Assessing Pulmonary Perfusion in Emphysema Automated Quantification of Perfused Blood Volume in Dual-Energy CTPA

Objectives: The objective of this study was to determine whether automated quantification of lung perfused blood volume (PBV) in dual-energy computed tomographic pulmonary angiography (DE-CTPA) can be used to assess the severity and regional distribution of pulmonary hypoperfusion in emphysema. Materials and Methods: We retrospectively analyzed 40 consecutive patients (mean age, 67 13] years) with pulmonary emphysema, who have no cardiopulmonary comorbidities, and a DE-CTPA negative for pulmonary embolism. Automated quantification of global and regional pulmonary PBV was performed using the syngo Dual Energy application (Siemens Healthcare). Similarly, the global and regional degrees of parenchymal hypodensity were assessed automatically as the percentage of voxels with a computed tomographic density less than -900 Hounsfield unit. Emphysema severity was rated visually, and pulmonary function tests were obtained by chart review, if available. Results: Global PBV generated by automated quantification of pulmonary PBV in the DE-CTPA data sets showed a moderately strong but highly significant negative correlation with residual volume in percentage of the predicted residual volume (r = -0.62; P = 0.002; n = 23) and a positive correlation with forced expiratory volume in 1 second in percentage of the predicted forced expiratory volume in 1 second (r = 0.67; P < 0.001; n = 23). Global PBV values strongly correlated with diffusing lung capacity for carbon monoxide (r = 0.80; P < 0.001; n = 15). Pulmonary PBV values decreased with visual emphysema severity (r = -0.46, P = 0.003, n = 40). Moderate negative correlations were found between global PBV values and parenchymal hypodensity both in a per-patient (r = -0.63; P G 0.001; n = 40) and per-region analyses (r = -0.62; P < 0.001; n = 40). Conclusions: Dual-energy computed tomographic pulmonary angiography allows simultaneous assessment of lung morphology, parenchymal density, and pulmonary PBV. In patients with pulmonary emphysema, automated quantification of pulmonary PBV in DE-CTPA can be used for a quick, reader-independent estimation of global and regional pulmonary perfusion, which correlates with several lung function parameters

KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-C

Human killer cell immunoglobulin-like receptors (KIRs) are distinguished by expansion of activating KIR2DS, whose ligands and functions remain poorly understood. The oldest, most prevalent KIR2DS is KIR2DS4, which is represented by a variable balance between “full-length” and “deleted” forms. We find that full-length 2DS4 is a human histocompatibility leukocyte antigen (HLA) class I receptor that binds specifically to subsets of C1+ and C2+ HLA-C and to HLA-A*11, whereas deleted 2DS4 is nonfunctional. Activation of 2DS4+ NKL cells was achieved with A*1102 as ligand, which differs from A*1101 by unique substitution of lysine 19 for glutamate, but not with A*1101 or HLA-C. Distinguishing KIR2DS4 from other KIR2DS is the proline–valine motif at positions 71–72, which is shared with KIR3DL2 and was introduced by gene conversion before separation of the human and chimpanzee lineages. Site-directed swap mutagenesis shows that these two residues are largely responsible for the unique HLA class I specificity of KIR2DS4. Determination of the crystallographic structure of KIR2DS4 shows two major differences from KIR2DL: displacement of contact loop L2 and altered bonding potential because of the substitutions at positions 71 and 72. Correlation between the worldwide distributions of functional KIR2DS4 and HLA-A*11 points to the physiological importance of their mutual interaction