It has been shown that afucosylated antibodies have 100-fold increased ADCC compared to the fucosylated ones 3. The fucosylation of N-glycans is known to negatively impact the antibody dependent cellular cytotoxicity (ADCC) of IgG 3, 4. N-glycosylation is a critical quality attribute for therapeutic monoclonal antibodies (mAbs), since it affects the drug efficacy, safety, and pharmacokinetic properties 1, 2. The core structure is further decorated with various sugar like fucose, bisecting GlcNAc, galactose and sialic acid to form a complex-type bi-antennary glycan. The Fc region of IgGs possesses two identical N-glycans which are composed of a core heptasaccharide with three mannoses and two N-acetylglucosamine (GlcNAc). The various N-glycan structures and the method for producing them in this work provide opportunities to study the glycan structure-and-function and develop novel recombinant antibodies for addressing different therapeutic applications. In addition, antibodies with various tri-antennary N-glycans were obtained for the first time by overexpressing MGAT5 alone or in combination with B4GalT1 and ST6Gal1. Combinatorial overexpression of B4GalT1 and ST6Gal1 produced antibodies containing more than 70% sialylated bi-antennary N-glycans. Overexpressing B4GalT1 gene alone in the CHO cells produced antibodies with more than 80% galactosylated bi-antennary N-glycans. The bottlenecks in the N-glycosylation pathway were identified and then released by overexpressing single or multiple critical genes. In order to minimize the clonal variations, we used recombinase-mediated-cassette-exchange (RMCE) technology to overexpress a panel of 42 human glycosyltransferase genes to screen their impact on antibody N-linked glycosylation. To improve N-glycan processing, glycosyltransferase genes have been traditionally overexpressed in CHO cells to engineer the cellular N-glycosylation pathway by using random integration, which is often associated with large clonal variations in gene expression levels. The N-glycan structures on antibodies are incompletely processed in wild-type CHO cells due to their limited glycosylation capacity. It usually occurs due to normal retrograde filling of renal veins and here the layering will be vertical as opposed to horizontal in IVC layering sign.Therapeutic antibodies are decorated with complex-type N-glycans that significantly affect their biodistribution and bioactivity. The managing physicians should be notified quickly to institute quick definitive therapy when these CT findings are present because they indicate cardiac failure. This condition has been described previously after cardiogenic shock, diastolic dysfunction, myocardial infarction and cardiac tamponade. It depends on density, specific gravity and injected volume of the contrast agent. Contrast agents are heavier than blood and hence accumulate in dependent parts of venous system leading to dependent venous pooling. However, in cases of cardiac failure there is decreased arterial and venous blood flow due to failure of forward flow of blood. In normal physiological state specific gravity has no effect on contrast agent dynamics. The physiological basis of IVC layering or pooling has been described previously. CT depicted the presence of blood contrast level in IVC in all cases with reflux of contrast into hepatic veins and liver parenchyma. We have demonstrated different cases with IVC contrast level sign in patients with circulatory shock, RV dysfunction and impending cardiogenic shock.
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