Fig. 3.
Sphingolipid-related SNPs associate with cellular islet autoimmunity in individuals with type 1 diabetes. Proliferation of T cells specific for GAD65, PPI, IA-2 and INS-DRiP in PBMCs freshly isolated from individuals with type 1 diabetes. Patients were divided into risk groups based on sphingolipid-related genetic risk: low (GRS=0.11–0.14, n=20); intermediate (GRS=0.14–0.16, n=37) and high (GRS >0.16, n=14). Data were normalised by natural log-transformation. SI ≥3 is considered positive. Tukey boxplots are shown. (a) Cumulative proliferation of islet-specific T cells (SISUM =SIGAD65+SIPPI+SIIA-2+SIINS-DRiP) in patient-risk groups. (b) Proliferation of T cells in patient-risk groups plotted per islet-autoantigen. Dashed line indicates SI=3. (c) Percentage of patients within each risk group with positive T cell proliferation responses (SI ≥3) plotted per islet-autoantigen. Light grey bars, low GRS; medium grey bars, intermediate GRS; dark grey bars, high GRS. (d, e) Proliferation of PPI-specific T cells in heterozygous and homozygous carriers of the (d) rs12150079 or (e) rs33988101 risk allele vs non-carriers of the respective risk allele. *p<0.05; **p<0.01. One-way ANOVA with Tukey’s multiple comparisons, χ2 two-proportions Z test and two-tailed unpaired Student’s t test