OR4 A case of heart valve replacement leading to extensive sensitization

Abstract

HLA antibody (Ab) sensitization is a major barrier to transplantation. We present a case of a 9 year old girl who was assessed for heart–lung transplantation due to left ventricular outflow tract obstruction and pulmonary venous hypertension. Assessment with single antigen bead (SAB) testing for HLA Ab revealed a cPRA = 100%; the key sensitizing event was an aortic heart valve homograft 6 months prior. The patient was also transfused and had been on ECMO. The patient was unsensitized prior to the homograft and suffered a S. pneumonae infection that may have contributed to sensitization. Patient and homograft donor were HLA typed at all loci including DQA1,DPA1, and DPB1. Only HLA-C was matched, with all other loci fully mismatched except for 1/2 for DPA1 and DPB1. The degree of sensitization was high for both class I and II HLA–cPRA = 100% for each (Canadian cPRA) calculated for Abs with an MFI > 1000. Epitope spreading was evident with SAB testing for total IgG. When assessed for C1Q-binding IgG, the only Abs detected were to mismatched homograft antigens and closely related antigens, which still produced a cPRA = 96% (Table 1). Much of the sensitization was due to the patient’s HLA type which lacked public class I epitopes; Aw4, and class II; DR51/52/53, as well as DQ1 and DQ3, related to being homozygous for least common class II HLA types as described in Fig. 1. The patient is currently on the waitlist and is unlikely to find a compatible donor. This case highlights the significant impact of HLA mismatches in homograft implants, particularly in patients with unique HLA types. It also provides insight into the properties of HLA Abs formed in the absence of immunosuppression, as evidenced by the differences in SAB testing for total IgG versus C1Q-binding IgG. Download : Download full-size image Download : Download full-size image L. Hidalgo: Speaker’s Bureau; Company/Organization; Thermo Fisher (One Lambda).