Researchers Discover New Inflammatory Disease Affecting Young Children


The discovery of otulipenia suggests a strong link between ubiquitin and inflammation.

Although we usually associate inflammation with pain, discomfort, and many chronic diseases, it isn’t necessarily a bad thing.

When bacteria or viruses invade the body, a complex biological response involving a biochemical cascade begins. This entirely normal process, involving various types of immune cells, clotting proteins, and signaling molecules, is called acute inflammation. It’s the body’s protective response to injury or infection that directs the widening of blood vessels, resulting in an outflow of fluid and immune cells into surrounding tissues.

Unfortunately, chronic inflammation sometimes occurs and continues with no resolution. In this case, the body’s immune system mistakenly initiates an inflammatory response, even though there’s no apparent injury or invasion to fight off.

An international team of scientists has discovered a new inflammatory condition called otulipenia that primarily affects young children. This rare and often lethal disease results in the malfunction of OTULIN, a single gene on chromosome 5. When OTULIN’s functioning properly, the body can effectively develop blood vessels and fight infection with the mobilization of cells and proteins.

The team, which included researchers from the US National Institutes of Health, found that the OTULIN gene was abnormal in 4 sick children from Pakistani and Turkish families with unexplained skin rashes and inflamed joints. Upon further study, the team found a problem in the way ubiquitin—a small protein critical to the regulation of many other proteins in the body, including immune molecules—is removed from the body. This inability to remove the ubiquitin proteins from various molecules can cause an increased production of inflammatory cytokines, the chemical messengers that lead to inflammation.

The researchers soon discovered that children with this inflammatory disease who were treated with tumor necrosis factor (TNF) inhibitors responded favorably with diminishing inflammation, most likely because TNF is a chemical messenger involved in systemic inflammation.

TNF inhibitors are used to treat other chronic inflammatory diseases like rheumatoid arthritis, psoriatic arthritis, and juvenile arthritis. The drugs in this class include Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab), Cimzia (certolizumab pegol), and Simponi (golimumab).

In addition to discovering a new category of human inflammatory diseases caused by impaired ubiquitination, the researchers suggest their results could lead to the development of new therapies for patients with a wide range inflammatory diseases.


Zhou Q, et al. Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. Proc Natl Acad Sci U S A. 2016 Aug. pii: 201612594.

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