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September 9, 2016
Digest

Researchers Discover New Inflammatory Disease

NIH researchers have discovered a rare and sometimes lethal inflammatory disease—otulipenia—that primarily affects young children. Scientists have also identified anti-inflammatory treatments that ease some of the patients’ symptoms: fever, skin rashes, diarrhea, joint pain and overall failure to grow or thrive.

The just-discovered otulipenia is a rare and sometimes lethal inflammatory disease that causes fever, skin rashes, diarrhea and joint pain in young children.
The just-discovered otulipenia is a rare and sometimes lethal inflammatory disease that causes fever, skin rashes, diarrhea and joint pain in young children.

IMAGE: NHGRI

Otulipenia is caused by the malfunction of OTULIN, a single gene on chromosome 5. When functioning properly, OTULIN regulates the development of new blood vessels and mobilization of cells and proteins to fight infection. Researchers published their findings Aug. 22 in the early edition of the Proceedings of the National Academy of Sciences.

Contributing to the work were researchers from NHGRI, NIAID, NIAMS, NHLBI and the Clinical Center, along with colleagues in Turkey and the United Kingdom.

“The results have been amazing and life-changing for these children and their families,” said study co-author Dr. Daniel Kastner, NHGRI scientific director and head of NHGRI’s inflammatory disease section. “We have achieved the important goal of helping these young patients and made progress in understanding the biological pathways and proteins that are important for the regulation of the immune system’s responses.”

Cells use biological pathways to send and receive chemical cues in reaction to injury, infection or stress.

Otulipenia is one of several inflammatory diseases that occur when the immune system attacks the host’s own tissues. Inflammation is the body’s natural response to invading bacteria or viruses. The body releases chemicals that cause blood vessels to leak and tissues to swell in order to isolate a foreign substance from further contact with the body’s tissues. Inflammatory diseases affecting the whole body are caused by mutations in genes like OTULIN that are part of a person’s innate immunity (the cells and proteins present at birth that fight infections).

Stem Cell Therapy Heals Injured Mouse Brain

Scientists and clinicians have long dreamed of helping the injured brain repair itself by creating new neurons; an innovative NIH-funded study published Aug. 22 in Nature Medicine may bring this goal much closer to reality. A team of researchers has developed a therapeutic technique that dramatically increases the production of nerve cells in mice with stroke-induced brain damage.

The therapy relies on the combination of two methods that show promise as treatments for stroke-induced neurological injury. The first consists of surgically grafting human neural stem cells into the damaged area, where they mature into neurons and other brain cells. The second involves administering a compound called 3K3A-APC, which the scientists have shown helps neural stem cells grown in a Petri dish develop into neurons. However, it was unclear what effect the molecule, derived from a human protein called activated protein-C (APC), would have in live animals.

A month after their strokes, mice that had received both the stem cells and 3K3A-APC performed significantly better on tests of motor and sensory functions compared to mice that received neither or only one of the treatments. In addition, many more of the stem cells survived and matured into neurons in the mice given 3K3A-APC.

“This animal study could pave the way for a potential breakthrough in how we treat people who have experienced a stroke,” added Dr. Jim Koenig, a program director at NINDS, which funded the research. “If the therapy works in humans, it could markedly accelerate the recovery of these patients.”

Oxygen Can Impair Cancer Immunotherapy in Mice

Researchers have identified a mechanism in mice by which anti-cancer immune responses are inhibited within the lungs, a common site of metastasis for many cancers. This mechanism involves oxygen inhibition of the anti-cancer activity of T cells. Inhibiting the oxygen-sensing capability of immune cells, either genetically or pharmacologically, prevented lung metastasis. This research was conducted by Dr. Nicholas Restifo of NCI and colleagues at both NCI and NIAID. The findings appeared Aug. 25 in the journal Cell.

Metastasis is the cause of most cancer deaths. It has long been hypothesized that the process of cancer metastasis requires cooperation between spreading cancer cells and the cellular environment to which they spread. A key component of that environment is the local immune system, which can act to fight off invading cancer cells.

The researchers discovered that T cells, a type of immune cell, contain a group of oxygen-sensing proteins that act to limit inflammation within the lungs. This new research shows, however, that oxygen also suppresses the anti-cancer activity of T cells, thereby permitting cancer cells that have spread to the lungs to escape immune attack and establish metastatic colonies.

New Strategy Holds Promise for Detecting Bacterial Infections in Newborns

Researchers have shown it’s possible to diagnose a bacterial infection from a small sample of blood in infants 2 months of age or younger who have fevers.
Researchers have shown it’s possible to diagnose a bacterial infection from a small sample of blood in infants 2 months of age or younger who have fevers.

Researchers supported in part by NICHD have shown that it’s possible to diagnose a bacterial infection from a small sample of blood—based on the immune system’s response to the bacteria—in infants 2 months of age or younger who have fevers. With additional research, the new technique could be an improvement over the standard method, which requires isolating live bacteria from blood, urine or spinal fluid and growing them in a laboratory culture. The study appeared Aug. 23 in the Journal of the American Medical Association.

Health care providers who evaluate young infants with fevers have limited means to quickly and accurately diagnose whether or not an illness results from a bacterial infection. Determining if the illness is caused by bacteria may involve complicated medical procedures, such as a lumbar puncture (spinal tap). While they wait for the test results, physicians also may need to admit the infant for a lengthy hospital stay or prescribe antibiotics, which may later turn out to be unnecessary.

“The development of a fast and noninvasive diagnostic tool holds promise for better outcomes and lower treatment costs for young infants with fevers of unknown cause,” said Dr. Valerie Maholmes of NICHD.

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