Elevated plasma neutrophil elastase concentration is associated with disease activity in patients with thrombotic thrombocytopenic purpura

Abstract

Keywords:Polymorphonuclear leukocyte neutrophil granulocyte elastase thrombotic thrombocytopenic purpura disease activity complement activation Introduction: Genetic and autoimmune risk factors contribute to the development of thrombotic thrombocytopenic purpura (TTP) but triggers are needed to bring about acute disease. The aim of the study was to investigate the association of neutrophil activation with acute TTP, to assess whether neutrophil activation changes during plasma exchange therapy and to show if complement-and neutrophil activation are parallel, characteristic processes in acute TTP. Materials and Methods: Altogether 49 EDTA-plasma samples of 21 TTP patients with acute disease and 17 in remission were investigated along with 20 healthy controls. A stable complex of PMNE-proteinase-inhibitor was measured by ELISA (Calbiochem, Merck-Millipore, Darmstadt, Germany). Results: Acute disease was associated with significantly increased PMNE levels, the group medians were similarly low in TTP patients in remission and in healthy controls. Increased PMNE levels were characteristic for hematologically active and ADAMTS13 deficient form of TTP. PMNE concentration inversely correlated to disease activity markers platelet count (r = − 0.349, p = 0.032) and hemoglobin levels (p = − 0.382 p = 0.018). Achievement of remission was associated with significant reduction of plasma PMNE levels (p = 0.031, Wilcoxon test). There was positive correlation between PMNE levels and complement activation markers C3a and Bb. Conclusions: We report increased PMNE levels in acute TTP and showed its association to activity markers of acute TTP and complement activation. Effective treatment of an acute TTP episode resulted in marked decrease in PMNE levels. Our data support and extend previous observations that neutrophil extracellular traps may be released in acute TTP and potentially contribute to the pathophysiology of this disease.

Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura

“…20,21 To determine if HNP1-3 are released from activated neutrophils, we measured their plasma concentrations in patients with acute TTP by an immunoassay. As shown in Table 2 and Figure 1C, the median plasma level of HNP1-3 in acute TTP patients was 33.1 (12.8-239.4) ng/ml, significantly higher than the median level of 2.4 (1.8-14.5) in the blood donor controls (P<0.0001).…”

Decreased Neutrophil Extracellular Trap Degradation in Shiga Toxin-Associated Haemolytic Uraemic Syndrome

“…Elevated levels of circulating DNA have been reported in TMA patients [8] , and we previously reported increased levels of neutrophil elastase in acute TTP, which is associated with disease activity markers of acute TTP [9] . These observations in combination with recent reports of a decreased degradation of neutrophil extracellular traps (NETs) in TMA [10] and increased formation of NETs [11] have suggested a role for NETs in thrombotic microangiopathic disorders.…”

Neutrophil Protease Cleavage of Von Willebrand Factor in Glomeruli – An Anti-thrombotic Mechanism in the Kidney

“…Elevated neutrophil elastase occurring during infectious episodes (Mikes et al, 2014) could explain why certain TTP patients are partially protected and remain asymptomatic for long periods in spite of ADAMTS13 deficiency. TTP recurrences are often triggered by infections during which neutrophils infiltrate tissue.…”