Myeloperoxidase anti-neutrophil cytoplasmic antibody affinity is associated with the formation of neutrophil extracellular traps in the kidney and vasculitis activity in myeloperoxidase anti-neutrophil cytoplasmic antibody-associated microscopic polyangii

Anti-neutrophil cytoplasmic antibody (ANCA) is associated with small-vessel vasculitis particularly in the kidneys and can induce the formation of neutrophil extracellular traps (NETs) from primed neutrophils. Recently we have reported that the induction of NETs correlates with ANCA affinity for myeloperoxidase (MPO) and disease activity in patients with MPO-ANCA-associated microscopic polyangiitis. To investigate whether MPO-ANCA affinity is associated with the formation of NETs in vivo, we examined the occurrence of NETs in the renal tissues of patients with MPO-ANCA-associated microscopic polyangiitis and ANCA affinity by double immunofluorescence staining for NET components of citrullinated histone, MPO and PAD4 and by ELISA competition with MPO, respectively. We divided 30 MPO-ANCA-associated microscopic polyangiitis patients into 2 groups based on their ANCA affinity levels (IC50 for the high: 0.11 ± 0.04 µg/mL (Group1) and IC50 for the low: 0.66 ± 0.24 µg/mL (Group2)). Group1 showed a higher Birmingham vasculitis activity score (15.6 ± 5.7) and 73% of the patients presented clinically with rapidly progressive glomerulonephritis and histologically with focal/crescentic glomerulonephritis (GN). Group 2 showed a lower Birmingham vasculitis activity score (9.2 ± 4.9) and 73% of the patients presented clinically with chronic renal failure and histologically with mixed/sclerotic GN. Group 1 showed a much higher occurrence of NETs than Group 2. Our findings indicate that ANCA affinity was associated with the in vivo formation of NETs, which might be involved in the pathophysiology of patients with MPO-ANCA-associated microscopic polyangiitis.

Yoshida M ，Yamada M ，Sudo Y ，Kojima T ，Tomiyasu T ，Yoshikawa N ，Oda T ，Yamada M ... -  《-》

Neutrophil extracellular traps in neuropathy with anti-neutrophil cytoplasmic autoantibody-associated microscopic polyangiitis.

Takeuchi H ，Kawasaki T ，Shigematsu K ，Kawamura K ，Oka N ... -  《-》

Two types of myeloperoxidase-antineutrophil cytoplasmic autoantibodies with a high affinity and a low affinity in small vessel vasculitis.

Yoshida M ，Sasaki M ，Nakabayashi I ，Akashi M ，Tomiyasu T ，Yoshikawa N ，Kojima T ，Ohno N ，Yamada M ... -  《CLINICAL AND EXPERIMENTAL RHEUMATOLOGY》

The presence of anti-neutrophil extracellular trap antibody in patients with microscopic polyangiitis.

Although ANCA is the major autoantibody in patients with ANCA-associated vasculitis, previous studies have suggested the presence of anti-neutrophil extracellular trap (NET) antibody in patients with microscopic polyangiitis (MPA), one type of ANCA-associated vasculitis. In this study, we aimed to determine the prevalence and pathogenic role of anti-NET antibody (ANETA) in MPA. We examined the presence or absence of ANETA in sera obtained from 19 MPA patients by indirect immunofluorescence. We compared the clinical parameters, including age, sex, MPO-ANCA, creatinine, CRP, MPO-DNA complexes and vasculitis activity, in ANETA-positive and ANETA-negative MPA patients. We investigated the serum NET induction and degradation abilities of ANETA-positive and ANETA-negative MPA patients with reference to healthy controls (n = 8). Furthermore, we assessed the relationship between ANETA and the effect of IgG depletion on the serum NET degradation ability. ANETA was present in 10 of the 19 MPA patients. There was no significant difference in the clinical parameters in ANCA-positive and ANCA-negative MPA patients. Although the NET induction ability was higher and the NET degradation ability was lower in MPA sera than those in healthy controls, these abilities were not different between ANETA-positive and ANETA-negative MPA sera. Interestingly, the NET degradation ability in some sera with ANETA was markedly increased by IgG depletion. Some MPA patients produce ANETA and some ANETA possess an inhibitory function against the serum NET degradation ability. Although further studies are needed, ANETA is worthy of attention in order to understand the pathophysiology of MPA.

Hattanda F ，Nakazawa D ，Watanabe-Kusunoki K ，Kusunoki Y ，Shida H ，Masuda S ，Nishio S ，Tomaru U ，Atsumi T ，Ishizu A ... -  《-》

Anti-neutrophil extracellular trap antibody in a patient with relapse of anti-neutrophil cytoplasmic antibody-associated vasculitis: a case report.

Shida H ，Hashimoto N ，Kusunoki Y ，Hattanda F ，Ogawa Y ，Hayashi T ，Nakazawa D ，Masuda S ，Tomaru U ，Ishizu A ... -  《BMC Nephrology》