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Abstract Number: 0351

Gene Signature Fingerprints Divide SLE Patients in Subgroups with Similar Biological Disease Profiles: A Multicenter Longitudinal Study

Javad Wahadat1, Dieneke Schonenberg-Meinema2, Cornelia van Helden-Meeuwsen1, Sander van Tilburg1, Noortje Groot3, Ellen Schatorjé4, Esther Hoppenreijs4, Petra Hissink Muller5, Danielle Brinkman6, Denis Dvorak7, Marleen Verkaaik3, Katerina Bouchalova8, Merlijn van den Berg2, Sylvia Kamphuis9 and Marjan Versnel1, 1Erasmus University Medical Center, Rotterdam, Netherlands, 2Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam, Netherlands, 3Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, Netherlands, 4Amalia Children's Hospital, Nijmegen, Netherlands, 5Willem Alexander Children’s Hospital, Leiden University Medical Center, Leiden, Netherlands, 6Willem Alexander Children’s Hospital, Leiden University Medical Center, Leiderdorp, Netherlands, 7Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital, Olomouc, Czech Republic, 8Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czech Republic, 9Sophia Children’s Hospital, Erasmus University Medical Center, Rotterdam, Netherlands

Meeting: ACR Convergence 2021

Keywords: , ,

Session Information

Date: Saturday, November 6, 2021

Title: SLE – Diagnosis, Manifestations, & Outcomes Poster I: Diagnosis (0323–0356)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: Clinical phenotyping and predicting treatment responses in Systemic Lupus Erythematosus (SLE) patients is challenging. Extensive blood transcriptional profiling has identified various gene modules that seem promising for stratification of SLE patients. This study was undertaken to translate transcriptomic data into gene signatures suitable for introduction into clinical practice and to associate these signatures with disease activity.

Methods: RT-PCR of multiple genes from the Interferon M1.2, Interferon M5.12, neutrophil (NPh)- and plasma cell (PLC) modules followed by a principle component analysis was used to identify indicator genes per gene signature. Gene signatures were measured in longitudinal samples from two childhood onset SLE cohorts (n=101 and n=34, respectively) and associated with clinical features. Disease activity was measured using SELENA-SLEDAI. Cluster analysis subdivided patients into three fingerprint groups termed 1) all-signatures-low, 2) only IFN high (M1.2 and/or M5.12) and 3) high NPh and/or PLC.

Results: All gene signatures were significantly associated with disease activity in cross-sectionally collected samples. The PLC signature showed the highest association with disease activity. Also, in longitudinally collected samples, the PLC signature was associated with disease activity and showed a decrease over time. When patients were divided into fingerprints, the highest disease activity was observed in the high NPh and/or PLC group. The lowest disease activity was observed in the all-signatures-low group. The same distribution could be reproduced in samples from an independent SLE cohort.

Conclusion: Gene signatures are associated with disease activity and can be suitable tools to sub-classify SLE patients into groups with similar pathogenically activated immunological pathways.

Disclosures: J. Wahadat, None; D. Schonenberg-Meinema, None; C. van Helden-Meeuwsen, None; S. van Tilburg, None; N. Groot, None; E. Schatorjé, None; E. Hoppenreijs, None; P. Hissink Muller, None; D. Brinkman, None; D. Dvorak, None; M. Verkaaik, None; K. Bouchalova, None; M. van den Berg, None; S. Kamphuis, GlaxoSmithKline, 7, Aurinia, 2; M. Versnel, None.

To cite this abstract in AMA style:

Wahadat J, Schonenberg-Meinema D, van Helden-Meeuwsen C, van Tilburg S, Groot N, Schatorjé E, Hoppenreijs E, Hissink Muller P, Brinkman D, Dvorak D, Verkaaik M, Bouchalova K, van den Berg M, Kamphuis S, Versnel M. Gene Signature Fingerprints Divide SLE Patients in Subgroups with Similar Biological Disease Profiles: A Multicenter Longitudinal Study [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/gene-signature-fingerprints-divide-sle-patients-in-subgroups-with-similar-biological-disease-profiles-a-multicenter-longitudinal-study/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/gene-signature-fingerprints-divide-sle-patients-in-subgroups-with-similar-biological-disease-profiles-a-multicenter-longitudinal-study/