PRECISESADS

There is currently no treatment for primary Sjögren’s syndrome (pSS), an autoimmune disease that can affect a range of organs and tissues. New findings from IMI’s PRECISESADS project could help to change that.###

In recent years, scientists have run clinical trials of a number of treatments for pSS, but none of these proved successful, and to date there is no approved treatment for pSS. One reason for the clinical trial failures could be the diversity of pSS patients; some treatments may work for certain sub-groups of patients – the challenge is to identify these subgroups and match them up with appropriate treatments.

Now, a new paper in Nature Communications suggests that there could be four sub-groups of pSS patients. The team arrived at this conclusion after drawing up detailed molecular profiles from blood samples from over 300 pSS patients and comparing these with profiles from 330 healthy volunteers. The team also offer suggestions as to which kinds of treatments could work best for the different subgroups, effectively paving the way for more personalised treatments for pSS.

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There is evidence that many autoimmune conditions (such as rheumatoid arthritis, lupus, and Sjögren's syndrome) may share molecular mechanisms. IMI’s PRECISESADS project 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.###

‘We were able to show that these different diseases can be joined together into groups,’ said project coordinator Marta E. Alarcón-Riquelme of the Centre for Genomics and Oncological Research in Granada, Spain. ‘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.

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.

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Affecting around 2 % of the population, autoimmune rheumatic diseases can have severe symptoms, including painful and swollen joints, fever, rashes, fatigue and sensitivity to the sun, with patients needing regular check-ups. ###Diagnosis can take a number of years from the onset of symptoms – too long to prevent negative outcomes. Moreover, wide variations exist between patients in terms of severity, prognosis and response to treatment, which renders therapy a trial-and-error process.

Researchers in IMI’s PRECISESADS project are gathering data on the molecular causes of various autoimmune rheumatic diseases and different patients’ clinical symptoms in order to facilitate the delivery of precision medicine based on earlier and more accurate diagnosis.  ‘Blood samples from over 3 000 patients from across Europe with different autoimmune diseases have undergone in-depth analyses, unprecedented in the field of rheumatology research,’ explains project coordinator John Ioannou of UCB Biopharma in Belgium. ‘Data on genome, transcriptome, proteome, methylome and other biological parameters have been analysed with the identification of novel clusters of molecular signatures, which could form the basis for a brand new classification of these diseases and pave the way towards more tailored therapy.’

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IMI project PRECISESADS has now recruited over 1 000 people into its pan-European clinical study on systemic autoimmune diseases such as rheumatoid arthritis and lupus. The milestone means that the project is well on track to recruit a total of 2 500 people from 9 countries into the study.### In the project, patients with the diseases under study as well as healthy people are giving blood and urine samples which are analysed in detail. ‘This will allow us to gain a full molecular profile of the patients and (hopefully) allow us to cluster the patients into groups based on their molecular profile instead of their clinical symptoms,’ explains project coordinator Marta Alarcón Riquelme of GENYO in Spain. ‘This would then allow clinicians to tailor the therapies to the specific pathways to be targeted in a sort of personalised medicine.’ The project hopes to recruit all patients needed for the study by the middle of 2017.

The work of IMI’s PRECISESADS and AETIONOMY projects on disease taxonomy is spotlighted in a new Nature Reviews Discovery comment piece.### Currently, most diseases are still defined largely on the basis of their symptoms, yet while two patients may share the same diagnosis, the underlying causes of their symptoms may be very different. This means that a treatment that works in one patient may prove ineffective in another. The AETIONOMY and PRECISESADS projects are pioneering a new approach to the classification of disease; for AETIONOMY, in the field of Alzheimer’s and Parkinson’s diseases, and for PRECISESADS, in the field of systemic autoimmune diseases (such as rheumatoid arthritis and lupus). Although the projects are tackling the problem in different ways, their overall goal is the same: to pave the way towards a new taxonomy of disease that is based on the underlying causes of disease. In the long term, this will help to diagnose patients more accurately and provide them with a treatment that works for them.

Join PRECISESADS for a conference on the genomics of complex diseases
IMI’s PRECISESADS will hold a conference on the genomics of conference diseases in Granada, Spain on 10-11 March 2016. PRECISESADS is working on a new classification of autoimmune diseases such as rheumatoid arthritis and lupus, and the study will pave the way for more personalised treatments. ### The conference will provide an overview of the genetic, epigenetic, regulatory and functional aspects of genomics studies as well as the new challenges posed by next generation sequencing and bioinformatics in the understanding of complex diseases, focused on systemic autoimmune diseases. The scientific program will include updates on genetic susceptibility of lupus and other autoimmune diseases, studies around immune cells and autoimmune disease and drug repositioning and other interesting topics. In addition, PhD students and post-docs are invited to submit abstracts for the event. Deadline for registration: 31 December 2015.