Clinical trial assesses anti-FGF23 for treating X-linked hypophosphatemia
X-linked hypophosphatemia (XLH) is a heritable form of rickets that results from mutations in the gene encoding the phosphate regulating endopeptidase (PHEX). Unlike diet-associated forms of rickets, XLH cannot be ameliorated by vitamin D ingestion. XLH patients have increased serum levels of FGF23, which decreases both inorganic phosphate (Pi) and the activated form of vitamin D. In this issue of the Journal of Clinical Investigation, Thomas Carpenter and colleagues at Yale University evaluated the effectiveness and safety of an anti-FGF23 antibody (KRN23) in a small cohort of XLH patients. A single dose of KRN23 administered intravenously (i.v.) or subcutaneously (s.c.) improved renal phosphate reabsorption, and increased serum Pi and activated vitamin D concentrations, and s.c. administration provided benefit for a longer duration than i.v. dosing. These findings, along with a favorable safety profile, indicate that KRN23 should be further evaluated for use in XLH patients.
TITLE: Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia
AUTHOR CONTACT: Thomas CarpenterDept. Of Pediatrics (Endocrinology), New Haven, CT, USAPhone: 203-785-6526; Fax: 203-737-4290; E-mail: thomas.carpenter@yale.edu
View this article at: http://www.jci.org/articles/view/72829
Altered glycosylation patterns protect tumors from NK cells
Compared to other diseased cells, malignant tumor cells often exhibit modified surface glycosylation patterns, potentially altering recognition by host immune cells. Natural killer (NK) cells are sentinels of cancer immunosurveillanc system and express multiple receptors that allow for discrimination between healthy and malignant cells. In this issue of the , Stephan von Gunten and colleagues at the University of Bern determined that ligands of the inhibitory sialic acid-binding lectins Siglec-7 and Siglec-9 are expressed on the surface of multiple tumor cell types, and that expression of these ligands protects tumor cells from NK cell responses. Evaluation of NK cells in healthy donors revealed the presence of a Siglec-9-expressing cytotoxic NK cell population with enhanced chemotactic potential. Interestingly, the Siglec-9-expressing NK cell population was reduced in peripheral blood from patients with colon adenocarcinoma and malignant melanoma. These data suggest that targeting Siglec-7 and Siglec-9 ligands may enhance NK cell-based cancer therapies.
TITLE: Interactions between Siglec-7/9 receptors and ligands influence NK cell–dependent tumor immunosurveillance
AUTHOR CONTACT: Stephan von GuntenUniversity of Bern, Bern, CHEPhone: +41 31 632 32 98; Fax: +41 31 632 49 92; E-mail: stephan.vongunten@pki.unibe.ch
View this article at: http://www.jci.org/articles/view/65899
ALSO IN THIS ISSUE:
IMMUNOLOGY
TITLE: IL-7 receptor blockade following T cell depletion promotes long-term allograft survival
AUTHOR CONTACT: Hoa-Le MaiINSERM, Nantes, FRAPhone: 33240087410; Fax: 33240087411; E-mail: Le.Hoa-Mai@univ-nantes.fr
View this article at: http://www.jci.org/articles/view/66287
TITLE: Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation
AUTHOR CONTACT: Markus HeimUniversity Hospital Basel, Basel, , CHEPhone: 011 41 61 265 33 62; E-mail: markus.heim@unibas.ch
View this article at: http://www.jci.org/articles/view/70408
MICROBIOLOGY
TITLESoluble TNFRp75 regulates host protective immunity against Mycobacterium tuberculosis
AUTHOR CONTACT: Muazzam JacobsUniversity of Cape Town, Cape Town, , ZAFPhone: +27214066078; E-mail: muazzam.jacobs@uct.ac.za
View this article at: http://www.jci.org/articles/view/45005
NEUROSCIENCE
TITLE: Familial Alzheimer's disease–associated presenilin-1 alters cerebellar activity and calcium homeostasis
AUTHOR CONTACT: Markus GlatzelCenter for Diagnostic, University Medical Center Hamburg-Eppendorf, Hamburg, DEUPhone: ++49-40-7410-57583; E-mail: m.glatzel@uke.de
View this article at: http://www.jci.org/articles/view/66407
ONCOLOGY
TITLE: Hematopoiesis and RAS-driven myeloid leukemia differentially require PI3K isoform p110α
AUTHOR CONTACT: Kira GritsmanDana Farber Cancer Institute, Boston, MA, USAPhone: 617-459-7585; Fax: 617-632-4770; E-mail: kgritsman@partners.org
View this article at: http://www.jci.org/articles/view/69927
TITLE: Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma
AUTHOR CONTACT: David CarboneThe Ohio State University Medical Center, Columbus, OHPhone: 617-632-4786; E-mail: david.carbone@osumc.edu
View this article at: http://www.jci.org/articles/view/72763