Autoantibody Profiles Shown to Predict High Risk for SLE

Serum samples of patients who later develop systemic lupus erythematous (SLE) demonstrated SLE-like autoantibody profiles prior to diagnosis, which may be helpful in identifying patients at high risk of developing SLE, according to study results published in Human Immunology.

To further examine autoantibodies that could precede the first clinical manifestations of SLE and identify patients at risk for SLE, the researchers used a custom-made antibody microarray containing 57 autoantigens to analyze serum samples of participants who were previously tested for anti-dsDNA and samples of self-reported healthy blood bank donors (BBD).

Of the 1519 study participants, 483 had SLE, 346 participants had another immune-mediated inflammatory disease (IMID), 218 control participants did not have relevant clinical symptoms, such as arthritis, nephritis or pleuritis (non-IMID), and 472 participants did not fit into the previous groups.

The IMIDs other than SLE included antiphospholipid syndrome (APS), cutaneous lupus erythematosus (CLE), giant cell arteritis (GCA), juvenile idiopathic arthritis (JIA), lupus-like disease (LLD; also known as ‘‘incomplete lupus), mixed connective tissue disease (MCTD), polymyositis, dermatomyositis, polymyalgia rheumatica (PMR), Sjögren syndrome, rheumatoid arthritis (RA), systemic sclerosis (SSc), and undifferentiated connective tissue disease (UCTD).

Researchers identified 17 pre-SLE samples, which was confirmed if a participant received a diagnosis of SLE in later samples during follow-up, received a diagnosis of SLE up to 2 years after the last sampling date, or was identified by their physicians as those who had been cared for a longer period of time but only later received a diagnosis of SLE.

The time between sample date and time of diagnosis varied between 3 weeks and 33 months (mean, 7.2 months). All pre-SLE participants tested positive or had a weak-positive test for antinuclear antibodies (ANA); however, 35% tested positive for anti-dsDNA during sample collection. In participants with SLE, 87% tested positive or had a weak-positive test for ANA and 39% were positive or weak positive for anti-dsDNA at the moment of sample collection.

The non-IMID and BBD groups were used to develop multivariable prediction models of participants who developed SLE during follow-up (pre-SLE). To evaluate the specificity of the non-IMID model, samples from the “rest” group were used as negative controls, though the study authors noted this may limit potential clinical applicability. A stricter cut-off would be more applicable to determining patients at high risk for SLE and who could be kept for follow-up compared with patients at low risk for SLE who could be released from care.

The study was limited by the small number of pre-SLE participants and the short follow-up period.

The study authors concluded, “Further prospective research is needed to confirm the additional diagnostic value of this antibody profile.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Brunekreff TE, Reteig LE, Limper M, et al. Microarray analysis of autoantibodies can identify future systemic lupus erythematosus patients. Human Immunology. Published online April 11, 2022. doi:10.1016/j.humimm.2022.03.010