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Proposed ‘clustering’ of patients offers hope for better understanding of autoimmune diseases

PRECISESADS’ findings show that despite being diagnosed with an array of autoimmune diseases, patients can be grouped according to molecular patterns

lupus march
A woman participates in a walk to raise awareness of the autoimmune disorder lupus. Image by Eric Glenn/


There is evidence that many autoimmune conditions may share molecular mechanisms. PRECISESADS carried out painstaking analysis of molecular and clinical data and were able to reclassify around 2,000 individuals affected by systemic autoimmune diseases (SADs) into four different clusters of molecular groupings. By going beyond classical clinical signs and symptoms and grouping people by underlying drivers, the work of the team will help ensure better diagnosis and treatment for people with SADs in the future. 

The project recruited around 2,000 patients who had developed one of a number of autoimmune diseases, including rheumatoid arthritis, lupus, and Sjögren's syndrome, a mean of 12 years previously. They also recruited patients who had been diagnosed in the previous year.

Marta E. Alarcón-Riquelme is Head of medical genomics at the Centre for Genomics and Oncological Research in Granada, Spain, and coordinator of the PRECISESADS project: “I am very interested in systemic autoimmune diseases and in particular the idea that though they share molecular signatures, within each clinical diagnosis, they are very heterogeneous, meaning every patient shows very different clinical characteristics.”

“We wanted to see if there were molecular signatures in blood samples that could tell us something about similarities and differences between these patients,” said Dr Alarcón-Riquelme. They carried out molecular studies on the samples, seeking the number of different types of cells in the samples at a given moment. “The idea was to see whether the signatures that we would find with the one-time cross-sectional study would be very different or would change with time.”

“We took all this data from the DNA and the RNA and looked at how the genes are expressed and also whether there were any particular genetic variants involved."

“We were able to show that these different diseases can be joined together into groups. There were four different groups of patients, formed by all the patients with the different autoimmune diseases. This was new.” The four groups are inflammatory, undefined, lymphoid group and an interferon group. The interferon group was already known for lupus, and it was known that some patients with rheumatoid arthritis or scleroderma could also have the interferon signature.

To go further and build on these new insights, more research is needed. “In another study we would need to look into whether by classifying the patients into in this way, we could actually find which treatment would be best for which patient,” said Dr Alarcón-Riquelme.

A newly-launched IMI project 3TR is focussed on why patients with SADs do not respond to treatment. “We know of course that some people don’t actually take their treatment, that’s a big problem. But putting that aside, we know that many simply do not respond. The clinical studies we will carry out in 3TR will build upon, in part, what we found in PRECISESADS,” said Dr Alarcón-Riquelme.

“We know what happens in tissues is in part reflected in blood. We will be able to see though clinical studies if one of the reasons that they do not respond to a certain treatment is because they do not belong to the molecular group that would have predicted their response to that particular treatment. We will combine blood and tissue molecular patterns to classify the individuals and find the relationship between signatures in blood and those in tissues.”

“Multiple sclerosis is part of 3TR, though it was not included as part of PRECISESADS, so it will be very interesting really to see how they look like when it comes to these groups.”

Read more

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