Developing disease definitions and biomarkers
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Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) often overlap. While there have been some therapeutic advances, significant needs remain around diagnosis and monitoring, with a gap around definitions and biomarkers for refractory disease or specific subsets. EULAR – The European Alliance of Associations for Rheumatology – held its 2026 annual Congress in London, where new data showcased advances in the field.

Severe refractory systemic lupus erythematosus (srSLE) is a clinical state conceptualised as persistent high disease activity despite standard care with glucocorticoids and immunosuppressants. But no operational definition is widely accepted, limiting trial eligibility, outcome benchmarking, and evaluation for novel therapies. A pilot definition of srSLE based on high disease activity plus concurrent exposure to glucocorticoids and immunosuppressive on two consecutive visits has been shown to be associated with adverse outcomes.1 At the EULAR 2026 Congress in London, a group evaluated 80 candidate definitions for srSLE, aiming to combine disease activity and treatment exposure in order to identify an optimal working definition that could identify patients most likely to benefit from intensive treatments and immune-reset therapies.

Data were analysed from 4,106 patients and 42,355 visits. Adverse outcomes included were flare, damage accrual, and failure to attain lupus low disease activity score (LLDAS) – alongside various thresholds of disease activity and treatment combinations. The proportions attaining the definitions varied from 2% to 27% for the most to least stringent candidates. Ten definitions associated with the highest 12-month rates of the three adverse outcomes were further assessed using machine-based prediction models. One definition was flagged as having the best predictive performance: this was the presence of a score of 6 of more on the SLE disease activity index plus PGA greater than 1, mild-to-moderate or severe flare, and receiving at least 10 mg/day of glucocorticoid.

Presenting the work, Rangi Kandane-Rathnayake said “We have derived a short list of pragmatic, data-driven, and operational definitions of srSLE based on strong associations with adverse outcomes. These show strong predictive performance, and could be used in screening to enrich for patients at highest 12-month risk. If validated in independent cohorts, this has the potential to standardise patient selection for novel intensive therapy studies and support regulatory evaluations.”

In another oral looking at prediction in SLE, Junjie Peng explored whether novel serum autoantibody signatures can predict atherosclerosis progression and response to atorvastatin in children and young people with juvenile-onset systemic lupus erythematosus (JSLE) – where cardiovascular disease is a leading cause of morbidity and mortality.

A biomarker discovery study was conducted using baseline serum samples from 94 participants in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, where carotid intima-media thickness progression (CIMT) was the primary outcome.2 Analysis identified high and low CIMT progression groups in both trial arms. Across all baseline serum samples, 579 autoantibodies were identified as true signals. In the placebo arm, six autoantibodies (STK24, RAD23B, HDAC4, STAT4, SEPTIN9 and NFIA) were significantly associated with high versus low CIMT progression. In contrast, a distinct autoantibody profile was identified in the atorvastatin arm, with ABI1, ATP5B, CSNK2A2, NRIP3, PRKAR1A, PDK4, BATF and NUDT2 significantly associated with CIMT progression despite atorvastatin therapy. A closer look at the autoantibody signature suggested lipid-independent mechanisms could contribute to persistent atherosclerosis progression in statin-treated patients. Based on the predictive models generated, the authors propose a two-step stratification strategy using baseline autoantibody profiling to identify individuals at high risk of atherosclerosis progression, and those unlikely to respond to a statin, enabling precision-guided cardiovascular risk management in JSLE.

In other new data shared at the EULAR 2026 Congress, Haiyue Jiang showcased a novel pathogenic autoantibody in seronegative antiphospholipid syndrome (SN-APS). The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test.3 But there is a subset of patients with classic clinical APS manifestations despite testing negative for lupus anticoagulant, andanticardiolipin (aCL) and anti-β2-glycoprotein I (anti-β2GPI) antibodies – although the immunological basis remains unexplored. The group used a high-density human proteome microarray of 20,000 proteins to screen candidate autoantigens and novel serological markers, and then constructed a targeted protein microarray for validation.

Myosin Va (MYO5A) was identified as a candidate autoantigen, and subsequently validated. Serum anti-MYO5A levels were significantly elevated in patients with APS or SN-APS compared with controls and healthy donors, and were independently associated with an increased risk of thrombotic events. In two in vivo models looking at thrombosis and muscle injury, administration of anti-MYO5A significantly shortened the time to carotid thrombus formation, and promoted microvascular thrombosis in muscle. These findings expand the serological spectrum of APS and provide new mechanistic insights into its immunopathogenesis, and this novel autoantibody could have potential diagnostic value in the future.

Source

Kandane-Rathnayake R, et al. Evaluation of Candidate Definitions of Severe Refractory Systemic Lupus Erythematosus Using Clinical Outcomes: Real-World Data Exploration Study. Presented at EULAR 2026; OP0218. Ann Rheum Dis 2026; DOI: 10.1136/annrheumdis-2026-eular.B.1881.

Peng J, et al. Autoantibody Signatures for Risk Stratification of Atherosclerosis Progression and Statin Response in Juvenile-Onset Systemic Lupus Erythematosus. Presented at EULAR 2026; OP0150. Ann Rheum Dis 2026; DOI: 10.1136/annrheumdis-2026-eular.A.670.

Jiang H, et al. Anti-Myosin Va Antibodies: A Novel Pathogenic Autoantibody in Antiphospholipid Syndrome. Presented at EULAR 2026; OP0297. Ann Rheum Dis 2026; DOI: 10.1136/annrheumdis-2026-eular.A.334.

References

1. Kandane-Rathnayake R, et al. Prevalence and outcomes of a pilot definition of severe refractory systemic lupus erythematosus: observations from a multinational Asia-Pacific cohort. Arthritis Res Ther 2025;27(1):155. DOI: 10.1186/s13075-025-03622-8.

2. Schanberg LE, et al. Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort. Arthritis Rheum 2009;60(5):1496–507. DOI: 10.1002/art.24469.

3. Barbhaiya M, et al. 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Arthritis Rheumatol 2023;75(10):1687–702. DOI: 10.1002/art.42624.

About EULAR

EULAR is the European umbrella organisation representing scientific societies, health professional associations and organisations for people with rheumatic and musculoskeletal diseases (RMDs). EULAR aims to reduce the impact of RMDs on individuals and society, as well as improve RMD treatments, prevention, and rehabilitation. To this end, EULAR fosters excellence in rheumatology education and research, promotes the translation of research advances into daily care, and advocates for the recognition of the needs of those living with RMDs by EU institutions.

Contact

EULAR Communications, communications@eular.org