Abstract Number: PB1922
Meeting: ISTH 2020 Congress
Theme: Thrombotic Microangiopathies » Antiphospholipid Syndrome
Background: The release of neutrophil extracellular traps (NETs) has been described to be at the basis of immune-mediated thrombosis.
Aims: We investigated whether neutrophil activity and NETs are associated with thrombosis in APS (t-APS).
Methods: 50 secondary t-APS (t-SAPS), 103 primary t-APS (t-PAPS) and 131 individuals without thrombosis (controls) were included. The following markers of NETs were evaluated: gene expressions of PADI4, ELANE, and MPO by qPCR, citrullinated histone H3 (H3cit), circulating levels of myeloperoxidase – DNA complexes (MPO-DNA) and circulating free dsDNA.
Results: Mean age was 37.5 (SD 14.7) in t-SAPS; 42.1 (SD 15) in t-PAPS and 41.8 (SD 13.9) in controls; most of the subjects were female. The mean expression of MPO was 1.05 (SD 1.02) in controls; 1.56 (SD 1.71) in t-PAPS and 3.62 (SD 5.56) in t-SAPS. The mean difference in MPO expression between t-SAPS and controls was 2.57 (95% CI 1.31; 3.84). The mean expression of ELANE was 2.23 (SD 3.11) in controls; 3.46 (SD 14.25) in t-PAPS and 13.36 (SD 36.72) in t-SAPS. The mean difference in ELANE expression between t-SAPS and controls was 11.13 (95% CI 2.48; 19.78). PADI4 expression was similar between APS and controls. Circulating levels of dsDNA and MPO-DNA did not differ between t-SAPS (22.27 and 0.18) t-PAPS (22.36 and 0.19) and controls (25.4 and 0.16, respectively). Levels of H3cit was decreased in t-SAPS when compared to controls (Tabe 2).
Conclusions: The expression of genes associated with neutrophil activity was up-regulated in patients with SAPS. Molecular and plasma markers of NETs, however, were not associated either with t-PAPS nor t-SAPS, which suggests that the observed neutrophil activity is not related to the production of NETs.
| Mean Levels (SD) | Mean difference no adjustments* (95% CI) | Mean Difference adjusted for age and sex * (95% CI) | |
| Controls (Free- dsDNA) | 5.42 (16.61) | Reference | Reference |
| t-PAPS (Free- dsDNA) | 22.36 (9.15) | -3.06 (-7.19; 1.07) | -3.05 (-7.16; 1.06) |
| t-SAPS (Free- dsDNA) | 22.27 (10.11) | -3.15 (-7.95; 1.65) | -2.52 (-7.13; 2.27) |
| Controls (MPO-DNA) | 0.16 (0.16) | Reference | Reference |
| t-PAPS (MPO-DNA) | 0.19 (0.15) | 0.04 (-0.01; 0.08) | 0.03 (-0.01; 0.07) |
| t-SAPS (MPO-DNA) | 0.18 (0.09) | 0.02 (-0.04; 0.07) | 0.02 (-0.03; 0.07) |
| Controls (H3-citrullinated) | 2.03 (1.56) | Reference | Reference |
| t-PAPS (H3-citrullinated) | 2.11 (1.77) | 0.08 (-0.43; 0.59) | 0.11 (-0.40; 0.62) |
| t-SAPS (H3-citrullinated) | 1.18 (1.57) | -0.85 (-1.44; – 0.25) | -0.85 (-1.44; – 0.25) |
[Table 1. Differences in the levels of NETs markers between controls, patients with thrombotic PAPS and SAPS]
| Mean levels (SD) | Mean difference no adjustments* (95% CI) | Mean Difference adjusted for age and sex * (95% CI) | |
| Controls (MPO) | 1.05 (1.02) | Reference | Reference |
| t-PAPS (MPO) | 1.56 (1.71) | 0.51 (-0.47; 1.49) | 0.41 (-0.58; 1.39) |
| t-SAPS (MPO) | 3.62 (5.56) | 2.57 (1.31; 3.84) | 2.55 (1.26; 3.84) |
| Controls (ELANE) | 2.23 (3.11) | Reference | Reference |
| t-PAPS (ELANE) | 3.46 (14.25) | 1.23 (-5.47; 7.92) | 1.00 (-5.82; 7.81) |
| Controls (ELANE) | 13.36 (36.72) | 11.13 (2.48; 19.78) | 11.41 (2.52; 20.31) |
| Controls (PAD4) | 0.96 (0.41) | Reference | Reference |
| t-PAPS (PAD4) | 1.10 (0.72) | 0.14 (-0.07; 0.36) | 0.12 (-0.09; 0.34) |
| t-SAPS (PAD4) | 0.95 (0.56) | -0.01 (-0.28; 0.27) | 0.05 (-0.23; 0.34) |
[Table 2. Differences in the expression of neutrophils-associated genes between controls, patients with thrombotic PAPS and SAPS]
To cite this abstract in AMA style:
Mazetto BM, Hounkpe BW, Santos APR, Jacintho B, Mesquita GLTV, Vaz CO, Annichino-Bizzacchi J, De Paula É, Orsi FLA. Neutrophil Activity in Patients with Antiphospholipid Syndrome-Related Thrombosis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/neutrophil-activity-in-patients-with-antiphospholipid-syndrome-related-thrombosis/. Accessed September 22, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/neutrophil-activity-in-patients-with-antiphospholipid-syndrome-related-thrombosis/