We have isolated three types of cDNAs encoding novel ␤1,3-N-acetylglucosaminyltransferases (designated ␤3Gn-T2, -T3, and -T4) from human gastric mucosa and the neuroblastoma cell line SK-N-MC. These enzymes are predicted to be type 2 transmembrane proteins of 397, 372, and 378 amino acids, respectively. They share motifs conserved among members of the ␤1,3-galactosyltransferase family and a ␤1,3-N-acetylglucosaminyltransferase (designated ␤3Gn-T1), but show no structural similarity to another type of ␤1,3-N-acetylglucosaminyltransferase (iGnT). Each of the enzymes expressed by insect cells as a secreted protein fused to the FLAG peptide showed ␤1,3-N-acetylglucosaminyltransferase activity for type 2 oligosaccharides but not ␤1,3-galactosyltransferase activity. These enzymes exhibited different substrate specificity. Transfection of Namalwa KJM-1 cells with ␤3Gn-T2, -T3, or -T4 cDNA led to an increase in poly-N-acetyllactosamines recognized by an anti-i-antigen antibody or specific lectins. The expression profiles of these ␤3Gn-Ts were different among 35 human tissues. ␤3Gn-T2 was ubiquitously expressed, whereas expression of ␤3Gn-T3 and -T4 was relatively restricted. ␤3Gn-T3 was expressed in colon, jejunum, stomach, esophagus, placenta, and trachea. ␤3Gn-T4 was mainly expressed in brain. These results have revealed that several ␤1,3-Nacetylglucosaminyltransferases form a family with structural similarity to the ␤1,3-galactosyltransferase family. Considering the differences in substrate specificity and distribution, each ␤1,3-N-acetylglucosaminyltransferase may play different roles.A family of human ␤1,3-galactosyltransferases (␤3Gal-Ts) 1 consisting of five members (␤3Gal-T1, -T2, -T3, -T4, and -T5) was recently identified (1-4). The first ␤1,3-galactosyltransferase (␤3Gal-T1), which catalyzes the formation of type 1 oligosaccharides, was isolated by us using an expression cloning approach (1). Expression patterns of ␤3Gal-T1 and type 1 oligosaccharides strongly suggested the existence of ␤3Gal-T1 homologs. For instance, type 1-derived oligosaccharides such as sialyl-Le a were known to be expressed in colon and pancreatic cancer cell lines, whereas expression of ␤3Gal-T1 was detected in brain, but not in cancer cells. Our early approach using Southern hybridization failed to detect the existence of ␤3Gal-T1 homologous genes. However, recent accumulation of nucleotide sequence information on human cDNAs and genes such as expressed sequence tags (ESTs) enabled us to search homologous genes that do not have high similarity as detected by hybridization, but show significant similarity. A homology search based on the nucleotide or amino acid sequence of ␤3Gal-T1 led to the isolation of ␤3Gal-T2, -T3, and -T4, indicating that ␤3Gal-Ts form a family (1-3).␤3Gal-T2 catalyzed a similar reaction, but showed different substrate specificity compared with ␤3Gal-T1. The activity of ␤3Gal-T3 has not been detected, whereas the corresponding mouse enzyme exhibits weak ␤3Gal-T activity for both GlcNAc and GalNAc (5). On the other...

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Background: Airway eosinophils are considered to play an important role in the pathogenesis of asthma. Interleukin-5 is believed to be a key cytokine for the development, proliferation and activation of eosinophils. Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody that depletes blood and airway eosinophils. We conducted a phase 2a study in South Korea and Japan to evaluate the effect of benralizumab in an East Asian population. The primary objective was to evaluate the effect of benralizumab in adults with uncontrolled eosinophilic asthma with 2-6 incidences of exacerbations in the past year using a medium/high dose of inhaled corticosteroids and long-acting β₂-agonists. Methods: This was a multicenter, randomized, double-blind, placebo-controlled study. The subjects (n = 106) were randomized into four groups: placebo (n = 27) or benralizumab 2 mg (n = 27), 20 mg (n = 26) and 100 mg (n = 26). Benralizumab or placebo were administered subcutaneously on weeks 0 (day 1), 4, 8, 16, 24, 32 and 40. The primary endpoint was the asthma exacerbation rate at week 52. Results: The asthma exacerbation rate was reduced by 33, 45 or 36% versus the placebo group when treated with 2, 20 or 100 mg of benralizumab, respectively. The percent mean change in forced expiratory volume at 1 s increased with each of the three doses in subjects treated with benralizumab. Conclusions: Benralizumab reduced asthma exacerbation and improved lung function and asthma control in adults with uncontrolled eosinophilic asthma.

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