Summary
A bioRxiv preprint reports anti-SDMA autoantibodies in 30–40% of people with systemic lupus erythematosus. In a separate validation cohort of 201 patients, antibody levels correlated with disease-activity scores and complement levels.
A bioRxiv preprint reports that 30–40% of people with systemic lupus erythematosus (SLE) have autoantibodies that recognise symmetric dimethylarginine (SDMA), a chemical modification of the amino acid arginine in proteins. In a validation cohort of 201 patients, the researchers found that anti-SDMA antibody levels tracked with measures of lupus activity and complement levels. The findings point to a shared chemical feature that may help explain some of the variety in lupus antibody responses.
How the researchers traced antibody recognition
The team used methylome-wide peptide arrays to identify antibodies that bind SDMA-modified peptides. Antibodies are immune proteins that bind particular molecular features; chemical modifications can change those features and create targets the immune system recognises. The researchers report that patients had individual patterns of recognition, even though anti-SDMA responses were found across a substantial share of the group.
Experiments with a monoclonal antibody from MRL-lpr mice found that it recognised multiple SDMA-modified antigens. The researchers also found that Epstein-Barr virus protein EBNA-1 bound plasma from people with SLE in an SDMA-dependent manner. They suggest this could reflect molecular mimicry: immune recognition of a shared feature in viral and self proteins. The result raises a possible connection, but does not establish that EBNA-1 triggers lupus.
Antibody levels tracked with clinical measures
In the 201-patient validation cohort, anti-SDMA titres correlated with SLEDAI-2K scores, a measure of lupus disease activity, and were inversely correlated with C3 and C4, proteins in the complement system. Seropositivity was also more common among younger patients, people with renal involvement and those with anti-Sm antibodies.
These are associations: they connect anti-SDMA responses with clinical features, but do not show that the antibodies cause disease activity or kidney involvement. The study is a preprint, and its findings describe a possible marker and immune-recognition pattern rather than an established clinical test. Whether SDMA-directed antibodies contribute to lupus biology remains an open research question.