The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Friday Science Review: January 20, 2012

Genetic Basis of Jr(a)- Phenotype Discovered

University of Manitoba ♦ Published in Nature Genetics, January 15, 2012

The medical community has been aware of the Jr(a) antigen on red blood cells for quite some time. Roughly 40 years ago it was shown that a small group of individuals created antibodies against this protein motif. In the presence of normal red blood cells the antibodies produced by Jr(a)- individuals react quite vigorously. During transfusion it is important that donor blood does not contain Jr(a) antibodies because they can lead to negative transfusion reactions that are harmful to the recipient. In this recent study, investigators isolated the genetic component responsible for the Jr(a)- phenotype. Carrying out single nucleotide polymorphism analysis, researchers discovered a nearly 400 thousand base pair null region in Jr(a)- individuals that contained the gene ABCG2.

Cutting to the Core of Systemic Immune Response

Ontario Cancer Institute ♦ Published in Science, January 13, 2012

The human body has become adept at regulating pathogens. However, this evolutionary trait also has its down sides. Extreme innate immune response can cause systemic inflammatory reactions that can prove fatal. This recent study out of Tak Mak’s lab identifies a mechanism by which animals induce innate immune response following exposure to foreign pathogens. Tumour necrosis factor alpha (TNF-α) mediates septic shock through its release from cell membranes. This release process is regulated by an enzyme known as TNF-α convertase. Researchers discovered that this enzyme’s maturation and trafficking is controlled by iRhom2. Sure enough, mice deficient in iRhom2 displayed an ability to circumvent lethal doses of bacterial lipopolysaccharide.

Conditions characterized by systemic immune response are some of the hardest to go after in the clinic. As an indication, sepsis has been a graveyard, with only a few of some 40 clinical studies showing any efficacy in the last two decades. Identifying general systemic pathways, like that involving iRhom2, will be critical in creating therapeutics for these complex conditions in the future.

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