Biomarkers of membranous glomerulonephritis
Inventors
STAHL, Rolf • Hoxha, Elion • Reinhard, Linda
Assignees
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Publication Number
US-12306184-B2
Publication Date
2025-05-20
Expiration Date
Abstract
Netrin G1 is disclosed as a biomarker of membranous glomerulonephritis (MGN). Netrin G1 antigen-comprising polypeptides and Netrin G1 antibodies can be used in in vitro methods and kits for diagnosis, prognosis and monitoring of MGN of patients with circulating Netrin G1 autoantibodies.
Core Innovation
The disclosed invention identifies Netrin G1 (NTNG1) as a novel autoantigen and/or biomarker for membranous glomerulonephritis (MGN). It provides in vitro diagnostic, prognostic, and therapeutic effectiveness monitoring approaches based on detection of anti-NTNG1 autoantibodies and/or detection of NTNG1 expression in biological samples obtained from a subject. The approach supports non-invasive biomarker testing for diagnosis of NTNG1-positive MGN and longitudinal follow-up.
The disclosed rationale includes detection of antigenantibody complexes, including embodiments where anti-NTNG1 autoantibodies are detected optionally as antigenantibody complexes formed with NTNG1. The partial content further describes assay suitability for non-reducing gentle/Tank-Blot Western blot conditions, and it contrasts Tank-Blot transfer with semi-dry transfer. Validation described in the partial content includes non-reducing Western blot and immunohistochemistry, including the assessment of NTNG1 recognition and identification of NTNG1.
The disclosed invention also includes methods for determining therapeutic effectiveness by assessing longitudinal changes in anti-NTNG1 autoantibody levels, using first and second biological samples at first and second time-points. For prognosis, the invention compares the expression level of human NTNG1 polypeptide or anti-human NTNG1 antibody-binding fragments in a biological sample to a reference expression level, where increased expression is indicative of MGN. The partial content further describes kit/device concepts using immobilized NTNG1 polypeptides or anti-NTNG1 antibody-binding fragments and detection reagents for performing such in vitro measurements.
Claims Coverage
The partial content indicates three independent in vitro methods directed to: (i) detecting anti-human NTNG1 autoantibodies in a subject-derived biological sample, (ii) determining treatment effectiveness for MGN using anti-NTNG1 autoantibody level changes at two time-points during immunosuppressive treatment, and (iii) prognosing MGN by comparing NTNG1 expression level to a reference level and subsequently treating MGN with immunosuppressive pharmaceutical substances. Across these independent claims, the core inventive features are centered on NTNG1/anti-NTNG1 detection, antigenantibody complex detection, longitudinal comparison, and reference-level comparison for prognosis.
Detecting autoantibodies recognizing human NTNG1 polypeptide in vitro
An in vitro method detecting one or more autoantibodies recognizing a human Netrin G1 (NTNG1) polypeptide or one or more anti-human NTNG1 antibody-binding fragments thereof in a biological sample obtained from a subject.
Treatment effectiveness based on anti-human NTNG1 autoantibody levels at first and second time-points
An in vitro method of determining the effectiveness of treatment for MGN in a subject by (i) treating the subject diagnosed with MGN with one or more immunosuppressive pharmaceutical substances, (ii) determining a level of anti-human NTNG1 autoantibodies in a first biological sample at a first time-point, and (iii) determining a level of anti-human NTNG1 autoantibodies in a second biological sample at a second time-point, wherein a decrease indicates effective treatment and/or an increase indicates not effective treatment, and continuing the effective treatment by administering the one or more immunosuppressive pharmaceutical substances.
Prognosis of MGN by comparing NTNG1 expression level to a reference level
An in vitro method for prognosis of MGN in a subject by determining the expression level of human NTNG1 polypeptide or one or more anti-human NTNG1 antibody-binding fragments in a biological sample, comparing the expression level to a reference expression level where an increased expression level compared to the reference is indicative of MGN, and treating the MGN by administering one or more immunosuppressive pharmaceutical substances.
Overall, the independent claims cover in vitro detection of anti-NTNG1 autoantibodies using human NTNG1 polypeptide or anti-human NTNG1 antibody-binding fragments, determination of treatment effectiveness by longitudinal comparison of anti-NTNG1 autoantibody levels at two time-points during immunosuppressive treatment, and prognosis by comparing NTNG1-related expression levels in a biological sample to a reference expression level followed by immunosuppressive treatment.
Stated Advantages
Supports non-invasive biomarker testing for diagnosis of NTNG1-positive MGN.
Enables determination of therapeutic effectiveness by indicating effectiveness via decreased anti-human NTNG1 autoantibody levels at a later time-point compared to an earlier time-point.
Enables prognosis of MGN by indicating that increased NTNG1 expression level compared to a reference expression level is indicative of MGN.
Documented Applications
In vitro diagnostic detection of anti-NTNG1 autoantibodies for diagnosis of NTNG1-positive membranous glomerulonephritis (MGN) using biological samples from a subject.
In vitro prognosis of membranous glomerulonephritis (MGN) by comparing expression level of human NTNG1 polypeptide or anti-human NTNG1 antibody-binding fragments to a reference expression level.
In vitro monitoring of therapeutic effectiveness in a subject with MGN receiving one or more immunosuppressive pharmaceutical substances by assessing changes in anti-human NTNG1 autoantibody levels across time-points.
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