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Improving the Predictive Value of the Virtual Crossmatch: Is the C1Q Assay Needed?

A. Colovai,1 C. Savchik,1 P. Masiakos,1 S. Calp-Inal,2 L. Kayler,3 E. Akalin.2

1Transplant Immunology Laboratory, Montefiore Medical Center, Bronx, NY
2Nephrology, Montefiore Medical Center, Bronx, NY
3Surgery, Montefiore Medical Center, Bronx, NY.

Meeting: 2015 American Transplant Congress

Abstract number: B242

Keywords: Histocompatibility, HLA antibodies, Kidney transplantation

Session Information

Session Name: Poster Session B: Translational Genetics and Proteomics in Transplantation

Session Type: Poster Session

Date: Sunday, May 3, 2015

Session Time: 5:30pm-6:30pm

 Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

The criteria for reporting unacceptable HLA antigens of renal transplant candidates differ greatly between transplant centers. In the attempt to refine these criteria, the experience of each center is valuable. In this study, we investigated whether pre-transplant screening of complement binding HLA antibodies using the C1q assay may improve the identification of unacceptable HLA antigens and the predictive value of the virtual crossmatch.

From Jan 1st 2011 to Sept 1st 2013, 296 patients received renal transplantation at our center. Anti-HLA antibodies were tested prior to transplantation using conventional (IgG) Mixed and Single Antigen Bead assays (One Lambda). Targets of HLA-A, -B, and -DR (MFI>5,000) and HLA-C and -DQ (MFI>10,000) antibodies were listed as unacceptable antigens in UNET. Thus, donor offers to patients with strong DSA were precluded. In patients who received offers, we accurately predicted negative/weak positive flow crossmatch (XM) and negative complement dependent cytotoxicity (CDC) XM results (p<0.0001). C1q binding capacity of pre-transplant DSA was tested retrospectively. Fifty-nine out of 60 patients with pre-formed DSA had no C1q binding DSA (98%). In only one patient, a DSA directed to DQ9 (DQB1*03:03/DQA1*02:01; MFI<3000) showed strong C1q reactivity (MFI>10,000). However, this antibody did not cause a positive crossmatch and its reactivity after DTT treatment was consistent with that of an IgM antibody.

Table 1. Virtual and Actual Crossmatch Results in 296 Renal Allograft Recipients
Patient Groups Low level DSA C1q+ DSA Flow crossmatch CDC Crossmatch Induction Therapy
N=236 Absent Absent Negative N/A Simulect/Thymo
N=44 Present Absent 43/44 Present 1/44 Negative N/A Thymo/IVIG
N=16 Present Absent Weak positive* Negative Thymo/IVIG
* Channel shift <150 for T cell XM; <250 for B cell XM.

These results indicate that testing the C1q binding capacity of pre-transplant DSA did not significantly change the stratification of immunological risk in our patients. Thus, the use of the C1q assay is dispensable in the assignment of unacceptable HLA antigens. Using well calibrated MFI cutoff values ensures a high predictive value of the virtual crossmatch in deceased donor renal transplant candidates.

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To cite this abstract in AMA style:

Colovai A, Savchik C, Masiakos P, Calp-Inal S, Kayler L, Akalin E. Improving the Predictive Value of the Virtual Crossmatch: Is the C1Q Assay Needed? [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/improving-the-predictive-value-of-the-virtual-crossmatch-is-the-c1q-assay-needed/. Accessed May 16, 2025.

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