P127 : TO TRANSPLANT OR NOT TO TRANSPLANT ACROSS A STRONGLY POSITIVE CROSSMATCH?

Abstract

To evaluate the clinical significance of a strongly positive crossmatch in a highly sensitized end stage renal disease patient with Anti-Neutrophil Cytoplasmic Antibody (ANCA) positive Wegener’s Syndrome. The patient was evaluated for the presence and specificity of HLA antibodies by flow cytometry and microarray. Crossmatches were performed by lymphocytoxicity (cyto) and by flow cytometry. FCXM used both untreated and pronase treated T and B cells. A standard anti-nuclear antibody (ANA) panel was performed by microarray and ANCA was performed by immunofluorescence. The patient was found to be highly sensitized to multiple Class I and II HLA antigens, with a 100% Calculated Percent Reactive Antibody. A virtual crossmatch with a 0 ABDR mismatched deceased donor was predicted to be negative, but the prospective crossmatch gave unexpected results. The T and B cell cyto and standard FCXM results were strongly positive while the pronase FCXM was negative. The standard autologous FCXM was negative. The patient’s antibody reacted to a titer of 1:32 in a surrogate donor cyto XM. The ANA panel was negative. The ANCA test was positive at a titer of 1:160 with a cytoplasmic staining pattern. However, both the more typical C-ANCA Proteinase 3 (PR3) and P-ANCA Myeloperoxidase (MPO) antibodies were negative. Given, the unknown clinical significance of the crossmatch reactivity, the patient was transplanted following a 2 volume plasma exchange and IVIg 500 mg/kg which reduced the antibody to undetectable levels by cyto. While antibody levels rebounded post-transplant, the graft is functioning well 12 days post-transplant. The crossmatch results implicate antibody against a non-HLA, pronase-sensitive antigen. This patient’s ANCA lacks the typical PR3 and MPO specificities, and suggest the ANCA target antigen is atypical. Atypical ANCA directed against a target antigen expressed on T and B cells may be responsible for the positive crossmatches. Anti-LAMP2 (CD106) is a possible candidate in that it is believed to be present in a high number of patients with active ANCA disease. Several amino acid sequences on the CD106 structure are predicted pronase cleavage sites. Both renal tissue and lymphocytes are known to express LAMP2. Additional studies are necessary to identify the target antigen.