Intravenous (IV) anti‐D and IV immunoglobulin achieve acute platelet increases by different mechanisms: modulation of cytokine and platelet responses to IV anti‐D by Fc<i>γ</i>RIIa and Fc<i>γ</i>RIIIa polymorphisms

Cooper, Nichola; Heddle, Nancy M.; Haas, Masja de; Reid, Marion E.; Lesser, Martin; Fleit, Howard B.; Woloski, B.M.R.N.J.; Bussel, James B.

doi:10.1111/j.1365-2141.2004.04804.x

Cited by 89 publications

(80 citation statements)

References 43 publications

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“…These agents may inhibit the FcR-mediated clearance by different mechanisms [23]. IVIG in humanized mouse models has been shown to have its primary effect by upregulating FcRIIb, whereas anti-D is thought to interact primarily with FcRIIa and FcRIIIa [24].…”

Section: Discussionmentioning

confidence: 99%

Superior effect of intravenous anti‐D compared with IV gammaglobulin in the treatment of HIV‐thrombocytopenia: Results of a small, randomized prospective comparison

Scaradavou

Cunningham‐Rundles

et al. 2006

American J Hematol

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This small, prospective, randomized study compared increases in platelet counts and duration of response after intravenous gammaglobulin (IVIG) and IV anti-D in patients with HIVrelated thrombocytopenia (HIV-TP). Nine Rh+, nonsplenectomized HIV-positive patients with thrombocytopenia were treated sequentially, in random order, with IVIG and IV anti-D in a cross over design, receiving each therapy for 3 months. Peak platelet counts and duration of effect after each treatment were compared. In addition, viral load measurements and CD4 counts were followed serially, as well as thrombopoietin levels. IV anti-D resulted in a mean peak platelet count of 77 x 10 9 /L compared to only 29 x 10 9 /L after IVIG (P = 0.07). The mean duration of response was significantly longer in patients treated with anti-D (41 days) compared to IVIG (19 days, P ¼ 0.01). No consistent changes were seen in the CD4 counts or viral load measurements as a result of either therapy. Thrombopoietin levels were normal in all patients despite often severe thrombocytopenia. Anti-D was more efficacious than IVIG for the treatment of HIV-TP, confirming and extending previous results. Anti-D should be the first line therapy in HIV-positive, Rh+ patients, when antiretroviral agents are not indicated, not effective, or there is an urgent need to increase the platelet count. Am. J. Hematol. 82:335-341, 2007. V V C 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Superior effect of intravenous anti‐D compared with IV gammaglobulin in the treatment of HIV‐thrombocytopenia: Results of a small, randomized prospective comparison

Scaradavou

Cunningham‐Rundles

et al. 2006

American J Hematol

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“…Multiple mechanisms for IVIG and anti-RBC action in ITP have been proposed, 8,[25][26][27][28][29] and the exact mechanisms of action of anti-RBC antibody, IVIG, and antibody-coated liposomes are not clear and will be a focus of future work in this laboratory. Recently, Siragam et al 30 suggested that IVIG and anti-RBC antibody achieve effects via different mechanisms, either through effects of small, soluble immune complexes on Fc␥RIIB (eg, IVIG) or through effects of large, particulate immune complexes on Fc␥RIII (eg, antibody-coated RBCs).…”

Section: Discussionmentioning

confidence: 99%

“…24 The present study clearly showed that IVIG altered the systemic exposure of MWReg30 (AUC 96-264h values decreased from 1795 nMϫh in the control group to 835 nMϫh in 2 g/kg IVIG treatment group; Figure 7), consistent with an effect of IVIG on MWReg30 elimination. The significance of the effect of IVIG on MWReg30 disposition has not yet been quantitatively evaluated; however, given the magnitude of the change in MWReg30 exposure, it is likely that IVIG-mediated increases in MWReg30 clearance contributes to the observed effects of IVIG on MWReg30-induced thrombocytopenia.Multiple mechanisms for IVIG and anti-RBC action in ITP have been proposed, 8,[25][26][27][28][29] and the exact mechanisms of action of anti-RBC antibody, IVIG, and antibody-coated liposomes are not clear and will be a focus of future work in this laboratory. Recently, Siragam et al 30 suggested that IVIG and anti-RBC antibody achieve effects via different mechanisms, either through effects of small, soluble immune complexes on Fc␥RIIB (eg, IVIG) or through effects of large, particulate immune complexes on Fc␥RIII (eg, antibody-coated RBCs).…”

mentioning

confidence: 99%

Comparison of the effects of antibody-coated liposomes, IVIG, and anti-RBC immunotherapy in a murine model of passive chronic immune thrombocytopenia

Deng

Balthasar

2006

Blood

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IntroductionImmune thrombocytopenia (ITP) is classified as an autoimmune disease in which antibody-coated platelets are phagocytosed by macrophages in the reticuloendothelial system (RES) through Fc␥ receptor-mediated or complement-mediated pathways. 1 There are about 33 000 new cases of ITP diagnosed in the United States each year. [2][3][4] Platelets play an important role in blood homeostasis and vascular repair; consequently, thrombocytopenic patients are at risk for the development of purpura, petechiae, or even life-threatening bleeding such as intracranial hemorrhage. Corticosteroids, splenectomy, intravenous immunoglobulin (IVIG), anti-D immunotherapy, and plasmapheresis have been used to acutely increase platelet counts in the treatment of ITP. 2-4 However, the above therapies are associated with troubling side effects and high cost. In addition, some ITP patients do not respond to any of the existing therapies; therefore, there is substantial need for the development of new strategies to treat this disease.In 1981, Imbach et al 5 reported the therapeutic efficacy of high-dose IVIG in ITP patients. Later, Salama et al 6 proposed that IVIG contained anti-red blood cell (anti-RBC) antibodies, which led to the opsonization of RBCs in vivo following IVIG administration. Additionally, Salama et al 6 hypothesized that antibodyopsonized RBCs competed for binding to Fc␥ receptors, effectively inhibiting the Fc␥ receptor-mediated elimination of platelets in ITP patients. Consistent with this hypothesis, anti-D, a polyclonal antibody preparation against the D antigens on the RBC, has been used to treat Rh ϩ ITP successfully. 2,7,8 Although anti-D has been Food and Drug Administration (FDA)-approved to treat ITP, this therapy is rarely associated with intravascular hemolysis, leading to severe anemia and, in very rare cases, death. 9,10 Additionally, anti-D has not demonstrated efficacy in D-negative patients or in splenectomized patients. 7,8 We have proposed that antibody-coated liposomes may be used in place of anti-D to compete for pathways for platelet elimination in ITP. 11 Previous work has shown that antibody-coated liposomes increased platelet counts in a rat model of acute passive ITP. 11 A murine model of chronic passive ITP, which may be more similar to human ITP, was developed here. The effects of antibody-coated liposomes were examined and compared with effects observed following treatment with IVIG or treatment with an anti-RBC monoclonal antibody (TER119). Our data showed that antibodycoated liposomes, IVIG, and TER119 increased platelet counts in this model. Antibody-coated liposomes achieved effects at a much lower immunoglobulin dose than that required for IVIG and, in contrast with TER119, antibody-coated liposomes achieved an increase in platelet counts without altering RBC counts. Materials and methods MiceFemale Balb/c mice (20 g) were obtained from Harlan (Bar Harbor, ME). Mice were kept under a natural light/dark cycle, maintained at 22 Ϯ 4°C, and fed with standard diet and water ad libitu...

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“…This down modulation in FcgRIII was not observed with another donor-derived immunoglobulin used to treat ITP (intravenous immunoglobulin; IVIg) indicating that the mechanisms of the two donor-derived polyclonal therapeutics were likely fundamentally different [11]. In human patients receiving anti-D, Cooper also showed that the spectrum of cytokines produced in patients receiving anti-D versus IVIg were different [13]. Today, we do not as yet have a confirmed mechanism of action for polyclonal anti-D (nor IVIg) and thus the successful development of any particular monoclonal anti-D antibody for human patients with ITP could be considered a risky venture.…”

Section: Polyclonal Versus Monoclonal Anti-dmentioning

confidence: 85%

Monoclonal versus polyclonal anti-D in the treatment of ITP

Lazarus

2013

Expert Opinion on Biological Therapy

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Intravenous (IV) anti‐D and IV immunoglobulin achieve acute platelet increases by different mechanisms: modulation of cytokine and platelet responses to IV anti‐D by FcγRIIa and FcγRIIIa polymorphisms

Cited by 89 publications

References 43 publications

Superior effect of intravenous anti‐D compared with IV gammaglobulin in the treatment of HIV‐thrombocytopenia: Results of a small, randomized prospective comparison

Superior effect of intravenous anti‐D compared with IV gammaglobulin in the treatment of HIV‐thrombocytopenia: Results of a small, randomized prospective comparison

Comparison of the effects of antibody-coated liposomes, IVIG, and anti-RBC immunotherapy in a murine model of passive chronic immune thrombocytopenia

Monoclonal versus polyclonal anti-D in the treatment of ITP

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