Background: The role of neutrophils in the pathogenesis of Granulomatosis with polyangiitis (GPA) and Microscopic polyangiitis (MPA) is well established [1]. Whether the pattern of neutrophil activation differs between patients with newly diagnosed and relapsing disease is unclear.

Objectives: We sought to analyze the transcriptome of GPA/MPA patients with active disease or remission and investigate their molecular classification.

Methods: We conducted next-generation sequencing (101 bp single-end RNA-sequencing, NovaSeq6000-seq Illumina platform) in whole blood of patients with active GPA/MPA either at diagnosis (n=6), relapse (n=5) or remission (n=10; on Rituximab-maintenance therapy: n=4, off therapy: n=6) and age-/sex-matched healthy controls (n=12). None of patients with active disease received immunosuppressive therapy at the time of sampling. Sequences were aligned to the human genome (hg19; HISAT2 program); gene-expression quantification was performed by HTSeq and differential expression analysis was conducted using DESeq2, with FDR <0.05, log ₂ FC<-1.5 and log ₂ FC>1.5. Gene ontology analysis was performed using the EnrichR webtool.

Results: Over-presentation analysis in relapsed compared to newly diagnosed patients with active GPA/MPA revealed upregulated molecular pathways relevant to neutrophil degranulation, neutrophil extracellular trap formation and antigen presentation. As a result, we discovered a unique gene signature comprised of 29 neutrophil-associated differentially expressed genes (Figure 1), which can distinguish relapsed patients from patients at diagnosis, remission and healthy controls.

Conclusion: There are clear differences in the neutrophil transcriptional reprogramming between newly diagnosed GPA/MPA patients compared to patients with relapsing disease. These findings could have implications in the better understanding of disease pathogenesis and treatment approaches.

Figure 1.

Heatmap of neutrophil-associated DEGs in GPA/MPA patients with active disease (newly diagnosed or relapsed) or remission (on or off therapy) and in healthy controls. RTX; Rituximab, DEGs; differentially expressed genes.

REFERENCES: [1] Prendecki M, Gurung A, Pisacano N, Pusey CD. The role of neutrophils in ANCA-associated vasculitis. Immunol Lett. 2024;270:106933.

Acknowledgements: This work was supported in part by the Special Account for Research Grants, National and Kapodistrian University of Athens, Athens, Greece (DV #12085, 12086) and by the Greek Rheumatology Society and the Greek Association of Professional Rheumatologists (ERE-EPERE).

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.