Serum IgA autoantibody profiling in systemic lupus erythematosus reveals associations with disease phenotypes.

BACKGROUND

Knowledge of the role of IgA isotype autoantibodies in systemic lupus erythematosus (SLE) is lacking. We aimed to explore associations between serum IgA autoantibody profiles and SLE clinical phenotypes using an unbiased approach.

METHODS

1613 serum IgA autoantibodies were quantified in 60 patients with SLE using the i-Ome protein array, customised to also detect antibodies against three interferons (IFNα1, IFNω and IFNγ). Using clustering analysis, patients were grouped according to IgA autoantibody profiles; associations between clusters and clinical features were assessed using multinomial logistic regression. Associations between individual autoantibodies and clinical features were assessed via differential abundance analysis and supervised learning.

RESULTS

Five patient clusters were identified; patients in cluster 4, characterised by antitransforming acidic coiled-coil-containing protein 1 (anti-TACC1) and anti-cAMP-dependent protein kinase type I-alpha regulatory subunit (anti-PRKAR1A) IgA profiles, were significantly more likely to be of Asian ethnicity and have lupus nephritis than those in clusters 1 and 3. Patients in cluster 4 and those in cluster 3, characterised by antiangiomotin-like protein 2 (anti-AMOTL2) IgA profiles, were significantly more likely to use immunosuppression than those in cluster 2. Analysis of individual autoantibodies revealed a significant association between antisignal transducing adaptor molecule 2 (anti-STAM2) and haematological disease activity. Targeted analysis demonstrated associations between several autoantibodies to IFN-associated proteins and SLE phenotypes, including ethnicity, disease activity, immunosuppression and organ damage.

CONCLUSIONS

Clustering according to IgA autoantibody profiles suggests the presence of a subgroup of patients with SLE associated with Asian ethnicity, lupus nephritis and immunosuppression use. Additionally, a novel association between anti-STAM2 IgA and haematological disease was discovered. These findings demonstrate the pathophysiological relevance of IgA autoantibodies in SLE and suggest their potential as SLE biomarkers.