Atopic dermatitis, also known as eczema, affects millions of people in the United States. While there is yet no cure for the condition and its causes are not fully understood, new research has uncovered some of its genetic underpinnings, bringing us closer to discovering novel therapies.
Atopic dermatitis is a chronic, non-contagious inflammatory skin disorder. People who have eczema may also be prone to other viral or bacterial skin conditions. This happens because people with eczema do not have the proteins that normally protect healthy skin against infections.
The National Institute of Allergy and Infectious Diseases (NIAID) estimate that as many as 30 percent of U.S. individuals are affected by eczema. The condition strikes children and teenagers in particular.
While it is not yet known what causes eczema, researchers believe that a combination of genes and environmental factors drive the disease.
A team of researchers from the NIAID, together with scientists from other institutions, set out to analyze genetic sequences in people with severe eczema.
The co-senior and corresponding author of the study is Dr. Joshua Milner, chief of the Genetics and Pathogenesis of Allergy Section in the NIAID's Laboratory of Allergic Diseases.
As the authors of the new study point out, until now, few studies have found a single-gene cause for common allergic diseases.
CARD11 gene mutation may drive eczema
Dr. Milner and colleagues singled out eight people from four families that had mutations in the CARD11 gene. This gene encodes the instructions for producing the CARD11 protein, which has a key role in lymphocyte receptor signaling.
Some of the people in the study who had these genetic mutations also had other health problems, such as other infections, while some did not.
This suggested to the researchers that CARD11 mutations can lead to eczema without simultaneously causing comorbidities, as is often the case with immune system conditions.
In an attempt to understand precisely the mechanism through which CARD11 mutations lead to atopic dermatitis, the researchers conducted a series of experiments and studied cell cultures to examine the effect of the mutations on the CARD11 protein.
In each of the four families, the researchers found a different mutation that affected a separate area of the CARD11 protein. However, all of the mutations affected T cell signaling in a similar way.
T cells are a white blood cell type, which are essential for the body's immune response to infections.
Specifically, the researchers were able to detect two cell-signaling pathways that were disrupted by the mutations. These signaling pathways were no longer activated properly as result of the mutations.
Normally, one of these pathways is partially activated by glutamine, which is an amino acid - that is, a "building block of protein" - with key roles in immunity, brain function, and digestion.
The researchers were able to boost glutamine levels and thus "partially rescue" the cell-signaling defects caused by the genetic mutations that underpin eczema.
The next step for Dr. Milner and his team is to analyze the effect of taking glutamine and leucine - a similar amino acid that activates the same cell-signaling pathways as glutamine - supplements in people who have atopic dermatitis, with and without the newly discovered genetic mutations.