodies with abrogated Fcγ receptor binding for the treatment of fetomaternal alloimmune thrombocytopenia

Ghevaert

Wilcox²,

Fang³

et al. 2008

J. Clin. Invest.

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Fetomaternal alloimmune thrombocytopenia (FMAIT) is caused by maternal generation of antibodies specific for paternal platelet antigens and can lead to fetal intracranial hemorrhage. A SNP in the gene encoding integrin β3 causes a clinically important maternal-paternal antigenic difference; Leu33 generates the human platelet antigen 1a (HPA-1a), whereas Pro33 generates HPA-1b. As a potential treatment to prevent fetal intracranial hemorrhage in HPA-1a alloimmunized pregnancies, we generated an antibody that blocks the binding of maternal HPA-1a-specific antibodies to fetal HPA-1a1b platelets by combining a high-affinity human HPA-1a-specific scFv (B2) with an IgG1 constant region modified to minimize Fcγ receptor-dependent platelet destruction (G1Δnab). B2G1Δnab saturated HPA-1a + platelets and substantially inhibited binding of clinical HPA-1a-specific sera to HPA-1a + platelets. The response of monocytes to B2G1Δnab-sensitized platelets was substantially less than their response to unmodified B2G1, as measured by chemiluminescence. In addition, B2G1Δnab inhibited chemiluminescence induced by B2G1 and HPA-1a-specific sera. In a chimeric mouse model, B2G1 and polyclonal Ig preparations from clinical HPA-1a-specific sera reduced circulating HPA-1a + platelets, concomitant with transient thrombocytopenia. As the Δnab constant region is uninformative in mice, F(ab′) 2 B2G1 was used as a proof of principle blocking antibody and prevented the in vivo platelet destruction seen with B2G1 and polyclonal HPA-1a-specific antibodies. These results provide rationale for human clinical studies.

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Effect of maternal anti-HPA-1a antibodies and polyclonal IVIG on the activation status of vascular endothelial cells

Cited by 19 publications

References 57 publications

Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia

Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia

Postnatal management of fetal and neonatal alloimmune thrombocytopenia: the role of matched platelet transfusion and IVIG

Developing recombinant HPA-1a–specific antibodies with abrogated Fcγ receptor binding for the treatment of fetomaternal alloimmune thrombocytopenia

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