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- W4251788181 abstract "Introduction: Donor specific antibodies (DSA) to mismatched HLA class II antigens remain a barrier to long term kidney graft survival. We investigated the relationship of de novo class II DSA generation calcineurin inhibitor (CNI) levels, and graft survival in kidney transplantation. Methods: Class II DSA and CNI (tacrolimus (TAC), cyclosporin (CS)) levels were compared in 472 kidney transplant recipients undergoing DSA testing post-transplant. Patients were subdivided into three groups according to CNI levels measured within the year prior to the time of DSA testing: Normal - TAC>4/ CS>75 (N=299), Low - TAC=3-4/ CS=50-75 (N=86), Very Low - TAC< 3/ CS< 50 (N=87). The incidence of DSA was calculated for each class II locus (HLA-DRB1, -DRB3/4/5, and -DQB1) as a percent of the times that locus was mismatched in each group. DSA to DRB1 in patients with Low or Very Low CNI levels were combined due to the low number of these antibodies in the Low CNI group. Results: As a percent of the number of mismatched antigens, the highest incidence of DSA in this patient population was against DQ7/8/9, followed by DQ2, DQ4, DQ5/6, DRB3/4/5, and DRB1 DSA (Figure 1). The highest incidence of DSA was observed in patients with very low CNI levels who developed DSA against DQ7/8/9 56.7% of the time these antigens were mismatched. The incidence of DQ7/8/9 and DQ4 DSA dramatically decreased with increasing CNI levels whereas DQ2 DSA and DQ5/6 DSA decreased modestly. The incidence of DSA to HLA-DR loci did not change with CNI levels.[FIGURE 1]We also examined the effect of DSA specificities on graft loss. The incidence of DSA to the class II loci indicated above was repeated but only including patients who had lost their grafts (N=103). Within this cohort the incidence of DSA was again highest for DQ7/8/9 DSA (61.8%), followed by DQ2, DQ5/6, DQ4, DRB1, and DRB3/4/5 (Table 1).[TABLE 1. DSA IN PATIENTS WITH GRAFT LOSS]Conclusion: Our data suggest that higher CNI levels may help decrease the incidence of class II DSA to certain mismatched loci and also lower the increased risk of graft loss. Further work may allow for target CNI levels to be customized for kidney transplant patients based on mismatched donor HLA class II antigens." @default.
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- W4251788181 date "2012-11-01" @default.
- W4251788181 modified "2023-10-14" @default.
- W4251788181 title "The Incidence of Class II DSA According to Mismatched Alleles Is Affected by Calcineurin Inhibitor Drug Levels" @default.
- W4251788181 doi "https://doi.org/10.1097/00007890-201211271-01548" @default.
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