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.