The cutting edge genome technology led to clinical improvements through a customized treatment to a child with a rare incurable autoimmune disorder
The cutting edge genome technology led to clinical improvements through a customized treatment to a child with a rare incurable autoimmune disorder
- A glimpse of future medicine that cures a rare diseases through genomics
- Identifying the cause with whole exome sequencing and succeeded in the customized treatment of a 14-year old girl with a systematic autoimmune features
The latest genome test identified the cause and led to a successful customized treatment to a patient with a rare incurable autoimmune bowel disease.
A research team led by Professors Jae Sung Ko and Jin Soo Moon of the Department of Pediatrics & Adolescent Medicine at the Seoul National University Child's Hospital, Professor Murim Choi of the Department of Biomedical Sciences at the Seoul National University College of Medicine, and Dr. Park Sung-gyu at the Gwangju Institute of Science and Technology (GIST) has recently published the study results in the latest issue of the Journal of Allege and Clinical Immunology (IF=11.5), a prestigious international journal in immunology.
Kim 00 (14) had autoimmune enteropathy in which her own immune cells attacked enterocytes. As this disease occurs in less than one in 100,000 people, it is a rare disease without a cure.
She has suffered from chronic diarrhea since she was a three-month old baby and was diagnosed with autoimmune bowel disorder at age four. Since then, she has also suffered from pernicious anemia and autoimmune hepatitis and was treated for frequent infection accompanied by pancytopenia. Due to the chronic immune bowel disorder, she was diagnosed with gastric cancer through endoscopy at age twelve and underwent gastrostomy.
These symptoms are complications caused by a dysfunction of the immune system in which her immune system mistakenly recognizes enterocytes as foreign and attacks them. The medical team administered diverse kinds of immunosuppressive agents, but gained no positive outcomes.
The research team did a search of well-known causative genes, but could not pinpoint an exact cause. That's why whole-exome sequencing (WES) was conducted to analyze unknown genomic mutations from entire human gene set.
WES is a next-generation genomic analysis technique, in which the whole sequence of a gene can be analyzed at once to diagnose around ~20,000 genetic factors.
As a result, a mutation was found in CTLA4 (Cytotoxic T-lymphocyte antigen 4), a gene that controls the autoimmune reaction. The mutation disables the CTLA4's function to cause an autoimmune reaction.
The research team administered her with Abatacept which is an agent used to reinforce the CTLA4 function, based on the results of her WES test. This is originally used as a medicine to alleviate severe rheumarthritis symptoms.
Consequently, the researchers observed a significant improvement in her anemia and bowel symptoms. Diarrhea decreased by 67% and anemia improved to a point where transfusion was not required, so that she could end the three years hospitalization. Now she receives treatment as an outpatient. An additional reaction test also showed that the immune cells' function in her blood vessels was substantially improved by the drug treatment.
Professor Jin Soo Moon said, "This study is significant in that it discovered the causative gene of a specific disease using WES which is the latest genomic analysis technique to successfully allow a customized treatment.
The research team plans to evolve the customized treatment based on the outcomes of this study for pediatric patients with incurable gastrointestinal and liver disorders. The team especially focused on inflammatory bowel disease such as Crohn's disease and the genetic liver disease