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Anti–Neutrophil Extracellular Trap Antibodies and Impaired Neutrophil Extracellular Trap Degradation in Antiphospholipid Syndrome
Author(s) -
Zuo Yu,
Yalavarthi Srilakshmi,
Gockman Kelsey,
Madison Jacqueline A.,
Gudjonsson Johann E.,
Kahlenberg J. Michelle,
Joseph McCune W.,
Bockenstedt Paula L.,
Karp David R.,
Knight Jason S.
Publication year - 2020
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41460
Subject(s) - neutrophil extracellular traps , antiphospholipid syndrome , medicine , autoantibody , antibody , immunology , thrombosis , isotype , venous thrombosis , gastroenterology , inflammation , monoclonal antibody
Objective The release of neutrophil extracellular traps (NETs) by hyperactive neutrophils has recently been recognized to play an important role in antiphospholipid syndrome (APS). This study was undertaken to evaluate autoantibodies targeting NETs in patients with primary APS, and to determine their potential functions and clinical associations. Methods We measured global anti‐NET activity in 76 patients with primary APS, 23 patients with systemic lupus erythematosus without antiphospholipid antibodies (aPL), 11 patients with a history of unprovoked venous thrombosis without aPL, and 44 healthy controls. The ability of APS sera to degrade NETs was also assessed. Results We found markedly elevated levels of anti‐NET IgG and IgM in patients with primary APS compared with healthy controls (for IgG, mean ± SD optical density 0.55 ± 0.34 versus 0.33 ± 0.17; for IgM, mean ± SD optical density 0.76 ± 0.51 versus 0.26 ± 0.23). This anti‐NET activity did not correlate with levels of traditional aPL and was relatively stable over time. Mechanistically, anti‐NET antibodies (especially of the IgG isotype) impaired the ability of patient sera to degrade NETs (r = 0.4, P = 0.003). Levels of anti‐NET IgM inversely correlated with complement C4 (r = 0.4, P = 0.019). Clinically, anti‐NET antibodies associated with certain APS clinical manifestations, and in particular recurrent venous thrombosis (odds ratio 4.3; P = 0.002). Interestingly, anti‐NET antibody levels also appeared to be associated with unprovoked venous thrombosis in the general population (for IgM, mean ± SD optical density 0.67 ± 0.34 versus 0.26 ± 0.23). Conclusion Our data indicate high levels of anti‐NET antibodies in patients with primary APS, which may impair NET clearance and activate the complement cascade. These findings may ultimately enable more effective risk stratification.