Clinical and functional consequences of anti‐properdin autoantibodies in patients with lupus nephritis

Summary Properdin is the only 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...

Full description

Saved in:
Bibliographic Details
Published in:Clinical and experimental immunology 2020-08, Vol.201 (2), p.135-144
Main Authors: Radanova, M., Mihaylova, G., Ivanova, D., Daugan, M., Lazarov, V., Roumenina, L., Vasilev, V.
Format: Article
Language:English
Subjects:
Adult
Antibodies, Antinuclear - blood
Antigen-Antibody Complex - metabolism
Apoptosis
Autoantibodies
Autoantibodies - blood
Autoimmune diseases
Cohort Studies
complement
Complement C3 - metabolism
Complement C4 - metabolism
Complement component C3
Complement component C3b
Complement component C4
Complement system
Disease Progression
Enzyme-linked immunosorbent assay
Flow cytometry
Humans
Immunoglobulin G
Immunoglobulin G - blood
Kidney - metabolism
Kidney - pathology
Lupus
Lupus Erythematosus, Systemic - immunology
Lupus nephritis
Lupus Nephritis - immunology
Nephritis
Original
Predictive Value of Tests
Properdin
Properdin - immunology
Surface plasmon resonance
Systemic lupus erythematosus
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Properdin is the only 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 of 71) by enzyme‐linked immunosorbent assay (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 anti‐nuclear antibodies and 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 negative for both anti‐properdin and anti‐dsDNA will not have severe nephritis. Immunoglobulin G 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. Autoantibodies targeting the only positive regulator of the innate immune complement cascade were discovered in over 20% of the patients with lupus nephritis (16/71). 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. They also correlated with histological signs of lupus nephritis activity and chronicity.
ISSN:0009-9104
1365-2249
DOI:10.1111/cei.13443