P127 Unexpected negative crossmatch in a patient with high level ANTI-HLA-DQA donor specific antibodies

Abstract

In 2014 OPTN/UNOS approved a policy to include DQA1 as part of the allocation process but the effect of preformed DQA donor specific antibody (DSA) on graft survival is not fully understood. We present a case of a negative flow cytometric crossmatch (FXCM) and good graft survival in a patient with preformed DQA DSA, suggesting that DQ expression affects the impact of these antibodies. A 43 year old male presented for renal re-transplant and evaluation by single antigen beads revealed antibodies against DQ 2 and DQA 4, 5, & 6 (Table 1). A virtual crossmatch (VXM) with a deceased donor was incompatible due anti-DQA 5 DSA at ∼ 23,000MFI. A FCXM was, surprisingly, compatible on three serum dates tested. DSA testing 24 h post-transplant revealed anti-DQA 5 at ∼ 20,000 MFI. C1q testing revealed anti-DQA 5 at ∼ 31,000MFI. Confirmatory typing and a repeat FCXM were consistent with initial testing. A surrogate FCXM with a DQA 5 donor was B-cell positive (502 MCS [cutoff 270 MCS]). At day 3, the patient had delayed graft function with creatinine of 14.3 mg/dL. However, a biopsy showed no evidence of rejection and C4d staining was negative. At day 49, the creatinine had decreased to 2.27 mg/dL and the biopsy remained negative. The patient continues to have good graft function two years post-transplant. DQ is differentially expressed primarily through the class II transactivator (CIITA) pathway. The CIITA-PIII promoter drives constitutive expression of CIITA in B cells and can be activated by IFN γ in non-B cells. Epigenetic changes in CIITA-PIII can result in complete abrogation of CIITA and, consequently, DQ expression. It is possible that downregulation of CIITA in this donor resulted in minimal DQ expression in the graft. Due to the incompatibility of the VXM this patient could have been denied the benefits of transplantation. Studies of DQ expression are limited in transplantation and should be an area of increasing investigation as the ability to identify acceptably mismatched organs continues to advance. Download : Download high-res image (147KB) Download : Download full-size image