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Review
. 2022 Oct 20;3(3):120-127.
doi: 10.2478/rir-2022-0020. eCollection 2022 Oct.

Neutrophils in the Pathogenesis of Rheumatic Diseases

Jia Tong Loh  1 , Kong-Peng Lam  1   2   3
Affiliations
Review

Neutrophils in the Pathogenesis of Rheumatic Diseases

Jia Tong Loh et al. Rheumatol Immunol Res. .

Abstract

Rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), are a group of auto-inflammatory disorders associated with substantial morbidity and mortality. One unifying feature of these diseases is the presence of abnormal neutrophils exhibiting dysregulated neutrophil extracellular trap (NET) release, reactive oxygen species (ROS) production, degranulation, and pro-inflammatory cytokines secretion. Moreover, the release of autoantigens associated with NETs promotes the generation of autoantibodies and a breakdown of self-tolerance, thereby perpetuating inflammation and tissue injury in these patients. In recent years, targeted therapies directed at neutrophilic effector functions have shown promising results in the management of rheumatic diseases. In this review, we will highlight the emerging roles of neutrophils in the onset and progression of rheumatic diseases, and further discuss current and future therapeutic approaches targeting the pathogenic functions of neutrophils, which can modulate inflammation and hence improve patients' survival and quality of life.

Keywords: ANCA-associated vasculitis; neutrophil extracellular traps; neutrophils; rheumatoid arthritis; systemic lupus erythematosus.

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Conflict of interest statement

Conflict of Interest Kong-Peng Lam is an Editorial Board Member of the journal. This article was subject to the journal's standard procedures, with peer review handled independently of this member and his research group.

Figures

Figure 1
Figure 1
Release of NETs by human neutrophils in response to PMA. NETs are identified by DAPI (blue) and citrullinated histone 3 (R2/8/17) (green) staining. Scale bar, 50 μm. NETs, neutrophil extracellular traps. PMA, Phorbol-12-myristate-13-acetate.
Figure 2
Figure 2
Overview of current and future therapies targeting neutrophil functions and survival. Biologics are shown in blue, and small molecule inhibitors are shown in red.
See this image and copyright information in PMC

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