公开(公告)号：US20190350178A1

公开(公告)日：2019-11-21

申请号：US16479501

申请日：2018-01-22

Applicant: UNIVERSITÄTSKLINIKUM HAMBURG-EPPENDORF

Inventor： Tobias FUCHS ,  Miguel JIMENEZ-ALCAZAR ,  Chandini RANGASWAMY

IPC: A01K67/027 ,  C07K14/535 ,  A61K49/00 ,  G01N33/50

Abstract: The present invention relates to a non-human mammalian animal which has been modified to have in the blood, plasma and/or serum (a) an increased number of leukocytes and/or neutrophils, and (b) a reduced activity of the DNase 1 and/or DNase 1-like 3 enzymes. The non-human mammalian animal is particularly suitable for studying inflammation and/or a disease associated with inflammation. In a further aspect, the invention relates to the use of the non-human mammalian animal as a model for identifying therapeutic or diagnostic targets of inflammation and/or a disease associated with inflammation. In a still further aspect, the invention relates the use of the non-human mammalian animal as a model for drug candidate testing. In addition, a method for testing an anti-inflammatory drug candidate against extracellular DNA is provided. Finally, a method for testing an anti-inflammatory drug candidate for modifying the formation or degradation of neutrophil extracellular traps is provided. In still another aspect, the present invention relates to a non-human mammalian animal, which has been modified to have an increased number of neutrophils in blood.

公开(公告)号：US20190234936A1

公开(公告)日：2019-08-01

申请号：US16313618

申请日：2017-07-20

Applicant: UNIVERSITÄTSKLINIKUM HAMBURG-EPPENDORF

Inventor： Tobias FUCHS

IPC: G01N33/50 ,  G01N33/564 ,  G01N33/533

CPC classification number: G01N33/5005 ,  C07K16/42 ,  G01N33/533 ,  G01N33/564

Abstract: The invention relates to immunodiagnostic detection of anti-neutrophil antibodies. Object of the current invention is to improve the diagnosis of ANCA-associated diseases, in particular ANCA-associated vasculitides. For solving the problem, the invention provides in one aspect a method for the immunodiagnostic detection of anti-neutrophil antibodies, the method comprising: a1) Contacting an aliquot of a sample of body fluid with stimulated netotic but not netting polymorphonuclear neutrophils, PMNs, under conditions allowing binding of anti-neutrophil antibodies in the sample to the polymorphonuclear neutrophils, wherein the netotic but not netting polymorphonuclear neutrophils have been generated by treating stimulated, but not netting, polymorphonuclear neutrophils with a NET release inhibiting compound under conditions where the formation of NETs by the stimulated polymorphonuclear neutrophils is suppressed, and a2) Immunolabeling of anti-neutrophil antibodies bound to the stimulated netotic but not netting polymorphonuclear neutrophils. In further aspects the invention provides a method for preparing an object slide for the immunodiagnostic detection of anti-neutrophil antibodies, an object slide for the immunodiagnostic detection of anti-neutrophil antibodies, a kit for the immunodiagnostic detection of anti-neutrophil antibodies, and the use of stimulated neutrophils for the immunodiagnostic detection of anti-neutrophil antibodies.