Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies
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Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies. / Fuchs, Tobias A; Kremer Hovinga, Johanna A; Schatzberg, Daphne; Wagner, Denisa D; Lämmle, Bernhard.
in: BLOOD, Jahrgang 120, Nr. 6, 09.08.2012, S. 1157-64.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies
AU - Fuchs, Tobias A
AU - Kremer Hovinga, Johanna A
AU - Schatzberg, Daphne
AU - Wagner, Denisa D
AU - Lämmle, Bernhard
PY - 2012/8/9
Y1 - 2012/8/9
N2 - Thrombotic microangiopathies (TMAs) are a group of life-threatening disorders characterized by thrombocytopenia, fragmentation of erythrocytes, and ischemic organ damage. Genetic disorders, autoimmune disease, and cancer are risk factors for TMAs, but an additional, unknown trigger is needed to bring about acute disease. Recent studies suggest that DNA and histones are released during inflammation or infection and stimulate coagulation, thrombosis, thrombocytopenia, and organ damage in mice. We show that extracellular DNA and histones as well as markers of neutrophils are present in acute TMAs. Analysis of plasma from TMA patients of different clinical categories revealed elevated levels of DNA-histone complexes and myeloperoxidase (MPO) from neutrophil granules as well as S100A8/A9, a heterocomplex abundant in neutrophil cytosol. During therapy of thrombotic thrombocytopenic purpura, a subtype of TMAs often associated with severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) deficiency, plasma DNA and MPO were inversely correlated with platelet counts, and their levels indicated amelioration or exacerbation of the disease. ADAMTS13 deficiency together with increased levels of plasma DNA and MPO were characteristic for acute thrombotic thrombocytopenic purpura. A minor infection often precedes acute TMA and extracellular DNA and histones released during the inflammatory response could provide the second hit, which precipitates acute TMA in patients with pre-existing risk factors.
AB - Thrombotic microangiopathies (TMAs) are a group of life-threatening disorders characterized by thrombocytopenia, fragmentation of erythrocytes, and ischemic organ damage. Genetic disorders, autoimmune disease, and cancer are risk factors for TMAs, but an additional, unknown trigger is needed to bring about acute disease. Recent studies suggest that DNA and histones are released during inflammation or infection and stimulate coagulation, thrombosis, thrombocytopenia, and organ damage in mice. We show that extracellular DNA and histones as well as markers of neutrophils are present in acute TMAs. Analysis of plasma from TMA patients of different clinical categories revealed elevated levels of DNA-histone complexes and myeloperoxidase (MPO) from neutrophil granules as well as S100A8/A9, a heterocomplex abundant in neutrophil cytosol. During therapy of thrombotic thrombocytopenic purpura, a subtype of TMAs often associated with severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) deficiency, plasma DNA and MPO were inversely correlated with platelet counts, and their levels indicated amelioration or exacerbation of the disease. ADAMTS13 deficiency together with increased levels of plasma DNA and MPO were characteristic for acute thrombotic thrombocytopenic purpura. A minor infection often precedes acute TMA and extracellular DNA and histones released during the inflammatory response could provide the second hit, which precipitates acute TMA in patients with pre-existing risk factors.
KW - Acute Disease
KW - Adolescent
KW - Adult
KW - Aged
KW - Case-Control Studies
KW - Cohort Studies
KW - DNA
KW - Disease Progression
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Nucleosomes
KW - Peroxidase
KW - Prognosis
KW - Remission Induction
KW - Thrombotic Microangiopathies
U2 - 10.1182/blood-2012-02-412197
DO - 10.1182/blood-2012-02-412197
M3 - SCORING: Journal article
C2 - 22611154
VL - 120
SP - 1157
EP - 1164
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 6
ER -