Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II

Figures

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  Figure 1. HLA-EMMA total amino acid mismatch (AAMM) (A-C) and solvent-accessible amino acid mismatch (SAAAMM) (D-F) for 274 pediatric heart transplant cases. Graphs show mismatches for all HLA loci tested: Class I + Class II (A, D) Class I (B, E), and Class II (C, F). The Pearson’s correlation coefficient rho (r) is stated on each plot.

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  Figure 2. Scatter plots showing PIRCHE-II score vs HLA-EMMA solvent-accessible amino acid mismatch (SAAAMM) score. Data from 100 transplant patients assessed for newly formed post-transplant DSA for each category (Class I, DR, DQ) (A-C) and ABMR (D-F) development. Datapoints for the patients that experienced the indicated post-transplant clinical event are colored red. Vertical lines represent the SAAAMM cut-off and horizontal lines represent the PIRCHE-II cut-off. Lines were drawn based on quantile analysis (see methods) using the red datapoints. Numbers on the graph indicate the numeric value of the cut-off for developing DSA (A-C) or ABMR (D-F).

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  Figure 3. Kaplan Meier survival curves showing risk stratification using cut-offs determined for solvent—accessible amino acid mismatch (SAAAMM) load generated via HLA-EMMA. Survival curves for Freedom from donor-specific antibody in Class I (A), DRB1/3/4/5 (B), and DQA1/DQB1 (C), and Freedom from antibody-mediated rejection in Class I (D), DRB1/3/4/5 (E), and DQA1/DQB1 (F) were plotted for 100 patients. The blue lines/labels represent low-risk groups, and the red lines/labels represent high-risk groups. Numbers in the table below represent the number of patients in each category at the indicated timepoint.

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  Figure 4. Box and whisker plots of PIRCHE-II score values grouped by HLA-EMMA solvent-accessible amino acid mismatch (SAAAMM) score bins for Class I (A), DRB1/3/4/5 (B), and DQA1/DQB1 (C). Pearson’s correlation coefficient is reported based on correlation of the individual values for PIRCHE-II and SAAAMM.

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  Figure 5. Kaplan Meier survival curves showing patients’ risk stratified using cut-offs determined for HLA-EMMA solvent-accessible amino acid mismatch (SAAAMM) and PIRCHE-II score. Survival curves for Freedom from donor-specific antibody in Class I (A), DRB1/3/4/5 (B), and DQA1/DQB1 (C), and Freedom from antibody-mediated rejection in Class I (D), DRB1/3/4/5 (E), and DQA1/DQB1 (F) were plotted for 100 patients. Stratification was performed by placing patients into three risk categories: High) patients with an above cut-off score for both algorithms (red line), Intermediate) patients with an above cut-off score by one of the two algorithms and a below cut-off score for the other (green line), Low) patients with below cut-off scores from both algorithms (blue line). Numbers in the table below each graph represent the number of patients in each category at the indicated timepoint. Log rank p-values are reported for all three risk categories (high, intermediate, and low; bottom left of graphs) or high versus low + intermediate (top right of graph).