Neutrophil extracellular traps and inflammatory response: Implications for the immunopathogenesis of ankylosing spondylitis

Abstract

Aim Ankylosing spondylitis (AS) pathogenesis has focused on the adaptive immune response; however, innate immune responses may also play a role in the inflammatory response of AS. Dysregulated neutrophil activation can induce tissue damage and contribute to the pathogenesis of immune‐related diseases. Hence, the aim of this study was to assess the effect of immune complexes formed with the p30 of Salmonella typhimurium and anti‐p30 antibodies present in the sera of AS patients and controls in inducing the release of neutrophil extracellular traps (NETs) and the secretion of pro‐inflammatory cytokines. Methods We collected polymorphonuclear leukocytes (PMNs) from healthy donors. The PMNs isolated were stimulated with p30 alone or in immunocomplexes formed with antibodies presents in sera of AS patients or control subjects. Then, the NETs were analyzed by fluorescence microscopy. Concentrations of interleukin (IL)‐6, tumor necrosis factor (TNF)‐α, IL‐1β, IL‐8 and IL‐10, were determined using the Cytometric Bead Array kit. Results Significant difference was observed in the release of NETs between the neutrophils stimulated with p30 + AS (70.52 ± 16.24) those unstimulated neutrophils (9.94 ± 12.12; P = .0095), stimulated with phorbol 12‐myristate 13‐acetate (39.78 ± 14.50; P = .0190), stimulated with control serum (CS) (10.85 ± 5.33; P = .0082) and serum of AS patient (10.28 ± 6.15; P = .0087). The stimulation of neutrophils with p30 alone induced a relatively low production of IL‐6 (64.5 pg/mL), IL‐8 (2658.3 pg/mL), IL‐1β (31.11 pg/mL), and TNF‐α (3.8 pg/mL), compared to p30 + AS and p30 + CS groups. Conclusion Our results show that neutrophils release NETs and pro‐inflammatory cytokines in response to p30 in immunocomplexes. These findings could improve our understanding of the role of innate immunity in the initiation and/or maintenance of inflammatory responses, and in the progression of AS.

Exploring causal correlations between inflammatory cytokines and ankylosing spondylitis: a bidirectional mendelian-randomization study

“…Moreover, our findings suggest a reciprocal causation between TRAIL and AS. In AS, IL-1β is also considered a critical pro-inflammatory cytokine, and its expression levels may be upregulated, similar to findings by Zambrano-Zaragoza and Peng ( 32 , 33 ), who observed elevated IL-1β levels in AS patients. However, this does not necessarily imply that IL-1β can cause AS; it could also be a negative feedback regulation by the body to protect itself.…”

Application of neutrophil to lymphocyte ratio in ankylosing spondylitis: Based on bibliometric and visualization analysis

“…Furthermore, it can serve as a marker for systemic rheumatism, as indicated by recent research. [38][39][40] Meacan et al [41] found that an increase in neutrophil count is generally associated with poor prognosis and increased mortality. A clinical metaanalysis study also showed that NLR is a reasonable measure for detecting systemic inflammation in AS patients and can indicate disease activity in AS patients.…”

Immune mechanism of low bone mineral density caused by ankylosing spondylitis based on bioinformatics and machine learning

“…NETs can act as an autoantigen to coordinate congenital and adaptive immune disorders, participate in the self-magnifying cycle of autoimmune inflammation, and produce cell and tissue-specific damage in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus (Fousert et al, 2020;Goel and Kaplan, 2020). Similarly, NETs production increased in AS and was associated with AS inflammation and activity (Ruiz-Limon et al, 2018;Zambrano-Zaragoza et al, 2021).…”