ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0523

Distinct Peripheral Blood Immune Cell Sub-population Signatures at Baseline of Tofacitinib or Adalimumab Initiation Are Associated to Clinical Responses at 6 Months

Panagiota Goutakoli1, Eirini Sevdali1, Elpida Neofotistou-Themeli1, Argyro Repa2, Nestor Avgoustidis3, Sofia Pitsigavdaki4, Eleni Kalogiannaki2, George Bertsias5, Nikolaos Paschalidis6, Panayotis Verginis7 and Prodromos Sidiropoulos8, 1University of Crete, Laboratory of Rheumatology, Autoimmunity and Inflammation, Heraklion, Greece, 2University Hospital, Rheumatology, Clinical Immunology, Heraklion, Greece, 3University Hospital, Rheumatology and Clinical Immunology,, Heraklion, Greece, 4Rheumatology and Clinical Immunology, University of Crete School of Medicine, Heraklion, Greece, Heraklion, Greece, 5Laboratory of Rheumatology, Autoimmunity and Inflammation. University Hospital, Rheumatology, Clinical Immunology, Heraklion, Greece, 6Biomedical Research Foundation, Academy of Athens, Athens, Greece, 7Medical School, University of Crete, Heraklion, Crete, Greece, 8University of Crete, Laboratory of Rheumatology, Autoimmunity and Inflammation. University Hospital, Rheumatology, Clinical Immunology. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Heraklion, Greece, HERAKLIO, Greece

Meeting: ACR Convergence 2024

Keywords: , , ,

Session Information

Date: Saturday, November 16, 2024

Title: RA – Treatment Poster I

Session Type: Poster Session A

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

Background/Purpose: Biomarkers to predict response to tofacitinib or adalimumab are not clinically available. Herein we aimed to characterize peripheral blood immune cell subsets with a specific focus in JAK-STAT pathway, associated to clinical responses in patients with rheumatoid arthritis (RA) starting targeted therapies.

Methods: This is a prospective single center study of RA patients starting tofacitinib or adalimumab as the first targeted therapy. Response to therapy based on DAS28 was assessed at 6 months. Patients on remission or low disease activity were classified as responders, the rest as non-responders. We applied mass cytometry (Cytometry by time-of-flight, CyTOF) to analyze peripheral blood mononuclear cells (PBMCs) for identifying cellular biomarkers predictive of response to the aforementioned treatments. PBMCs analyzed were collected at baseline, prior to treatment initiation. Cells were stained with a comprehensive multiplex antibody panel that included extracellular markers for distinguishing key immune cell populations such as T helper cells, T cytotoxic cells, T regulatory cells, B cells, NK cells, and myeloid cells. Additionally, markers for phosphoproteins, such as pS6, pERK, pSTAT1, and pSTAT3, were incorporated. This approach aims to elucidate cellular mechanisms underlying treatment response and identify potential biomarkers for therapeutic efficacy.

Results: Out of 110 patients recruited, 46 completed 6 months of follow-up and had a complete dataset. 13/24 patients on tofacitinib and 11/22 on adalimumab responded at 6 months. A preliminary analysis of baseline cell subpopulations associated to clinical responses, showed that CD11c+CD113+CD86+ plasmacytoid dendritic cells were increased in “tofa-responders” vs non-responders, while CD56+CD25- natural killer cells were over-represented in “tofa-non-responders” vs responders. An increased CD56+CD16+pSTAT3low cell population was specifically associated to response to adalimumab. Interestingly, within the T-cell compartment, a CD8a+CD25+HLADR-Foxp3lowpERK1/2+pSTAT1+ cell population was increased in “ada-responders” as compared to non-responders.

Conclusion: In this preliminary analysis, a distinct peripheral blood immune-cell sub-population signature between tofacitinib and adalimumab was associated to clinical response to these targeted agents. We will further analyze JAK-STAT activation status in immune cells as well as a serum proteomic analysis will be performed to better characterize a clinically applicable biomarker to predict response to the above targeted therapies. 

Disclosures: P. Goutakoli: None; E. Sevdali: None; E. Neofotistou-Themeli: None; A. Repa: None; N. Avgoustidis: None; S. Pitsigavdaki: None; E. Kalogiannaki: None; G. Bertsias: None; N. Paschalidis: None; P. Verginis: None; P. Sidiropoulos: None.

To cite this abstract in AMA style:

Goutakoli P, Sevdali E, Neofotistou-Themeli E, Repa A, Avgoustidis N, Pitsigavdaki S, Kalogiannaki E, Bertsias G, Paschalidis N, Verginis P, Sidiropoulos P. Distinct Peripheral Blood Immune Cell Sub-population Signatures at Baseline of Tofacitinib or Adalimumab Initiation Are Associated to Clinical Responses at 6 Months [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/distinct-peripheral-blood-immune-cell-sub-population-signatures-at-baseline-of-tofacitinib-or-adalimumab-initiation-are-associated-to-clinical-responses-at-6-months/. Accessed .

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