Heterozygous SDHB neutrophils display a specific metabolic signature and enhanced survival. (A) Plasma succinate concentrations were determined for 97 healthy controls (HC) and 19 patients with germ line mutations in SDHB. Filled, half-filled, and open circles represent patients without, with previous, and with current tumors, respectively. Solid lines represent median values, and dashed lines represent upper and lower limits of reference. (B-E) Human peripheral blood neutrophils from healthy controls (HC) and SDHBx patients were studied in parallel. (B) Relative metabolite abundance. Freshly isolated neutrophils were lysed in methanol, the liquid phase was subjected to gas chromatography–mass spectrometry, and relative quantification of 20 key metabolic intermediaries was performed. Data represent mean ± SEM, n = 3. (C) Succinylation. Freshly isolated neutrophil lysates were separated by SDS-PAGE, and membranes were probed for succinylated protein expression relative to β-actin control; blot is representative of n = 3. (D-E) Apoptosis. Neutrophils were cultured for 20 hours in normoxia or hypoxia, and apoptosis was determined by morphology (D) and flow cytometry (Annexin V) (E). Solid bars represent mean; P values were determined by Mann-Whitney U test (A), unpaired Student t test (B), or 2-way ANOVA (D-E). ANOVA, analysis of variance; PAGE, polyacrylamide gel electrophoresis; SDS, sodium dodecyl sulfate; SEM, standard error of the mean.