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Doctors first saved the life of a boy with a genetic auto-inflammatory disease. To do this, they used a cure for rare blood cancer, which suppresses the activity of immune cells. Now the boy is already more than three years old, while all his predecessors with the same mutation did not live up to seven months. Report published In the magazine The New England Journal of Medicine.
Interferons are a group of proteins that cells produce in response to a viral infection. By themselves, interferons for viruses are harmless, but trigger an immune response and inflammation, as a result of which the viruses die. At the same time, interferons can also inhibit the inflammatory process so that it does not last too long and does not lead to damage to healthy tissues.
The JAK enzyme is responsible for the transmission of the “activating” signal from interferons (this name was originally decoded as just another kinase, “another kinase”, but then the enzyme was renamed to Janus kinase, Janus kinase). And the USP18 protein helps to inhibit inflammation, which itself binds to the cellular receptor for interferon and prevents JAK from receiving a signal.
Mutations in the gene USP18 lead to the development of interferonopathy – a disease in which excessive interferon signaling causes endless inflammation. It can not be considered an autoimmune disease, since immune cells are not sharpened to fight with the body’s own cells. Therefore, this condition is called autoinflammation. It can develop even before the baby is born and usually leads to his death in the late stages of pregnancy or in the first months of life.
An international team of doctors led by Abdullah Alangari from King Saud University described the case of a boy with a mutation in USP18whom they managed to keep alive. The child was born in Saudi Arabia, his parents were cousins, and he inherited a mutation in both copies of the gene. At the 38th week of pregnancy, during the ultrasound, the doctors noticed signs of pathology and prescribed an emergency cesarean section.
Already on the 13th day of life, the boy developed septic shock and multiple organ failure. The reason was a bacterium Bordetella pertussis in the airways and inflammation caused by it. Doctors quickly dealt with the infection with an antibiotic and discharged the patient home. But already on the 45th day he was again in the clinic – this time with skin necrosis in the place where the venous catheter used to be, it settled there Enterobacter cloacae. By this time, the boy had developed hydrocephalus, calcifications appeared in the brain, and a state of shock appeared again.
Then the doctors suggested that the boy could be saved with the help of the already known medicine. This is ruxolitinib – a drug that was developed to combat rare blood cancers. Its active substance blocks JAK, that is, it does what the mutant USP18 protein does not cope with. Two weeks after the boy started giving ruxolitinib, his condition improved greatly: hydrocephalus disappeared and the wound on his arm healed. After a month, the dosage was reduced, counting on remission, but the patient became worse again – breathing problems began. Therefore, he was prescribed a constant increased dose of the drug and was discharged home.
This case can serve as an example of how rarely used medicine can be useful in various diseases, including genetic ones. At the time of writing, the doctors had been monitoring the boy for three years, and he continued to take ruxolitinib. The authors of the work note that, despite small delays in development, their patient continues to grow normally.
We previously told a story girls named Milawho was less fortunate: for her rare genetic disease, there is no cure, and doctors had to create it from scratch.
Polina Loseva
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