Influence of myeloperoxidase by anti-myeloperoxidase antibodies and its association with the disease activity in microscopic polyangiitis.
OBJECTIVE
ANCAs with specificity for MPO are serological markers of ANCA-associated vasculitides, especially microscopic polyangiitis (MPA). This study investigated potential associations between the influence of MPO-ANCA on the oxidation activity of MPO and the clinical manifestations as well as immunological characteristics of MPO-ANCA.


METHODS
MPO-ANCA was purified with MPO-affinity chromatography from plasma of 13 consecutive patients with MPO-ANCA-positive MPA. The titre, avidity, immunoglobulin G (IgG) subclasses and the ability to reverse the binding between ceruloplasmin and MPO of MPO-ANCA were tested using ELISA. The oxidation activity of MPO in the presence of MPO-ANCA was measured. The associations between the oxidation activity of MPO after binding MPO-ANCA and the clinical and immunological characteristics of MPO-ANCA were analysed.


RESULTS
The MPO activity without binding to its autoantibodies was 1.521 (0.12) (expressed by A-values at 10 min, using o-phenylenediamine as substrate). After binding affinity-purified MPO-ANCA, the MPO activity ranged from 1.083 to 1.642. Correlation analysis showed that the oxidation activity of MPO after binding MPO-ANCA positively correlated with the level of ceruloplasmin binding on MPO in presence of MPO-ANCA (r = 0.617, P = 0.025) and negatively correlated with initial sera creatinine levels (r = -0.564, P = 0.045), BVAS (r = -0.735, P = 0.004), avidity of MPO-ANCA (r = -0.575, P = 0.040), levels of IgG2 (r = -0.610, P = 0.027) and IgG3 subclasses (r = -0.695, P = 0.008) of MPO-ANCA.


CONCLUSIONS
MPO-ANCA from different patients can influence MPO activity with different levels. The low oxidation activity of MPO after binding MPO-ANCA might be associated with more severe disease.
Xu
Peng-Cheng
PC
Department of Medicine, Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Beijing, China.
Chen
Min
M
Cui
Zhao
Z
Zhao
Ming-Hui
MH
D000293:Adolescent; D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D055953:Microscopic Polyangiitis / Q000276:immunology*; D008875:Middle Aged; D009195:Peroxidase / Q000276:immunology* / Q000502:physiology*; D055815:Young Adult
D019268:Antibodies, Antineutrophil Cytoplasmic; D009195:Peroxidase