P090 Low-density neutrophils are higher in individuals with active ulcerative colitis

Mendieta Escalante, E.A.(1)*;Dijkstra, G.(1);Faber, K.N.(1);Yamamoto Furusho, J.K.(2);Barrera-Vargas, A.(3);Torres-Ruiz, J.J.(4);Merayo-Chalico, F.(3);

(1)University Medical Center of Groningen, Gastroenterology and Hepatology, Groningen, The Netherlands;(2)National Institute of Medical Sciences and Nutrition Salvador Zubirán, Inflammatory Bowel Disease Clinic, Mexico City, Mexico;(3)National Institute of Medical Sciences and Nutrition Salvador Zubirán, Rheumatology, Mexico City, The Netherlands;(4)National Institute of Medical Sciences and Nutrition Salvador Zubirán, Rheumatology, Mexico City, Mexico;

Background

Introduction: Neutrophils and neutrophil extracellular traps (NETs) play a significant role in the pathogenesis of ulcerative colitis (UC), a chronic and relapsing inflammatory disease of the colon.  Low-density neutrophils (LDNs) are a recently identified subset of neutrophils that are more prone to develop NETs and produce more pro-inflammatory cytokines and calprotectin than neutrophils of normal density. Moreover, LDNs show reduced phagocytotic activity towards bacteria. LDNs are subclassified as mature (CD15+CD14-CD10+) and immature (CD15+CD14-CD10-) based on CD10 expression, of which the immature LDNs are most pro-inflammatory. LDNs have been identified in a number of autoimmune diseases, including systemic lupus erythematosus, psoriasis, antineutrophil cytoplasmic antibody-associated vasculitis, and rheumatoid arthritis, but not yet studied in UC.
Objective: Examine the existence of LDNs in UC patients and their possible association to disease severity.

Methods

A total of 13 healthy controls and 20 patients with UC were included. Their clinical activity was evaluated with the Truelove-Witts score. LDNs and subtypes were quantified by flow cytometry in the peripheral blood mononuclear cells (PBMC).

Results

The relative abundance of LDNs was significantly higher in UC patients compared to healthy controls (1.55±1.14 vs. 0.62±0.36 respectively, P<0.05). Moreover,  LDNs numbers were higher in UC patients with active disease compared to those in remission (2.67±1.36 vs. 1.09±0.55; P<0.05) (Figure 1). The abundance of immature (CD15+CD14-CD10-) LDNs positively correlated with the Truelove-Witts index (rho=.530, P<0.05) and fecal calprotectin levels (OR=1.2, P<0.05, CI=1-1.36) as illustrated in Figure 2.

Figure 1
Figure 1
Figure 2
Figure 2

Conclusion

LDNs levels are elevated in PBMCs of patients with UC and pro-inflammatory immature LDNs are associated with disease activity.