Current International Intestinal Transplant Registry Data Is Insufficient For Immunologic Risk Assessments

Background: The International Intestinal Transplant Registry (IITR) is an encounter-based database developed by an international consortium performing intestinal transplantation (IT). The goal of this study was to characterize available immunological data and evaluate factors associated with rejection. Methods: Demographic, outcomes, and serologic HLA data from donor/recipient pairs was obtained from the IITR. HaploStats was used to convert serological data to high-resolution, four-digit HLA sequences. Eplet mismatch analysis was performed using HLAMatchmaker. Highest and lowest deciles were compared for reported DSA correlations using a Mann-Whitney non-parametric t-test for all class I HLA, -DR1/3/4/5, and –DQB1. Results: Data from 228 ITs with a median follow-up time of 28 months (range 0–103 months) was evaluated. 31 (13.6%) individuals lacked any HLA typing, 17(7.4%) had molecular data, and 180 patients (79.0%) had recorded serological typing. Of 197 patients with HLA typing data, 62 (31.5%) were excluded for lack of DSA follow-up, 9 (4.6%) for preformed DSA, 13 (6.6%) for survival less than 24 hours, and 6 (5.3%) due to missing HLA-DQ typing that could not be imputed with confidence. Of the remaining 107, 35 (32.7%) had DSA reported post-transplant. Time to DSA detection was available for 28 of 35 (87.5%) individuals revealing a broad timeline with a median of 0.57 months (range 4–1097 days). With the available data, there was no difference in graft (p = 0.89) or patient survival (p = 0.54) between those who reported post-transplant DSA and those who did not. Comparing the highest and lowest 20th percentiles of HLA eplet mismatch scores, we found no difference in reported DSA development, rejection, graft survival, or patient survival for antibody-verified class I, class II (-DR1/3/4/5, -DQA1/DQB1), HLA-DR1/3/4/5, and HLA–DQA1/DQB1 (data summarized in Figure 1). Of note, the associations of the outcomes were strongest when investigating HLA class II, although they did not reach significance. Discussion: There is strong evidence that HLA eplet mismatch scores are correlated with post-transplant DSA development and rejection. Unfortunately, the study of this question in the IITR is limited by the quality and completeness of HLA and DSA data. Moreover, early DSA detection within the first post-transplant month may reflect limited pre-transplant screening and under appreciation of preformed HLA immune memory. To develop multicenter, data-based guidance for immunological risk assessment and immune monitoring, we must first improve the completeness of the registry immunological dataset.TABLE 1.: HLA eplet mismatch summary using Mann-Whitney non-parametric t-test to compare the 20th and 80th percentiles for HLA class I, class II (-DR1/3/4/5, -DQA1/DQB1), HLA-DR1/3/4/5, and HLA–DQA1/DQB1 for DSA development, rejection, graft survival, and patient survival.