Genetic Glitch may Cause Lupus

Lupus may be caused by a genetic fault present in a type of white blood cell, new research led by an Indian scientist has revealed.

According to the scientists, the findings may help in earlier diagnosis, finding a way to monitor patients' response to therapy and possibly a new way to treat the disease.

The results of the study, led by Dama Laxminarayana, Ph.D., assistant professor of internal medicine and senior author, involve an enzyme that "edits" and modifies the messages of genes before the protein-making process.

He said that in systemic lupus erythematosus, the normal editing process gets disturbed which leads to a shift in the balance of proteins, resulting in impaired functions in T cells, a type of white blood cell involved in the regulation of immune functions.

Lupus is a complex chronic autoimmune disorder that can range from a benign skin disorder to severe, life-threatening multisystem disease and is mainly characterised by impaired T cell function. It primarily affects women in the child-bearing years and is more common in blacks.

The current study focussed on 13 patients with lupus and eight healthy participants, and was based on Laxminarayana's earlier findings that 150-kDa ADAR1, one of the three enzymes involved in editing gene messages, is higher in the T cells of lupus patients compared to those without lupus. ADARs are ademosine deaminases that act on RNA.

In this study, it was found that the higher levels of 150-kDa ADAR1 alters the editing induced by two other ADAR enzymes and may cause an imbalance of proteins. While editing by the two other ADAR enzymes is a normal cellular process, it is 150-kDa ADAR1 that causes normal editing to go awry.

The findings indicated that essentially, too much 150-kDa ADAR1 results in an increase in the gene message of Phosphodiesterase 8A1 (PDE8A1), which is involved in the disruption of normal cell signaling and impairing cell function.

"150-kDa ADAR1 is the culprit. We are now working to find a safe way to block it," said Laxminarayana.

Not only would 150-kDa ADAR1 target the enzyme as a treatment strategy, it could also be used as a biomarker to detect the disease earlier, to monitor how patients respond to therapy, and to measure disease intensity.

The study is reported online in the journal Immunology.

Source-ANI
RAS/L