Baseline Multiome Sequencing of CD45RO+CD45RA-CD4+ T Cell Reveals Distinct Immune Profiles Associated with Subsequent Response to Secukinumab Treatment

Addison Pacheco¹, Zoya Qaiyum², Fataneh Tavasolian³, Melissa Lim⁴, Michael Tang¹ and Robert Inman¹, ¹University Health Network, Toronto, ON, Canada, ²Krembil Research Institute, Toronto, ON, Canada, ³Krembil Research Institute - the University Health Network, Toronto, ON, Canada, ⁴University of Toronto, Toronto, ON, Canada

Meeting: ACR Convergence 2024

Keywords: Ankylosing spondylitis (AS), Cytotoxic Cells, interferon, T Cell, T-Lymphocyte

Session Information

Date: Monday, November 18, 2024

Title: T Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: Our study aims to discriminate immune profiles between secukinumab responders (SEC-R) and nonresponders (SEC-NR) in axial spondyloarthritis (axSpA) patients before biologic treatment.

Methods: CD45RO+CD45RA-CD4+ T cells from 2 healthy controls, 3 SEC-R and 3 SEC-NR patients were FACS sorted and 10000 nuclei per sample were collected for Multiome Sequencing. Frequency of CD4+ T cell subsets were compared between SEC-R and SEC-NR using flow cytometry.

Results: SEC-NR patients demonstrate increased transcripts for IL-26, ROR2, and GPR15 and decreased GZMB and GNLY transcripts compared to SEC-R patients. 19 unique CD45RO+CD45RA- CD4+ T cell clusters were revealed and were grouped into central memory, effector, regulatory or cytotoxic subsets. SEC-NR patients demonstrated decreased proportion of central memory and regulatory clusters compared to SEC-R patients. SEC-NR patients had an increased proportion of T-helper 1 cells with high IFNG antisense RNA 1 (IFNG-AS1) expression and without cytotoxic potential. SEC-NR patients had a significant increase of CXCR3+ CD4+ T cells pre-secukinumab compared to SEC-R patients (mean difference = 4.4%, p< 0.01). SEC-R patients represented an increased proportion of cytotoxic CD4+ T cells pre-biologic compared to SEC-NR patients. Flow cytometry revealed GZMA+ CD4+ T cells frequency was increased in SEC-R patients compared to SEC-NR patients pre-secukinumab (mean difference=4.5%, p< 0.05).

Conclusion: Before secukinumab treatment, a different CD45RO+CD4+ T cell immune profile is present between patients subsequently proved to be SEC-R vs SEC-NR. SEC-NR patients demonstrate the potential for enhanced IFN-g production while SEC-R patients demonstrate greater cytotoxic potential in their T-helper 1 cell subset. The results point toward more immune heterogeneity in axSpA than has been recognized and highlights the need for precision therapeutics in this disease.

Disclosures: A. Pacheco: None; Z. Qaiyum: None; F. Tavasolian: None; M. Lim: None; M. Tang: None; R. Inman: Abbvie, 2, Janssen, 2, novartis, 2, 5, UCB, 2.

To cite this abstract in AMA style:

Pacheco A, Qaiyum Z, Tavasolian F, Lim M, Tang M, Inman R. Baseline Multiome Sequencing of CD45RO+CD45RA-CD4+ T Cell Reveals Distinct Immune Profiles Associated with Subsequent Response to Secukinumab Treatment [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/baseline-multiome-sequencing-of-cd45rocd45ra-cd4-t-cell-reveals-distinct-immune-profiles-associated-with-subsequent-response-to-secukinumab-treatment/. Accessed .

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