In an international genetic study of more than 3,000 women, researchers found evidence of an association between Lupus (systemic lupus erythematosus or SLE) and mutations in several different genes.
The findings, by scientists from Imperial College London and institutions in the USA and Sweden, will enable researchers to investigate the specific pathways and precise molecular mechanisms involved in developing Lupus, potentially opening up options for new therapies. Lupus is a complex condition, mostly affecting women, which frequently causes skin rash, joint pains and malaise, and which can also lead to inflammation of the kidneys and other internal organs.
The scientists discovered the strongest associations with Lupus in three genes: ITGAM, PXK, and one mutation within a gene KIAA1542, a gene whose function is not definitely known.
The ITGAM gene provides code for a molecule involved in a system, known as the complement system, which forms part of the body's immune response. Complement is a series of proteins in the blood which is designed to stick to the surface of bacteria and bugs in order to enable them to be attacked by the immune system.
The discovery of variations in the ITGAM gene in people with Lupus supports the idea that abnormalities in the way complement and antibodies bind to immune cells play a key part in the disease. It is already known that people with Lupus often have low levels of complement in their blood.
The role of the molecules encoded by the PXK gene and KIAA1542 genes in Lupus is less easy to predict, and the discovery of their association is more surprising to the researchers, opening up new avenues of research into the disease.
Other genes, including LYN and BLK, also appear to be involved in Lupus. These genes affect the function of B cells, which play a key role in the production of antibodies. Autoantibodies, which attack the body's own proteins, contribute to the damage done to the body in Lupus.
The new research also confirms links identified in previous studies between Lupus, as well as other autoimmune diseases, and certain other genes.
Professor Timothy Vyse, a Wellcome Trust Senior Fellow from the Division of Medicine at Imperial College London, and one of the authors of the study, said: "Lupus is a complex disease, which is hard to diagnose, and it can cause many different and unpredictable problems for patients. Living with Lupus can be really tough. We currently can treat the disease by suppressing the immune system, but we urgently need to understand in much more detail what goes wrong with the immune system so that we can design better treatments. This study represents a milestone in progress towards unravelling the secrets of the disease.
"We are continuing to work on refining these genetic studies. Blood samples from patients with Lupus have helped us already and we are very grateful to those who have given us samples. We always need more samples and would like to hear from anyone with Lupus who would like to help us by giving blood samples for this important research," added Professor Vyse.
The researchers reached their conclusions after comparing the genetic makeup of 720 women of European descent with Lupus and 2,337 women without Lupus. They looked at mutations in the building blocks, called nucleotides, which make up DNA.
There are mutations in around one in every 600 nucleotides and the scientists examined over 317,000 how many of these mutations to find those specific to Lupus. These mutations are known as single-nucleotide polymorphisms.
The researchers confirmed their results by comparing another set of genetic data for 1,846 women with Lupus and 1,825 women without Lupus.
The study was carried out by researchers in the International SLE consortium (SLEGEN), which includes scientists from the USA, Sweden and the UK. It was supported by the Alliance for Lupus Research and the National Institutes of Health.
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