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. Author manuscript; available in PMC: 2020 Jul 1.
Published in final edited form as: J Allergy Clin Immunol. 2019 Feb 16;144(1):183–192. doi: 10.1016/j.jaci.2019.01.045

Figure 1. HLA-A*32:01 is strongly associated with vancomycin DRESS.

Figure 1.

A. 19/23 (83%) DRESS cases carried HLA-A*32:01 compared with 0/46 (0%) of the matched vancomycin tolerant controls (p=1×10–8, conditional logistic). If analyses are restricted to immunologically confirmed cases, then 11/12 (92%) vancomycin ELISpot positive patients carried HLA-A*32:01 compared with 0/24 (0%) of the BioVU matched controls (p=9×10–7, conditional logistic). HLA-A*32:01 carriage in all identified vancomycin DRESS cases and immunologically confirmed cases was also very significantly overrepresented compared to HLA-A*32:01 carriage in the entire BioVU cohort (6.3%) (p=2×10–16 and p=2=7×10–13 respectively, exact binomial tests). There was no significant difference in HLA-A*32:01 carriage between the vancomycin tolerant populations and the BioVU cohort (p=0.12 for all controls, p=0.40 for controls matched to immunologically confirmed cases, exact binomial tests). Additionally, there was no significant difference in HLA-A*32:01 carriage between the immunologically confirmed vancomycin DRESS cases and those that were not immunologically confirmed (p=0.32, Fisher’s exact test). All analyses shown included Bonferroni correction for multiple comparisons. B. IFN-γ release ELISpot results after 18-hour incubation with vancomycin at concentrations of 250 µg/mL (grey) or 500 µg/mL (black) using peripheral blood mononuclear cells from vancomycin DRESS patients. Controls included cells from vancomycin-naïve, HLA-A*32:01 positive healthy donors (n = 3) including the son of case patient 18 and the vancomycin skin test negative control C50, an HLA-A*32:01 positive individual tolerant of 4 weeks of vancomycin (n = 1), patients who had developed a non-DRESS immune-mediated adverse reaction to vancomycin (n = 5) and non-HLA matched healthy donors (n = 4). Means of the replicates are plotted. In patients with multiple blood draws at time points distant from the reaction, ELISpot results from the first blood draw are plotted. 12/14 (85.7%) DRESS cases had a positive vancomycin ELISpot compared to none of the controls (p=0.005 (DRESS vs. HLA-A-32:01 positive controls), p=0.002 (DRESS vs. non-DRESS ADRs), p=0.005 (DRESS vs. non-HLA matched healthy donors)). Positive results are those above the dotted line intersecting the y-axis at 50 SFU/million cells. Differences in proportion of positive responses between groups were assessed using Fisher’s exact tests. Patient and control PBMCs were also stimulated with vancomycin at concentrations of 5 µg/mL and 50 µg/mL and exhibited a dose-dependent response (data not shown). Legend: HLA, human leukocyte antigen; Vanc, vancomycin; DRESS, drug reaction with eosinophilia and systemic symptoms; SFU, spot-forming units; IM-ADR, immune-mediated adverse drug reaction.