Abstract 14016: The Development of De Novo Anti-hla Antibodies after Heart Transplant is Related to the Development of Rejection Depending of Their Complement Fixing Capability
Purpose: The development of anti-HLA donor specific antibodies (DSAs) after cardiac transplantation has been linked to rejection with mixed results. Our aim is to define whether de novo DSAs are associated with the development of antibody mediated rejection (AMR) or acute cellular rejection (ACR), and to determine if complement fixing capability of the DSAs influences this association.
Methods: De novo development of DSAs was assayed quarterly in 132 consecutive patients following heart transplantation, between January 2006 and July 2011. A new analytical method developed at our institution was used to differentiate DSAs capable of fixing the first component of the complement cascade (IgG+/C1q +) from non-complement fixing antibodies (IgG+/ C1q-). The frequency of either class of DSA was compared in patients with ACR, defined as a biopsy grade 3A/2R or higher using the ISHLT classification system; and in AMR, defined as a positive biopsy staining for C4d, C3d or CD68.
Results: 20 patients with DSAs prior to transplantation were excluded from analysis. Among the 112 patients studied (mean age 49 years-min19, max 72-, 71% males), 80 (71.4%) patients did not develop any DSA during follow-up, 16 (14.3%) developed IgG+/c1q- DSAs and 16 patients (14.3%) developed IgG+/c1q+ DSA. Overall, patients with de novo DSAs experienced rejection more frequently than patients without DSAs, both ACR (47% vs. 20%, OR 4.0, p<0.001) and AMR (31.2% vs. 6%, OR 6.8, p=0.001). Patients with IgG+/C1q- DSAs more frequently experienced ACR (68% vs. 20%, HR 8.8, p<0.001), but no AMR. In contrast, patients with IgG+/C1q+ DSAs showed no predisposition to ACR (27% vs. 20%, HR 1.8, p=0.332), but had a higher odds of AMR (43.7% vs. 6%, HR 11.6, p<0.001.
Conclusion: The development of de novo DSAs after heart transplantation was clearly associated with the presence of both AMR and ACR in our population. IgG+/c1q- DSAs were associated only with ACR, and IgG+/C1q + DSAs showed a strong relationship with AMR only. These results suggest the importance of monitoring DSAs post-transplant. Early detection of IgG+/C1q+ DSAs can specifically identify a subgroup of patients at risk of AMR who could potentially benefit from preventive therapies.
- © 2012 by American Heart Association, Inc.