Anti-ICAM3 monoclonal antibody, clone 3G9

DC-SIGN is a C- type lectin receptor of dendritic cells and is involved in the early stages of numerous infectious diseases. DC-SIGN is organized into a tetramer enabling multivalent interaction with pathogens. Once formed, the DC-SIGN-pathogen complex can be internalized into compartments of increasing acidity. We have studied the pH dependence of the oligomerization state and conformation of the entire extracellular domain and neck region. We present evidence for equilibrium between the monomeric and tetrameric states of the extracellular domain, which exhibits a marked dependence with respect to both pH and ionic strength. Using solution x-ray scattering we have obtained a molecular envelope of the extracellular domain in which a model has been built. Our results highlight the central role of the neck domain in the pH-sensitive control of the oligomerization state, in the extended conformation of the protein, and in carbohydrate recognition domain organization and presentation. This work opens new insight into the molecular mechanism of ligand release and points to new avenues to block the first step of this important infection pathway.

Background & AimsHepatopulmonary syndrome is a complication of chronic liver disease resulting in increased morbidity and mortality. It is caused by intrapulmonary vascular dilations and arteriovenous connections with devastating influence on gas exchange. The pathogenesis is not completely understood but evidence mounts for angiogenesis. Aims of this study were to identify angiogenic factors in serum of patients with hepatopulmonary syndrome and to study the possibility to predict its presence by these factors. MethodsMultiplex assays were used to measure the concentration of angiogenic factors in patients with (n=30) and without hepatopulmonary syndrome (n=30). Diagnosis was based on the presence of gas exchange abnormality and intrapulmonary vasodilations according to published guidelines. ResultsPatients with and without hepatopulmonary syndrome had similar MELD scores (median: 11.2 vs. 11.6; P=0.7), Child-Pugh score (P=0.7) and PaCO2 values (median: 35 vs. 37; P=0.06). PaO2 and P(A-a) O-2 gradient were significantly different (respectively median of 80 vs. 86, P=0.02; and 24 vs. 16, P=0.004). Based on area under the curve (AUC) data and P-values, the best predictors were vascular cell adhesion molecule 1 (VCAM1) (AUC=0.932; P<0.001) and intercellular adhesion molecule 3 (ICAM3) (AUC=0.741; P=0.003). Combining these factors results in an AUC of 0.99 (after cross-validation still 0.99). ConclusionsVCAM1 and ICAM3 might be promising biomarkers for predicting hepatopulmonary syndrome. Combining these factors results in an AUC of 0.99 and a negative predictive value of 100%. Determining the concentration of these biomarkers might be a screening method to detect hepatopulmonary syndrome. The use of these biomarkers should be validated in larger groups of patients.