Differential Impact of Class I and Class II Panel Reactive Antibodies on Post-Heart Transplant Outcomes

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ABSTRACT

Background

Sensitized patients awaiting heart transplantation spend a longer time on the waitlist and have higher mortality. We are now able to further characterize sensitization by discriminating antibodies against class I and II, but the differential impact of these has not been assessed systematically.

Methods and Results

Using United Network for Organ Sharing data (2004–2015), we analyzed 17,361 adult heart transplant patients whose class I and II panel reactive antibodies were reported. Patients were divided into 4 groups: class I and II ≤25% (group 1); class I ≤25% and class II ˃25% (group 2); class II ≤25% and class I >25% (group 3); and both class I and II >25% (group 4). Outcomes assessed were treated rejection at 1-year mortality, all-cause mortality, and rejection-related mortality. Compared with group 1, only group 4 was associated with a higher risk of treated rejection at 1 year (odds ratio 1.31, 95% confidence interval [CI] 1.05–1.64), all-cause mortality (hazard ratio 1.24, 95% CI 1.06–1.46), and mortality owing to rejection (subhazard ratio 1.84, 95% CI 1.18–2.85), whereas groups 2 and 3 were not (P > .05).

Conclusions

Combined elevation in class I and II panel reactive antibodies seem to increase the risk of treated rejection and all-cause mortality, whereas risk with isolated elevation is unclear.

Section snippets

Patient Population

We performed a retrospective analysis of UNOS Organ Procurement and Transplantation Network registry of all adult patients (age ≥18 years) who underwent orthotopic heart transplantation between 2004 and 2015. Class I and class II PRA levels were being systematically reported from 2004. Patients with prior heart transplantation were excluded from the study. Of this cohort, both class I and class II PRA levels were reported in 17,361 patients and these patients were included in the study.

Given

Patient Population and PRA

Baseline characteristics of the patients are shown in Table 1. The median age of the cohort was 56 years (interquartile range 46–62 years) with 25% of the cohort being female. The median time on the waitlist was 83 days (interquartile range 24–234 days), and a significant number (85.6%) had >4 HLA mismatches.

The frequency of patients in each of the PRA groups was 88% for group 1, 3% for group 2, 6% for group 3, and 3% for group 4. Thus, 12% of transplanted patients were sensitized against class

Discussion

Currently, the relationship between pretransplant elevation in class I and class II PRA and post-heart transplant outcomes is unclear. To our knowledge this is the first report evaluating the differential impact of elevated class I and class II PRA on outcomes in heart transplant recipients. We found that, although sensitized patients are at risk for waiting longer on the waitlist, their post-transplant risk for poor outcomes seems to increase mainly in those patients who have combined

Conclusions

Combined elevation of class I and class II PRA is associated with increased risk of adverse outcomes such as treated rejection at one-year and all-cause mortality. Among this, the increased risk of treated rejection was driven by class I PRA and increased mortality driven by class II PRA. Hence, an integrated analysis of both PRAs provides superior information regarding clinically relevant outcomes.

All the authors contributed to conception and interpretation of data. JBIM and LB drafted of the

Declaration of Competing Interest

None

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