Donor specific anti-HLA antibodies (DSA) are a major cause of antibody-mediated rejection (AMR) in transplantation. We investigated the specific roles of de novo anti-HLA DSA in AMR in renal and cardiac transplant patients. In this study we utilized several solid phase assays to detect the presence of anti-HLA DSA, and correlated the quantity of each antibody, classes of each, and capacity to bind and activate complement with histopathologic features found in biopsy studies. Among the 480 transplants performed between 2009 and 2014, we enrolled 17 renal and 36 cardiac patients with clinical and histopathologic diagnosis of AMR. We assessed de novo DSA MFI values as determined by LABScreen™ (OneLambda®), IgM, IgA, IgG1, IgG2, IgG3, IgG4, C1q, C1q+AHG, and C3d at the time of rejection. Overall, the C1q and C3d anti-HLA DSA profiles in the renal cohort yielded 100% PPV of AMR (C1q p<0.009; C3d p<0.003). IgG1 subclass anti-HLA DSA profiles correlated anti-HLA Class II DSA and tubulointerstitium damage in the transplanted grafts (p=0.05). In the cardiac cohort, the IgG3 anti- HLA DSA revealed a 100% PPV of AMR (p<0.05). Notable is that for renal transplantation anti-HLA Class II DSA correlated with rejection and the injury was primarily tubulointerstitial, consistent with the region where constitutive expression of HLA Class II occurs in renal tissue. Finding that detection of anti-HLA DSA by C1q, C3d, IgG1, and IgG3 anti-HLA assays correlates with histological characteristics of AMR in renal and cardiac allografts, indicates that monitoring for anti-HLA DSA by these assays may be used to detect patients at risk for AMR, and thus allow for earlier detection and treatment prior to graft injury or graft loss.
|Advisor:||Harville, Terry O.|
|Commitee:||Abul-Ezz, Sameh, Bellamy, William, Borja-Cacho, Daniel, Pandey, Soumya|
|School:||University of Arkansas for Medical Sciences|
|Department:||Interdisciplinary Biomedical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 77/09(E), Dissertation Abstracts International|
|Subjects:||Health sciences, Immunology|
|Keywords:||Anti-hla antibodies, Antibody mediated rejection, De novo antibodies, Donor specific antibodies, Tubulointerstitium damage|
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