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Scientists have created the most comprehensive map of the blood proteome in systemic lupus erythematosus (SLE or ‘lupus’) to date. The findings uncover potential biomarkers that could offer targets for new treatments.

In this study , researchers identified distinct molecular patterns that could help tailor treatments to individual patients in clinic by measuring thousands of proteins in patient blood samples. This research is the result of a collaboration between scientists from the Department of Immunology and Inflammation and Imperial College Healthcare NHS Trust Lupus Centre clinicians.

Systemic lupus erythematosus or SLE is an autoimmune disease where the body’s immune system attacks its own tissue and organs. It is a long-term condition where symptoms can range from mild to severe and affect many parts of the body, , particularly the kidneys. In SLE, this happens because of malfunctioning immune proteins in the blood, which attack the body's own healthy cells. These proteins are called autoantibodies and can test positive for a specific type of these proteins called anti-nuclear antibodies (ANA) through an ANA test. Because of the variability of SLE, treatments are difficult to develop and evaluate, and there is an urgent need for further research in this area.

In this research, scientists analysed blood plasma from 260 patients with SLE alongside 86 healthy volunteers using the latest cutting-edge protein analysis technology.

Dr James Peters, Clinical Associate Professor in Rheumatology in the Department of Immunology and Inflammation, said: “The heterogeneity of lupus presents challenges for drug target identification and for clinical trials. We chose to study proteins as these are the targets of nearly all drugs.

“Our study is the largest of its kind in lupus, both in terms of breadth of proteins measured and the number of participants. We found that patients with different autoantibodies have distinct protein profiles, suggesting that a single treatment approach is unlikely to work for everyone. Our findings start to reveal the molecular basis for the clinical heterogeneity seen in lupus, and point the way to precision medicine strategies.”

A molecular map of lupus

A universal feature of lupus is the presence of autoantibodies directed against the contents of the cell nucleus called anti-nuclear antibodies. However, the specific targets of these autoantibodies vary between patients. A key finding from this study was the identification of subgroups of patients with distinct protein profiles linked to the specific autoantibodies that patients had.

For example, patients with anti-double-stranded DNA (dsDNA) antibodies had higher levels of an immune signalling protein called CD40L, and CD40L levels closely tracked disease activity in this group. This relationship was not seen in patients without dsDNA antibodies. This could have important therapeutic implications. Drugs targeting CD40L are already in early phase development. This study’s findings suggest trials of these drugs should focus on patients with dsDNA antibodies to maximise the chances of success of these agents.

Implications for precision medicine

The findings highlight the potential for protein profiling to help guide a more personalised approach to lupus treatment. By identifying the molecular pathways most active in particular subgroups of patients, the scientists suggest that it may be possible to match patients to the therapies more effectively.

The researchers caution that further research is needed to track how these signatures change over time and how they are impacted by treatment.

This work is supported by the NIHR Imperial Biomedical Research Centre, a translational research partnership between ÌìÃÀ´«Ã½ and Imperial College Healthcare NHS Trust.

‘Mapping the plasma proteomic architecture of systemic lupus erythematosus’ by Leung, G. H., Bottomley, C., Buang, N., Maughan, R. T., Whittle, B. J., Zeidaabadi, B., et al. is published in JCI Insight. DOI: