Understanding Roots of Inflammatory And Auto-immune Disorders

Investigating a new rare childhood disorder similar to other inflammatory bowel diseases help us to create a new molecular roadmap relevant to understanding and treating inflammatory disorders.

The genetic cause of a rare childhood disorder that mimics inflammatory bowel disease is discovered. This finding may help to uncover the roots of other inflammatory and autoimmune disorders.

A team of researchers from Yale University investigated a mysterious case of a young boy with abdominal pain, intermittent bouts of fever, diarrhea over multiple days and canker sores in his mouth. The study is published in the journal Nature Immunology.

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‘A rare childhood disorder, X-linked deficiency in ELF4d helps in knowing the origin of inflammatory disease.’

Using genome sequencing of the child and his healthy parents, they revealed that the boy had a genetic defect that blocked ELF4, a transcription factor on the X chromosome that regulates expression of a large number of other genes.

Then, the research team identified two other male children with similar symptoms who also had ELF4 gene variants. This disorder is now termed “Deficiency in ELF4, X-linked,” or DEX for short. Now, an increasing number of cases are being identified.

Inflammatory diseases caused by a single gene mutation affect about 1 out of every 5,000 children.

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“It is very exciting to start with patients who are sick and discover an unexpected new gene with a fundamental role in regulating inflammation.” said Carrie Lucas, an assistant professor of immunobiology at Yale School of Medicine.

According to the researchers, the symptoms experienced by the children in the study were similar to those associated with other inflammatory bowel diseases is thought to be caused by an overactive immune system response that damages tissues of the host

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After identifying the ELF4 variant, they studied its effects in cultured cells from patients, as well as in mice using CRISPR gene-editing to introduce patient-derived ELF4 mutations.

They confirmed that the variant disrupted ELF4 function, and resulted in elevated inflammatory responses of a variety of immune cell types. The widespread effects of the variant suggest ELF4 and its target genes likely play a role in regulating inflammation in multiple diseases.

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This gives us the opportunity to identify and study the effects not only of ELF4 but also the genes it regulates across immune cell types and inflammatory disease phenotypes. This will help us to create a new molecular roadmap relevant to understanding and treating human diseases.

Source-Medindia