Using real data for a virtual crossmatch

Zachary, Andrea A.; Sholander, Jeffrey T.; Houp, Julie A.; Leffell, Mary S.

doi:10.1016/j.humimm.2009.06.007

Cited by 129 publications

(108 citation statements)

References 24 publications

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“…Calculated panel reactive antibody was determined for antibodies sufficient to yield a positive cytotoxicity or FCXM using virtual crossmatch methods and the online UNOS CPRA calculator. 21 Non-HLA AECAs were detected using an FCXM performed using angiopoietin receptor positive (Tie-2+) peripheral blood ECPs 22 (XM-ONE; Absorber AB, Stockholm, Sweden) acquired on a BD FACSAria using FACSDiva (version 6.1.1; BD Biosciences, Franklin Lakes, NJ).…”

Section: Hla Antibody Detection and Crossmatch Testsmentioning

confidence: 99%

“…Shown are scores from all biopsies or a subset of biopsies when HLA-DSA was not detected at time of biopsy or detected at a negative FCXM level. 21 Histologic scoring (0-3) was performed using updated Banff 1997-2007 criteria. [27][28][29][30] Shown are grades for glomerulitis (g), interstitial (i) and tubular (t) inflammation, vasculitis (v), and peritubular capillaritis (ptc).…”

Section: Analyses After Endothelial Cell Culture Stimulationmentioning

confidence: 99%

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Endothelial Cell Antibodies Associated with Novel Targets and Increased Rejection

Jackson¹,

Sigdel

Delville

et al. 2015

Journal of the American Society of Nephrology

112

107

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The initial contact point between a recipient's immune system and a transplanted graft is the vascular endothelium. Clinical studies suggest a pathogenic role for non-HLA antiendothelial cell antibodies (AECAs) in allograft rejection; however, evidence linking AECAs of known specificity to in vivo vascular injury is lacking. Here, we used high-density protein arrays to identify target antigens for AECAs isolated from the sera of recipients of kidney transplants experiencing antibody-mediated rejection in the absence of donor-specific HLA antibodies. Four antigenic targets expressed on endothelial cells were identified: endoglin, Fms-like tyrosine kinase-3 ligand, EGF-like repeats and discoidin I-like domains 3, and intercellular adhesion molecule 4; the first three have been implicated in endothelial cell activation and leukocyte extravasation. To validate these findings, ELISAs were constructed, and sera from an additional 150 renal recipients were tested. All four AECAs were detected in 24% of pretransplant sera, and they were associated with post-transplant donorspecific HLA antibodies, antibody-mediated rejection, and early transplant glomerulopathy. AECA stimulation of endothelial cell cultures increased adhesion molecule expression and production of inflammatory cytokines: regulated on activation, normal T cell expressed and secreted PDGF and RESISTIN. These correlations between in vitro experiments and in vivo histopathology suggest that AECAs activate the vascular endothelium, amplifying the alloimmune response and increasing microvascular damage. Given the growing number of transplant candidates, a better understanding of the antigenic targets, beyond HLA, and mechanisms of immune injury will be essential for improving long-term allograft survival.

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Section: Hla Antibody Detection and Crossmatch Testsmentioning

confidence: 99%

Section: Analyses After Endothelial Cell Culture Stimulationmentioning

confidence: 99%

Endothelial Cell Antibodies Associated with Novel Targets and Increased Rejection

Jackson¹,

Sigdel

Delville

et al. 2015

Journal of the American Society of Nephrology

112

107

View full text Add to dashboard Cite

show abstract

“…However, it has been found that the treatment of serum with moderate heat, dilution, hypotonic dialysis, EDTA, or dithiothreitol abrogates the prozone effect. [18][19][20] By way of an example, serum can be pretreated for 10 minutes with a 0.1 M solution of pH 7.4 disodium EDTA diluted 1:10 prior to the SAFB assay. 12 The complement-dependent cytotoxicity crossmatch assay can be positive with immunoglobulin M only.…”

Section: False-negative Bead Assay Resultsmentioning

confidence: 99%

Untitled

Desoutter

Apithy²,

Guillaume³

2017

Exp Clin Transplant

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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.

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“…Nevertheless, several studies have shown that low antibody levels are not always associated with adverse effects. Therefore, clinically irrelevant anti-HLA antibody detection could lead to discrimination against some immunized patients at time of organ allocation, if clinically irrelevant antibodies are evaluated as assigning an unacceptable antigen in virtual compatibility crossmatch (VXM) [42]. VXM allows exclusion of donors who express HLA antigens against which a patient is immunized.…”

Section: Virtual and Luminex Crossmatchmentioning

confidence: 99%

Luminex and antibody detection in kidney transplantation

2012

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Preformed anti-human leukocyte antigen (HLA) antibodies have a negative effect on kidney transplantation outcome with an increased rejection rate and reduction in survival. Posttransplantation production of donor-specific anti-HLA antibodies is indicative of an active immune response and risk of transplantation rejection. For many years the primary technique for anti-HLA antibody detection was complement-dependent cytotoxicity (CDC), which has been integrated by solid-phase assays as HLA antigen-coated bead methods (Luminex). This new technological approach has allowed identification of anti-HLA antibodies, not detectable using conventional CDC method, in patients awaiting kidney transplantation. Moreover, use of Luminex technology has enabled better definition of acceptable or unacceptable antigens favoring transplantation in highly immunized patients. However, there are still many unresolved issues, including the clinical relevance of antibodies detected with this system.

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Using real data for a virtual crossmatch

Cited by 129 publications

References 24 publications

Endothelial Cell Antibodies Associated with Novel Targets and Increased Rejection

Endothelial Cell Antibodies Associated with Novel Targets and Increased Rejection

Untitled

Luminex and antibody detection in kidney transplantation

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