Genetic Key to Lupus Shows Potential of Personalized Medicine

DNA sequencing of a systemic lupus erythematosus (SLE) patient has identified a specific genetic mutation that is causing the disease, opening the way for personalized treatments.

The development shows that for the first time, it is feasible for scientists to identify the individual causes of SLE in patients by using DNA sequencing, allowing doctors to target specific treatments to individual patients.


A multidisciplinary team of scientists at the Australian National University (Canberra, Australia) performed whole exome sequencing in a four year old female with early-onset SLE and conducted biochemical analysis of the putative defect. Whole exome sequencing offers the possibility of identifying rare alleles responsible for disease in such cases as the genetic contribution to disease is most likely to be greatest in cases with early onset and severe phenotypes.

Whole exome sequencing of the female patient with cerebral lupus, who had suffered a stroke at the age of four, identified a rare, homozygous mutation in the Three Prime Repair Exonuclease 1 (TREX1) enzyme that was predicted to be highly deleterious. The TREX1 R97H mutant protein had a 20-fold reduction in exonuclease activity and was associated with an elevated Interferon alpha (IFN-α) signature in the patient. The discovery and characterization of a pathogenic TREX1 in the proband has therapeutic implications in that the patient is now a candidate for neutralizing anti-IFN-α therapy.

Carola G Vinues, LMS, PhD, a professor of in the department of Pathogens and Immunity and senior author of the study, said, “This is the new age of personalized medicine. This study shows that it is possible to unravel the detailed and individual genetic causes of lupus in individuals. Lupus is a heterogeneous disease and patients can experience a number of different symptoms. We believe that there are different genetic causes of lupus. Understanding these defective genes and pathways in each individual will help tailor treatments.” The patient's treating clinician, Jeffrey Chaitow, MBBCh, FRACP, said his young patient, now 10 years old, still needs regular steroids and immune suppressive drugs each day. The study was published online in August 2014 in the journal Arthritis & Rheumatology.

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