Author Interviews, Neurological Disorders, Personalized Medicine / 19.06.2020 Interview with: Hänggi, PhD Chief Scientific Officer Polyneuron Pharmaceuticals What is the background for this study? Response: Anti-MAG neuropathy is a rare form of acquired demyelinating neuropathy. The disease onset normally presents after the age of 50 years and is 2.7 times more frequent in men than in women, with a prevalence of about 1 in 100,000. It is caused by the production of monoclonal anti-MAG IgM antibodies that recognize the HNK-1 epitope. The myelin-associated glycoprotein MAG is a mediator for the formation and maintenance of the myelin sheaths. There is strong evidence that the binding and deposition of anti-MAG IgM autoantibodies on myelin sheath is responsible for the demyelination, which clinically manifests itself as a peripheral neuropathy affecting primarily sensory nerves. However, the causes and the exact mechanisms behind the expansion of anti-MAG IgM producing B-cell and plasma cell clones are not fully understood. Most off-label treatments aim to reduce pathogenic autoantibody titers by depleting  autoantibody-producing B cell clones which interfere with antibody-effector mechanisms, or physically remove autoantibodies from the circulation. Most frequently, the anti-CD20 monoclonal antibody rituximab is used to treat anti-MAG neuropathy patients. However, all of these treatment options often lack of selectivity, efficiency, or can induce severe adverse effects in some patients. Polyneuron has designed PN-1007 to highly selectively target the IgM autoantibodies that cause anti-MAG neuropathy. PN-1007 is a glycopolymer that mimics the natural HNK-1 carbohydrate epitope found on myelin of peripheral nerves and binds to the circulating disease-causing antibodies. By eliminating these pathogenic antibodies, PN-1007 may protect the integrity of the neuronal myelin sheaths of anti-MAG neuropathy patients. (more…)
Allergies, Author Interviews, Pediatrics / 16.11.2018 Interview with: Eliane Abou-Jaoude, MD  Allergy and Immunology Fellow Henry Ford Health System Detroit, MichiganEliane Abou-Jaoude, MD  Allergy and Immunology Fellow Henry Ford Health System Detroit, Michigan What is the background for this study? Response: Early life exposure to diverse types of microbes is necessary for healthy immune development and may impact the risk for developing allergic disorders. Theoretically the transfer of parental microbes to their offspring during infancy can influence a child’s developing gut microbiome and subsequent immune response patterns. We wished to investigate whether parental pacifier cleaning methods, reported at 6-months of age, were associated with altered serum IgE trajectory over the first 18 months of life.  (more…)
Author Interviews, Infections / 09.03.2018 Interview with: Chih-Chi Andrew Hu, Ph.D. Associate professor in Microenvironment & Metastasis Program Wistar Institute What is the background for this study? What are the main findings?  Response: To help our body fight infections, B cells need to differentiate into plasma cells so that they can produce abundant antibodies against pathogens. Antibodies are folded and assembled in the endoplasmic reticulum (ER). Only those perfectly manufactured antibodies are allowed to be released from the ER and delivered to the outside of B cells to fight against the pathogens. IRE1 is a sensor protein that sits on the membrane of the ER, and can respond to B cell differentiation by activating the transcription factor called XBP1s. Activation of XBP1s allows B cells to expand the size of the ER and produce necessary chaperone proteins to help B cells manufacture perfect antibodies. By studying B cells that lack XBP1s, we discovered that these B cells produced dramatically increased levels of IRE1, and such IRE1 acquired phosphorylation at its serine 729 (S729).  (more…)
Author Interviews, Nature, Technology / 02.02.2018 Interview with: Dr. Sarav Rajan, PhD Scientist Antibody Discovery and Protein Engineering MedImmune What is the background for this study? What are the main findings? Response: During an infection, B cells (a type of white blood cell) create antibodies against antigens present on a pathogen. These cells can be extremely rare, and finding them among the millions of other cells is extremely challenging. Existing methods to examine B cells require a trade-off: either capture the full sequence repertoire by next-generation sequencing but functionally screen just a subset, or culture a subset of B cells and fully screen them. Instead, our method captures the complete repertoire within a typical blood draw and screens all its members to identify the rare antigen-positive antibodies. Using a new microfluidic approach, we recovered the antibody genes from one million B cells encapsulated in picoliter-scale droplets, breaking through a widely-published view that amplifying from single cells in such small volumes is inefficient. The resulting library seamlessly integrates into our high-throughput screening infrastructure to enable rapid isolation of desired antibodies. Using this method, we were able to isolate a panel of rare cross-reactive antibodies targeting influenza. (more…)