New Crossmatch Technique Eliminates Interference by Humanized and Chimeric Monoclonal Antibodies

Book, Benita K.; Ágarwal, Avinash Kumar; Milgrom, Al; Bearden, Christopher M.; Sidner, Richard A.; Higgins, Nasra; Pescovitz, Mark D.

doi:10.1016/j.transproceed.2004.12.066

Cited by 37 publications

(28 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dosing dramatically impairs response to a neoantigen given at the time of rituximab dosing but ultimately has no effect on preexisting memory responses (56). Last, we reported methods to perform CMX and PRA determinations in patients who had been treated with rituximab either by elimination of the cell surface CD20 by pronase treatment of the cells or by immunomagnetic bead absorption of the serum-containing rituximab (57,58). In our small phase 1 study, we found that there was a decrease in PRA and or antibody specificity in most of the patients, data that were confirmed recently using single-antigen HLA beads (59).…”

Section: Other Approaches To Desensitizationmentioning

confidence: 99%

Presensitization

Jordan¹,

Pescovitz²

2006

Clinical Journal of the American Society of Nephrology

110

View full text Add to dashboard Cite

Much attention has been placed recently on transplantation in highly HLA-sensitized patients. In attempts to remove these antibodies and enable successful transplantation, several novel approaches have been developed. These include intravenous Ig (IVIg), mycophenolate mofetil, sirolimus, alemtuzumab, protein A immunoabsorption, and rituximab. IVIg has emerged as a very effective agent when used alone in high dose or when used in low dose and combined with plasmapheresis. Although alemtuzumab has been used to eliminated B cells, it fails to prevent antibody-mediated rejection and therefore probably is not suitable for desensitization. Rituximab, a B cell-specific antibody, seems to be safe and to have some efficacy as a sole agent in elimination of alloantibodies but most likely will require combination therapy with IVIg or other agents. Newer agents, such as humanized anti-CD20, are being developed. Despite the great interest in the problem of allosensitization, with one notable exception, there is a major deficiency in controlled clinical trials, the conduct of which should be a focus for the near future.

show abstract

Section: Other Approaches To Desensitizationmentioning

confidence: 99%

Presensitization

Jordan¹,

Pescovitz²

2006

Clinical Journal of the American Society of Nephrology

110

View full text Add to dashboard Cite

show abstract

“…25,26 Interference by therapeutic antibodies and other treatments The therapeutic antibodies used to treat acute rejection or to desensitize patients (such as rituximab [an anti-CD20 antibody], daclizumab [anti-CD25], and alemtuzumab [anti-CD52]) can interfere with crossmatching assays. 27 In a recent study, CDC-XM was performed after the addition of various concentrations of therapeutic antibodies (intravenous immunoglobulins, rituximab, basiliximab, eculizumab, and antithymocyte globulin) to negative and positive control sera. 28 Rituximab and antithymocyte globulin were respectively associated with false-positive B-cell CDC crossmatches and false-positive T-and B-cell CDC crossmatches.…”

Section: Human Immunodeficiency Virus-positive Casesmentioning

confidence: 99%

“…29 In the context of rituximab therapy, CDC-XM positivity is restricted to B cells. 30 False-positive CDC-XMs may be produced at low serum rituximab 27 Yes (a high dose of daclizumab Yes (T-and B-cells) No produces low-level interference for B-cells) Basiliximab (anti-CD25) 28 No No No Alemtuzumab (anti-CD52) 27 Yes (T-and B-cells) Yes (T-and B-cells) No Eculizumab (anti-C5) 28 No No No Antithymocyte globulin 28 …”

Section: Human Immunodeficiency Virus-positive Casesmentioning

confidence: 99%

Untitled

Desoutter

Apithy²,

Guillaume³

2017

Exp Clin Transplant

View full text Add to dashboard Cite

Preformed donor-specific antibodies against human leukocyte antigen can induce antibody-mediated rejection after organ transplant. Hence, future transplant recipients undergo pretransplant screening for preformed antibodies (ie, virtual crossmatch). Subsequently, prospective (analytic) crossmatching is performed using conventional, complementdependent cytotoxicity assays and/or flow cytometrybased methods. The present article reviews factors that must be considered when unexpected, positive, prospective crossmatches are observed. First, the prozone effect caused by the interference of complement or immunoglobulin M must be abrogated by treating the serum with moderate heat, dilution, hypotonic dialysis, EDTA, or dithiothreitol. Second, the physician must check for the presence of potentially interfering autoantibodies (in a context of autoimmune disease or human immunodeficiency virus infection) or therapeutic antibodies (such as rituximab and antithymocyte globulin). In conclusion, knowledge of each assay's technical characteristics will enable the physician to reliably interpret any discrepancies. The reasons for an unexpected, positive, prospective crossmatch must be elucidated before transplant to ensure efficient organ allocation and optimize patient outcomes.

show abstract

“…Other therapeutic monoclonal antibodies, such as Campath (anti-CD52), cannot be adsorbed from patient sera. In these circumstances, a crossmatch will always appear positive, although positive SPADS, including a recently developed immunosorbent crossmatch assay [59] will not be affected. It is critical that the laboratory be informed when patients have received any monoclonal or polyclonal antibody Fig.…”

Section: Confounding Issues: Post-transplantation Conundrums and Chalmentioning

confidence: 99%