Background: Studies characterizing systemic lupus erythematosus (SLE) patients have successfully identified homogeneous and clinically actionable SLE subgroups among individuals of White European descent, focusing on the heterogeneous clinical manifestations associated with autoantibody profiles. Validation of these findings across different ethnic populations is essential for their broader application.

Objectives: Therefore, we aimed to subgroup Malay SLE patients based on their autoantibody profiles, addressing the current gap in research concerning non-European populations.

Methods: This cross-sectional study involved 191 Malay SLE patients who met the 2019 EULAR/ACR Classification Criteria. We profiled 15 SLE-associated autoantibodies using immunoblot and ELISA methods. Unsupervised cluster analysis and logistic regression techniques were employed to define autoantibody-based SLE subgroups and explore their association with clinical manifestations.

Results: Our data demonstrated 93% were female with the mean age of 41.14 years (±12.11). We identified four distinct clusters: Cluster 1 (26.18%) was characterized by anti-Ro52 IgG (78%) and anti-SSA IgG (88%) autoantibodies; Cluster 2 (35.08%) by anti-nRNP_sm IgG (68.1%) and anti-Sm (20.9%); Cluster 3 (12.04%) by anti-histone IgG, anti-nucleosome IgG, and anti-nRNP_sm IgG with the prevalent of 91.3% for each autoantibody; and Cluster 4 (26.70%) was autoantibody-negative. Further analysis revealed significantly higher disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K), in Cluster 3 (P _adj < 0.01) compared to Cluster 4; however, there were no significant differences observed between Cluster 3 and the other clusters. Association analysis demonstrated a significant correlation between Cluster 3 and mucocutaneous manifestations, with an odds ratio (OR) of 9.94 (95% CI: 2.29–55.12), as well as renal involvement, with an OR of 6.67 (95% CI: 1.14–54.87).

Conclusion: Our findings align with those observed in White European descendants and further support the application of subgrouping SLE patients based on their autoantibody profiles. These findings warrant future studies to investigate the genetic background of the identified subgroups among clinically heterogeneous SLE patients.

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Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.