Peng-Cheng Xu1, Zhao Cui, Min Chen, Thomas Hellmark, Ming-Hui Zhao. 1. Department of Medicine, Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.
Abstract
OBJECTIVE: Natural autoantibodies (NAAs) against MPO exist in normal human plasma. In the current study, the immune characteristics of MPO-NAA and MPO-ANCA were examined and compared with the aim to investigate the pathogenesis of MPO-ANCA. METHODS: MPO-NAAs were affinity purified from normal plasma of five healthy blood donors and one batch of IVIG. MPO-ANCAs were purified from plasma of 10 patients with MPA. Antigen specificity of the antibodies was tested by western blot analysis. The titre, the avidity, the Immunoglobulin G (IgG) subclasses and the effect of the antibodies towards the binding between ceruloplasmin and MPO were tested using ELISAs. The MPO-NAA-induced production of reactive oxygen species was assessed using oxidation of dihydrorhodamine (DHR) to rhodamine. RESULTS: MPO-NAA recognized epitope(s) in the heavy chains of MPO with conformation-dependent structure, the same as MPO-ANCA. The median titre of MPO-NAA was lower than that of MPO-ANCA (1 : 40 vs 1 : 4800, P < 0.001). The median avidity of MPO-NAA was lower than that of MPO-ANCA (2.2 × 10(7) vs 8.7 × 10(7)/M, P = 0.014). The IgG subclasses of MPO-NAA were mainly restricted to IgG1 (100%) and lack of IgG3. The inhibition effect on the binding between ceruloplasmin and MPO was lower for MPO-NAA than MPO-ANCA (P = 0.046). The MPO-NAA-induced respiratory burst of neutrophils was significantly weaker than that of MPO-ANCA (P = 0.036). CONCLUSION: The lower titre, lower avidity and lack of IgG3 subclass compared with MPO-ANCA may contribute to the non-pathogenic co-existence of MPO-NAA with MPO in serum.
OBJECTIVE: Natural autoantibodies (NAAs) against MPO exist in normal human plasma. In the current study, the immune characteristics of MPO-NAA and MPO-ANCA were examined and compared with the aim to investigate the pathogenesis of MPO-ANCA. METHODS:MPO-NAAs were affinity purified from normal plasma of five healthy blood donors and one batch of IVIG. MPO-ANCAs were purified from plasma of 10 patients with MPA. Antigen specificity of the antibodies was tested by western blot analysis. The titre, the avidity, the Immunoglobulin G (IgG) subclasses and the effect of the antibodies towards the binding between ceruloplasmin and MPO were tested using ELISAs. The MPO-NAA-induced production of reactive oxygen species was assessed using oxidation of dihydrorhodamine (DHR) to rhodamine. RESULTS:MPO-NAA recognized epitope(s) in the heavy chains of MPO with conformation-dependent structure, the same as MPO-ANCA. The median titre of MPO-NAA was lower than that of MPO-ANCA (1 : 40 vs 1 : 4800, P < 0.001). The median avidity of MPO-NAA was lower than that of MPO-ANCA (2.2 × 10(7) vs 8.7 × 10(7)/M, P = 0.014). The IgG subclasses of MPO-NAA were mainly restricted to IgG1 (100%) and lack of IgG3. The inhibition effect on the binding between ceruloplasmin and MPO was lower for MPO-NAA than MPO-ANCA (P = 0.046). The MPO-NAA-induced respiratory burst of neutrophils was significantly weaker than that of MPO-ANCA (P = 0.036). CONCLUSION: The lower titre, lower avidity and lack of IgG3 subclass compared with MPO-ANCA may contribute to the non-pathogenic co-existence of MPO-NAA with MPO in serum.
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