Background
Kidney transplantation (KT) between donors and recipients with HIV is promising. However, allograft rejection risk among recipients with HIV (R+) is higher than recipients without HIV (R-). This study evaluated predictive antibody markers of KT allograft rejection among R+.
Methods
The HOPE in Action Multicenter Kidney Trial performed KT in R+ between 2018-2021 from donors with HIV (D+) and without HIV (D-) and followed KT R+ for adverse events and survival. Targets of plasma antibody reactivity in donors and recipients were quantified using phage immunoprecipitation sequencing (PhIP-Seq). Antibody targets with 5%-95% reactivity were included: 4667 viral peptides and 130 viral species, 667 toxin peptides, and 1427 human peptides. We used continuous Viral Aggregate Reactivity score (VARscore) to integrate the intensity and breadth of response to all antibody peptides for each viral species. Fisher’s exact tests and wilcoxon rank sum tests were used to evaluate the association between pre-KT antibodylevels and rejection after KT. We used the Bonferroni method to correct multiple comparisons. Analyses were additionally stratified by sex.
Results
There were 64 D+ and 82 D-, and 198 R+ (99 D+/R+ and 99 D-/R+). Most donors (69%) and R+ (82%) were male. Seven female and 31 male R+ had either antibody or cellular mediated rejection after KT. The median total hits of human peptides was higher in D+ (127 [IQR=103-144]) than D- (111 [IQR=78-130]) (p=0.006). Donor HIV status was associated with reactivity to cytomegalovirus, Epstein-Barr virus, and herpesvirus antibody peptides (p<0.05). Among D+ and D-, pre-KT antibody peptides of viruses (adenoviruses and cytomegalovirus), toxins (Mycoplasma pneumoniae), and human (glucocorticoid receptor isoform gamma, and melanophilin isoform 1) were associated with rejection in R+ (p<0.05), but the association was not significant after adjusting for multiple comparisons. The median VarScore of Adenovirus A12 was significantly higher among donors whose R+ had rejection, than donors whose R+ did not have rejection (p=3.7×10-5) (Figure). Donors’ HIV viral antibodies were not associated with rejection in R+ (p>0.05). Sex stratified analysis gave similar but non-significant results with smaller sample size.
Conclusions
Reactivity of donor HIV antibodies was not associated with rejection among R+, adding the evidence of the safety of D+/R+ KT. However, pre-KT adenoviruses infection for both donors and recipients might require special attention.
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