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Abstract Number: 1665

Longitudinal Stratification of Gene Expression Reveals Three SLE Groups of Disease Activity Progression

Daniel Toro1, Jordi Martorell-Marugán2, Daniel Goldman3, Michelle Petri4, Pedro Carmona Sanz5 and Marta Alarcón-Riquelme6,7, 1Bioinformatics and Medical Genomics, Center for Genomics and Oncological Research (GENYO), Pfizer-University of Granada-Andalusian Regional Government, Health Sciences Technology Park, Ganada, Spain, 2Bioinformatics Unit, Center for Genomics and Oncological Research (GENYO), Granada, Spain, 3Medicine (Rheumatology), Johns Hopkins University School of Medicine, Baltimore, MD, 4Johns Hopkins University School of Medicine, Baltimore, MD, 5Unit of Bioinformatics, Center for Genomics and Oncological Research (GENYO), Pfizer-University of Granada-Andalusian Regional Government, Health Sciences Technology Park, Granada, Spain, 6Unit for Chronic Inflammatory Diseases, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 7Center for Genomics and Oncological Research (GENYO), Pfizer-University of Granada-Andalusian Regional Government, Health Sciences Technology Park, Granada, Spain

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Disease Activity, Gene Expression, Lupus and nephritis

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Session Information

Date: Monday, October 22, 2018

Title: Systemic Lupus Erythematosus – Clinical Poster II: Biomarkers and Outcomes

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: The highly heterogeneous clinical presentation of lupus is characterized by the unpredictable appearance of flares of disease activity and important organ damage. Attempts to stratify lupus patients have been limited to clinical information, leading to unsuccessful clinical trials and controversial research results. Our aim was to develop and validate a robust method to stratify patients with lupus according to longitudinal disease activity and whole-genome gene expression data in order to establish subgroups of patients who share disease progression mechanisms.

Methods: We applied a clustering-based approach to stratify SLE patients based on the correlation between disease activity scores and longitudinal gene expression information. Clustering robustness was evaluated by bootstrapping and the clusters were characterized in terms of clinical and functional features.

Results: Using two independent sets of patients, one pediatric and another adult, our results show a clear partition into three different disease clusters not influenced by treatment, race or other source of bias. Two of the clusters differentiate into a neutrophil correlated disease group and a lymphocyte correlated disease group, while the third that correlated to a lesser extent with neutrophils, was functionally more heterogeneous. The neutrophil-driven clusters were associated with increased development towards proliferative nephritis.

Conclusion: We found three subgroups of patients that show different mechanisms of disease progression and are clinically differentiated. Our results have important implications for treatment options, the design of clinical trials, the etiology of the disease, and the prediction of severe glomerulonephritis.


Disclosure: D. Toro, None; J. Martorell-Marugán, None; D. Goldman, Merck & Co., Pfizer, 1; M. Petri, None; P. Carmona Sanz, None; M. Alarcón-Riquelme, Sanofi, Bayer, UCB, Eli Lilly and Servier, 2.

To cite this abstract in AMA style:

Toro D, Martorell-Marugán J, Goldman D, Petri M, Carmona Sanz P, Alarcón-Riquelme M. Longitudinal Stratification of Gene Expression Reveals Three SLE Groups of Disease Activity Progression [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/longitudinal-stratification-of-gene-expression-reveals-three-sle-groups-of-disease-activity-progression/. Accessed .
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