RELEVANCE OF DRw52-SPECIFIC ANTIBODY IN RENAL TRANSPLANTATION.
K Schillinger, M Samaniego, LC Racusen, M Paparounis, MS Leffell, AA Zachary, Depts. of Medicine, Nephrology, and Pathology, Johns Hopkins U., Baltimore, MD

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Antibodies specific for donor HLA-DR (DRB1) or HLA-DQ have been shown to result in hyperacute or acute humoral rejection of renal grafts. However, the effect of antibodies specific for molecules encoded by other HLA-DRB loci (3-5), which are expressed at lower levels than is DRB1, is not known. We report here, the case of a patient with antibody specific for the donor=s DRw52 antigen but a negative cytotoxicity (CYT) B cell crossmatch at the time of renal transplantation. Despite an ongoing increase in the level of DRw52-specific antibody, the patient showed no overt signs of rejection for 23 months following transplantation. At 23 months (T+23) post-transplant, the patient underwent surgery for goiter. Ten days after surgery, the serum creatinine had increased from 1.4 to 1.8mg/dl and Tx biopsy revealed many inflammatory cells marginating in glomerular and peritubular capillaries along with focal linear staining for C3d and C4d. These findings are consistent with Ab-mediated rejection. Between T+11 and T+24, there was an increase in antibody titer and in the proportion of antibody that was IgG vs. IgM. Absorption studies have confirmed the specificity of the antibody to be DRw52. ELISA, flow cytometric, and cytotoxicity assays confirmed the absence of antibody to donor class I antigens. We believe these data suggest that the DRw52-specific antibody did not produce overt clinical symptoms because the constitutive expression is 15-20% the level of that of DRB1 products. The appearance of clinical symptoms following surgery could have resulted from a trauma-induced release of cytokines and/or hormonal changes that upregulated HLA expression. It is possible that antibodies to HLA antigens with low constitutive expression may contribute to a subclinical and potentially progressive or Achronic-like@ rejection in the absence of increased expression of the target molecules.