Cystic fibrosis transmembrane conductance regulator functional evaluations in a G542X+/- IVS8Tn:T7/9 patient with acute recurrent pancreatitis

Figure 1 Results of standardized cystic fibrosis transmembrane conductance regulator functional test. Intestinal current measurement tracings from the controversial clinical case (presented herein), cystic fibrosis (CF) patients with pancreatic insufficiency-CF or pancreatic sufficiency-CF and control (non-CF donor). As shown in the top panel, there were positive tissue responses to forsk/IBMX: Forskolin/3-isobutyl-1-methylxanthine, Carbachol and Histamine clearly visible in acute recurrent pancreatitis and not consistent with CF diagnosis. ARP: Acute recurrent pancreatitis; CF: Cystic fibrosis; PI-CF: Pancreatic insufficiency-cystic fibrosis; PS-CF: Pancreatic sufficiency-cystic fibrosis.

Figure 2 Results of cystic fibrosis transmembrane conductance regulator functional assays. A: Membrane depolarization by single cell fluorescence analysis performed in monocytes with (black trace) and without (white trace) stimulus added at 5 min. The cystic fibrosis (CF) index was calculated as reported[10]; B: Normalized volume increase of individual organoids obtained during Forskolin-induced swelling assay. Organoids were obtained from the acute recurrent pancreatitis patient carrying the mutation G542+/-, a non-CF subject with or without pre-incubation with cystic fibrosis transmembrane conductance regulator-inh72 and with stimulation with the potentiator VX770, and a CF patient. Box and whisker plots (10^th-90^th percentiles) correspond to the normalized volume increase with respect to the baseline for each subject; the midline in boxes indicates median. Symbols indicate significant differences (one way-ANOVA; ^aP < 0.05; ^bP < 0.02) identified by Dunn’s method to compare all groups vs the non-CF control. CFTR: Cystic fibrosis transmembrane conductance regulator; CF: Cystic fibrosis; CFI: Cystic fibrosis index; FIS: Forskolin-induced swelling.