Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Background: Concomitant C4d and C3d detection in heart biopsies correlates with circulating DSA and graft dysfunction. Detection of C4d only in surveillance biopsies is not associated with graft dysfunction in majority of cases. However, conversion from C4d+ to C4d+/C3d+ is observed in 20% of cases (C4d converters). It was recently reported that IgM de novo DSA (dnDSA) was detectable before/at time of IgG dnDSA appearance for the same specificity. In addition DQ dnDSA was reported to be most prevalent posttransplantation and associated with poor outcomes. We tested the hypothesis that IgM dnDSA class switch to IgG dnDSA &/or development of DQ dnDSA are associated with progression of C4d+ to C4d+/C3d+.
Methods: Of 1589 transplants, 610 were screened for AMR between 2006-2012. We included patients with stored serum specimens collected ±1 day of initial biopsy and ≥ subsequent serum samples. Three groups were investigated including asymptomatic patients with C4d+ biopsies till last follow up (n=29), symptomatic patients with C4d+C3d+ biopsy (n=28) and patients who started as C4d+ then converted to C4d+C3d+ (n=11). We also compared other HLA antibody characteristics including presence of dnDSA, class I vs. class II, mean CPRA, MFI (of highest reacting DSA), C1q and serum 1:8 dilution testing results.
Results: C4d converters tended to have higher incidence of IgM DSA compared to C4d+ only (59 vs 82%, ns). Interestingly 5 converters had IgM DSA prior to detection of IgG DSA to the same specificity. Four of those showed IgG switch on a subsequent serum sample. Contrarily, of 10 C4d+ only patients who showed IgM DSA prior to detection of IgG DSA, only 1 patient switched to IgG (C4d+ vs. converters: 10% vs. 80%, p 0.017). C4d+ converters also had significantly higher incidence of DSA, predominantly DQ (91 vs 45%, p 0.01). There was no evidence that other DSA characteristics such as C1q results, MFI or serum dilution were associated with C4d conversion.
Conclusion: With the limitation of relatively small number of cases, our results demonstrate that both IgM dnDSA class switch to IgG and development of DQ dnDSA are significantly associated with increased risk of C4d conversion and progression of subclinical AMR and warrants further investigation in larger cohorts.
To cite this abstract in AMA style:Askar M, Rodriguez R, Klingman L, Thomas D, Zhang A, Morf H, Hamon N, Moazami N, Hsich E, Taylor D, Starling R, Tan C. Does Switching Predict Conversion: IgM De Novo Donor Specific HLA Antibodies Class Switch to IgG in Subclinical Antibody Mediated Rejection in Heart Transplant Recipients [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/does-switching-predict-conversion-igm-de-novo-donor-specific-hla-antibodies-class-switch-to-igg-in-subclinical-antibody-mediated-rejection-in-heart-transplant-recipients/. Accessed August 10, 2020.
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