Intravenous immunoglobulin–induced panel reactive antibody A reduction: not all preparations are created equal

Clark, Brendan; Cole, June Y.; Wortley, Alison; Toolan, John; Stoves, John; Newstead, Charles G.; Gooi, H. C.

doi:10.1097/01.tp.0000041723.19096.7a

Cited by 7 publications

(3 citation statements)

References 8 publications

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“…Multiple methods do exist to medically manage these patients in an attempt to decrease their level of circulating HLA antibodies and thereby hopefully decrease the risk of hyperacute as well as chronic rejection. A number of pre‐transplant strategies aimed at reducing the levels of circulating antibodies have been used with variable results including the administration of IVIG, plasmapheresis and the use of immunosuppressive medications including cyclophosphamide or mycophenolate mofetil (3, 7, 8). As a result of the increased risks, many centers will routinely require a mandatory prospective XM for those patients with PRA values >10% (4).…”

Section: Discussionmentioning

confidence: 99%

The virtual crossmatch – A screening tool for sensitized pediatric heart transplant recipients

Zangwill

Ellis

Zlotocha

et al. 2005

Pediatric Transplantation

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Heart transplantation in the setting of human leukocyte antigen (HLA) sensitization is challenging, as a time-consuming prospective crossmatch (XM) may be required, severely limiting the number of potential donors. We evaluated a 'virtual XM', defining a positive virtual XM as the presence of recipient pre-formed anti-HLA antibodies to the prospective donor HLA type, and compared the virtual XM to a standard direct XM. Bead-based flow cytometric analysis was used to identify anti-HLA antibody (Ab) present in a child listed for heart transplantation. Using recipient serum, direct-flow cytometric T- and B-cell XM were run for potential donors against whose HLA type the recipient had specific antibodies (group 1, n = 7) and for potential donors with predicted compatible HLA types by virtual XM (group 2, n = 7). Results were expressed as median channel difference (MCD) between the control and recipient serum. A positive T-cell XM was defined as MCD > 50, whereas MCD > 100 constituted a positive B-cell result. The rate of T-cell reactivity was significantly less in group 2 than in group 1 (29% vs. 100%, p = 0.02); similarly, B-cell reactivity was also less for group 2 (14% vs. 100%, p = 0.005). The virtual XM was 100% sensitive in detecting positive flow cytometric XM results for T and B cells. Although only 72% specific in predicting a negative T-cell XM, and 86% specific for negative B-cell XM, the false negatives were weakly positive and would probably have been clinically acceptable. Currently, potentially suitable donor organs are often declined for lack of a prospective XM; these organs may ultimately be allocated to more distant recipients or perhaps not used at all. While further studies are needed, virtual XM has the potential to improve availability of organs for sensitized patients and improve the overall allocation process.

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Section: Discussionmentioning

confidence: 99%

The virtual crossmatch – A screening tool for sensitized pediatric heart transplant recipients

Zangwill

Ellis

Zlotocha

et al. 2005

Pediatric Transplantation

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“…There are no published head‐to‐head studies comparing the in vivo effects of different IgG preparations on human alloimmune responses. However, at least one group has shown significant differences between IgG preparations in their ability to reduce PRA (when added in vitro ) [4]. Interestingly, differences were also found between different batches of the same commercial product.…”

Section: High‐dose Igg Protocolmentioning

confidence: 99%

Transplantation across previously incompatible immunological barriers

Magee

2006

Transplant Int

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“…The polyclonality of the Abs in IVIg, or innate differences in the commercial preparations of IVIg [44], may account for the conflicting reports and doubts on its reliability. Therefore, an ideal therapeutic agent to achieve the combinatorial effect of depleting T and B cells and upregulating Treg could be a well-defined monoclonal Ab (mAb), which not only enables better understanding of its modus operandi but would also be the most cost-effective therapeutic agent than the high-dose IVIg.…”

Section: Introductionmentioning

confidence: 99%

HLA Class Ia and Ib Polyreactive Anti-HLA-E IgG2a Monoclonal Antibodies (TFL-006 and TFL-007) Suppress Anti-HLA IgG Production by CD19+ B Cells and Proliferation of CD4+ T Cells While Upregulating Tregs

Ravindranath

2017

Journal of Immunology Research

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The anti-HLA-E IgG2a mAbs, TFL-006 and TFL-007, reacted with all HLA-I antigens, similar to the therapeutic preparations of IVIg. Indeed, IVIg lost its HLA reactivity, when its HLA-E reactivity was adsorbed out. US-FDA approved IVIg to reduce antibodies in autoimmune diseases. But the mechanism underlying IVIg-mediated antibody reduction could not be ascertained due to the presence of other polyclonal antibodies. In spite of it, the cost prohibitive high or low IVIg is administered to patients waiting for donor organ and for allograft recipients for lowering antiallograft antibodies. A mAb that could mimic IVIg in lowering Abs, with defined mechanism of action, would be highly beneficial for patients. Demonstrably, the anti-HLA-E mAbs mimicked several functions of IVIg relevant to suppressing the antiallograft Abs. The mAbs suppressed activated T cells and anti-HLA antibody production by activated B cells, which were dose-wise superior to IVIg. The anti-HLA-E mAb expanded CD4+, CD25+, and Foxp3+ Tregs, which are known to suppress T and B cells involved in antibody production. These defined functions of the anti-HLA-E IgG2a mAbs at a level superior to IVIg encourage developing their humanized version to lower antibodies in allograft recipients, to promote graft survival, and to control autoimmune diseases.

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Intravenous immunoglobulin–induced panel reactive antibody A reduction: not all preparations are created equal

Cited by 7 publications

References 8 publications

The virtual crossmatch – A screening tool for sensitized pediatric heart transplant recipients

The virtual crossmatch – A screening tool for sensitized pediatric heart transplant recipients

Transplantation across previously incompatible immunological barriers

HLA Class Ia and Ib Polyreactive Anti-HLA-E IgG2a Monoclonal Antibodies (TFL-006 and TFL-007) Suppress Anti-HLA IgG Production by CD19+ B Cells and Proliferation of CD4+ T Cells While Upregulating Tregs

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