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Clinical and functional consequences of anti-properdin autoantibodies in patients with lupus nephritis
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  • Maria Radanova,
  • Galya Mihaylova,
  • Desislava Ivanova,
  • Marie Daugan,
  • Valetin Lazarov,
  • Lubka Roumenina,
  • Vasil Vasilev
Maria Radanova
Medical University Varna Prof Dr Paraskev Stoyanov
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Galya Mihaylova
Medical University Varna Prof Dr Paraskev Stoyanov
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Desislava Ivanova
Medical University Varna Prof Dr Paraskev Stoyanov
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Marie Daugan
INSERM
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Valetin Lazarov
Medical University of Sofia
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Lubka Roumenina
INSERM
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Vasil Vasilev
Medical University of Sofia
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Abstract

Properdin is the only one positive regulator of the complement system. In this study, we characterize the prevalence, functional consequences and disease associations of autoantibodies against properdin in a cohort of patients with autoimmune disease systemic lupus erythematosus (SLE), suffering from lupus nephritis (LN). We detected autoantibodies against properdin in plasma of 22.5% of the LN patients (16/71) by ELISA. The binding of these autoantibodies to properdin was dose-dependent and was validated by surface plasmon resonance. Higher levels of anti-properdin were related to high levels of anti-dsDNA and ANA and to low concentrations of C3 and C4 in patients and also with histological signs of LN activity and chronicity. The high negative predictive value (NPV) of anti-properdin and anti-dsDNA combination suggested that patients who are both negative for anti-properdin and anti-dsDNA will not have severe nephritis. IgG from anti- properdin positive patients’ plasma increased the C3b deposition on late apoptotic cells by flow cytometry. Nevertheless, these IgGs did not modify substantially the binding of properdin to C3b, the C3 convertase C3bBb and the pro-convertase C3bB, evaluated by surface plasmon resonance. In conclusion, anti- properdin autoantibodies exist in LN patients. They have weak but relevant functional consequences, which could have pathological significance.

Peer review status:ACCEPTED

23 Mar 2020Submitted to Clinical & Experimental Immunology
25 Mar 2020Submission Checks Completed
25 Mar 2020Assigned to Editor
25 Mar 2020Reviewer(s) Assigned
02 Apr 2020Review(s) Completed, Editorial Evaluation Pending
02 Apr 2020Editorial Decision: Revise Minor
08 Apr 20201st Revision Received
09 Apr 2020Review(s) Completed, Editorial Evaluation Pending
09 Apr 2020Editorial Decision: Accept