Myeloperoxidase Anti-neutrophil Cytoplasmic Antibody Levels Research Articles

Avacopan's potential to decrease MPO-ANCA titres concurrent with ameliorated activity in ANCA-associated vasculitis.

Avacopan, an orally administered C5a receptor antagonist, is effective in microscopic polyangiitis via the inhibition of neutrophil priming induced by C5a. However, the exact effect of avacopan on the production of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is yet to be clearly established. This report presents a microscopic polyangiitis patient without major organ damage where high levels of MPO-ANCA persisted with high-dose steroid therapy and azathioprine, but the addition of avacopan led to a reduction in MPO-ANCA titres. The present case implies that avacopan-mediated inhibition of C5a may lead to a reduction in MPO-ANCA levels, thereby potentially ameliorating the pathophysiology of ANCA-associated vasculitis. Nevertheless, the impact of avacopan on MPO-ANCA production cannot be asserted solely based on this report; therefore, further examination is necessary through subgroup analysis using data from larger-scale studies.

Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis.

Background The subclinical pathophysiology of proliferative lupus nephritis (PLN) has not been fully elucidated. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is associated with PLN, but prediagnostic levels have not been reported. Methods We performed a retrospective case-control Department of Defense Serum Repository (DoDSR) study comparing MPO-ANCA levels in longitudinal prediagnostic serum samples for 23 biopsy confirmed proliferative lupus nephritis (PLN) patients to DoDSR identified age, sex, race, and age of serum matched healthy and SLE without LN disease controls. We also compared the temporal relationship of MPO-ANCA to anti-double stranded DNA antibodies (dsDNAab). Results A greater proportion of PLN patients had prediagnostic MPO-ANCA levels above ≥3 U/mL and ≥6 U/mL compared to SLE without LN (91% versus 43%, p < 0.001; 57% versus 5%, p < 0.001, resp.). In subgroup analysis, the MPO-ANCA threshold of ≥3 U/mL was significant at <1 year (88% versus 39%, p = 0.007) and 1–4 years (87% versus 38%, p = 0.009) prior to diagnosis. Statistically significant subclinical MPO-ANCA levels (≥3 U/mL) occurred prior to statistically significant dsDNAab ≥ 3 IU/ml (89% versus 11%, p = 0.003). Conclusions Subclinical MPO-ANCA levels could distinguish future PLN from SLE without LN. MPO-ANCA manifests prior to clinical disease and subclinical dsDNAab to suggest that it may contribute directly to PLN pathogenicity.

Clinical analysis of patients with myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis.

This prospective study analyzed the clinical characteristics of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis and explored the relationship between MPO-ANCA and clinical manifestations of the associated vasculitis in 132 p-ANCA and MPO-ANCA-positive patients (average age, 62.3 ± 14.8 years) who were initially diagnosed with ANCA-associated vasculitis. The p-ANCA and MPO-ANCA levels in peripheral blood were detected in all patients. Among these, 128 (97%) had microscopic polyangiitis (MPA), 3 (2.3%) had granulomatous polyangiitis, and 1 (0.7%) had eosinophilic granulomatous vasculitis. The average time of diagnosis was 10.2 ± 18 months; only 14 (10.6%) patients were diagnosed within 1 month. The main organs involved and the corresponding number of patients were: renal, 95 (72%); lung, 89 (67.4%); joints, 35 (26.5%); heart, 26 (19.7%); peripheral nerve, 23 (17.4%); skin rash, 14 (10.6%); and CNS, 13 (9.8%). Older patients were more likely to show lung involvement in the early disease stage, whereas the joints were involved mostly in the younger patients. The p-ANCA levels (mean titers, 1:60) were not correlated with disease activity and extent of organ involvement, and the MPO-ANCA levels were positively correlated with disease activity, but had no correlation with the extent of organ involvement. MPO-ANCA vasculitis is a common occurrence in China; it mainly involves the elderly and presents as clinical manifestations of MPA. However, the multiple organ damage is not specific leading to delay in diagnosis. MPO-ANCA may play a pathogenic role in the associated vasculitis, and the diverse clinical manifestations might be related with the different characteristics of MPO-ANCA.

Rheumatoid arthritis complicated with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis: a case report.

This article describes a patient with rheumatoid arthritis (RA) with crescentic glomerulonephritis (CrGN) associated with myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA), who responded well to methotrexate (MTX). A 48-year-old woman with a 4-year history of RA was admitted with fever and elevated C-reactive protein. On laboratory evaluation, her level of MPO-ANCA was 422 EU, and urinalysis revealed proteinuria and hematuria. Because she was also suffering from episcleritis, vasculitis was considered. A renal biopsy was performed, which revealed necrotizing CrGN. We diagnosed RA complicated with MPO-ANCA-associated vasculitis. We considered treatment with high-dose oral prednisolone for vasculitis, but the patient refused this treatment. We started MTX at a dose of 8 mg/week for RA from the time of admission, and the patient responded immediately. Biochemical parameters, including C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and MPO-ANCA, improved. Seven months later, MPO-ANCA had decreased to 46 EU. In clinical studies, few patients have been reported with RA complicated with ANCA-associated CrGN. This case differs from previous cases in the treatment given. No high-dose steroid with intensive immunosuppression or plasma exchange was required.

Successful treatment of refractory aortitis in antineutrophil cytoplasmic antibody-associated vasculitis using tocilizumab

A 47-year-old Japanese woman developed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) complicated by a rare combination of aortitis and hypertrophic pachymeningitis. Despite the therapy with prednisolone and cyclophosphamide, the aortitis was not ameliorated. However, after cyclophosphamide was replaced with intravenous tocilizumab, the aortitis was improved, and the prednisolone dose was successfully tapered to 4 mg/day without elevation in C-reactive protein and myeloperoxidase ANCA (MPO-ANCA) levels. Several studies have reported that tocilizumab is effective for aortitis associated with Takayasu's arteritis and giant cell arteritis. On the other hand, we succeeded to improve the aortitis in AAV with monthly administration of tocilizumab. Moreover, we successfully controlled disease activity and enabled the tapering of prednisolone to 4 mg/day without relapses of AAV symptoms and elevated MPO-ANCA levels. It indicates that tocilizumab may be therapeutically beneficial for not only aortitis but also AAV itself. In conclusion, tocilizumab was effective in treating glucocorticoid- and cyclophosphamide-resistant AAV-associated aortitis. This is the first report demonstrating the successful treatment of AAV-associated aortitis using tocilizumab.

A case presenting with the possible relationship between myeloperoxidase-antineutrophil cytoplasmic antibody-associated glomerulonephritis and membranous changes of the glomerular basement membrane.

A 72-year-old woman exhibited elevated serum myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) levels since 2006. Her serum creatinine (sCr) levels increased from 0.5 to 1.62mg/dl in a stepwise pattern with proteinuria and hematuria up to January 2011. Renal biopsy indicated global sclerosis (14%), fibrocellular crescents (28%), and Swiss cheese-like appearance of the glomerular basement membrane (GBM) on light microscopy. IgG4 staining was negative. Immunofluorescent examination indicated granular staining with IgG and C3 along the GBM. MPO-ANCA-associated glomerulonephritis with membranous nephropathy (MN) was diagnosed. As chronic changes were relatively evident in the renal biopsy specimen without acute augmentation of renal function, immunosuppressive therapy was not administered. Thereafter, rapidly progressive renal dysfunction occurred (sCr, 3.67mg/dl in May 2011) with proteinuria (~2g/day), hematuria, and elevated serum MPO-ANCA levels. Therefore, a second renal biopsy was performed in May 2011, indicating global sclerosis (42%) and cellular crescents (35%) on light microscopy. Electron microscopy indicated electron-dense deposits in the GBM and mesangial lesions. Steroid therapy was subsequently initiated, and the patient's renal function partially improved. MPO-ANCA levels decreased to within normal limits and hematuria disappeared. MPO-ANCA-associated glomerulonephritis with MN is a rare dual glomerulopathy. However, complication should be considered when urinary protein appears in large amounts. Secondary MN was suspected due to the lack of IgG4 staining and distribution of electron-dense deposits to the mesangial lesion. Renal dysfunction occurring in a stepwise pattern may be attributed to intermittent augmentation in MPO-ANCA-associated glomerulonephritis.

A Case of Sinobronchial Syndrome Complicated with Myeloperoxidase Antineutrophil Cytoplasmic Antibody Associated Vasculitis: Review of the Literature

We report a case of long-standing sinobronchial syndrome complicated by microscopic polyangiitis (MPA) during the clinical course. The patient showed a mild elevation of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) 17 months prior to the diagnosis of MPA. Subsequently, her MPO-ANCA level gradually became more elevated, and finally her MPO-ANCA level peaked when purpura appeared. Histologic examination of the skin biopsy was consistent with leukocytoclastic vasculitis. Based on the pathological and clinical findings, a diagnosis of MPA was made. Corticosteroid therapy finally led to a remission of MPA with normalized MPO-ANCA titers.

Resolution of anti-neutrophil cytoplasmic antibody-associated vasculitis after resection of gastric cancer

We report a case of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis in a 62-year-old patient with gastric cancer. The myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) level was threefold above normal preoperatively. Vasculitis was seen on renal biopsy. Gastric resection revealed well-differentiated adenocarcinoma and vasculitis. The MPO-ANCA level returned to normal post-operatively. Although ANCA-associated vasculitis occasionally accompanies malignant tumors, this is the first documented case of concurrent gastric cancer-associated and ANCA-associated vasculitis, with post-operative resolution of the vasculitis.

A Novel Mouse Model for MPO‐ANCA‐Associated Glomerulonephritis

We established a novel model mouse for myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis with crescentic formation, which was induced by administering bovine serum albumin (BSA). Neutrophil infiltration into the renal glomeruli began at 8 weeks and crescent formation was observed from 10 weeks after the first BSA injection. Platelet and neutrophil counts significantly increased, and proteinuria was observed from 5 weeks. MPO-ANCA increased slightly at 4 and markedly at 9 weeks, and the TNF-alpha level increased at 11 weeks. Glomerular neutrophil infiltration was correlated with MPO-ANCA levels. In addition, proteinuria also significantly correlated with MPO-ANCA levels. Finally, renal crescent formation was associated with an increase of MPO-ANCA levels and neutrophil infiltration into glomeruli. The glomerular immune deposition of IgG and C3 was observed. These findings indicate that BSA induces neutrophil activation of peripheral blood followed by the elevation of MPO-ANCA, resulting in the development of crescentic glomerulonephritis in mice.

Pulmonary fibrosis in myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitides.

The association of pulmonary fibrosis (PF) with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitides has not been well documented. The aim of this study was to assess the clinicopathological characteristics of PF in patients who tested positive for MPO-ANCA. In this study, 31 patients (17 males and 14 females; mean age, 69 years) diagnosed as having PF with positive MPO-ANCA levels ranging from 10 to 840 EU with a mean of 112.5 EU, were evaluated clinicopathologically. Among 31 patients with PF, 22 had underlying systemic diseases such as collagen vascular diseases, while nine had unknown aetiology. Evidence of glomerulonephritis was demonstrated in 14 patients. The clinical features were a history of dry cough and/or fine crackles in all 31 patients. Chest CT scans showed honeycombing in the lung bases in 26 patients. The histopathological features of the diseased lung tissues in all 11 autopsied cases were compatible with the usual interstitial pneumonia (UIP) pattern. Vasculitis was confirmed in bronchial arteries and/or pulmonary arterioles in five patients. The mortality was as high as 13 of the 31 patients. The causes of death were: deterioration of PF in five (two of whom were associated with pulmonary haemorrhage), lung cancer in two, pneumonia in four, and digestive tract bleeding in two. The survival rates in PF with MPO-ANCA-negative collagen vascular diseases, cryptogenic fibrosing alveolitis (CFA), and PF with positive MPO-ANCA, were compared. The 5-year survival rate in PF with positive MPO-ANCA was worse than in PF with MPO-ANCA-negative collagen vascular diseases and was the same for CFA. Although there was no correlation between MPO-ANCA titres and the activity of PF, this study demonstrated that the presence of positive MPO-ANCA was an unfavorable prognostic factor in patients with PF.

Clinical features of bilateral progressive hearing loss associated with myeloperoxidase-antineutrophil cytoplasmic antibody.

In this study, we analyzed the clinical features, diagnostic criteria, treatment, and outcome of atypical bilateral progressive hearing loss associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). The evaluation was made by audiogram and laboratory data in 6 cases treated at Hokkaido University Hospital. We measured MPO-ANCA by enzyme-linked immunosorbent assay; the result was positive in all cases. The hearing loss developed bilaterally and progressed to total deafness within several weeks. The onset of hearing loss was not simultaneous in the 2 ears. Methylprednisolone pulse therapy was effective in 9 ears. Three ears showed no improvement; 2 of the 3 ears had already exhibited total deafness at the first visit. After the treatment, the titer of MPO-ANCA decreased in all patients. The level of MPO-ANCA should be tested in patients with bilateral progressive hearing loss of unknown origin and can be used as a marker of the disease's activity.

Simultaneous occurrence of diabetic glomerulosclerosis, IgA nephropathy, crescentic glomerulonephritis, and myeloperoxidase-antineutrophil cytoplasmic antibody seropositivity in a chinese patient

We report the case of a 72-year-old woman with a long-standing history of diabetes mellitus who presented with heavy proteinuria and rapid deterioration in renal function. She had a high titer of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). The renal biopsy specimen revealed features of diabetic glomerulosclerosis, crescentic glomerulonephritis, and IgA nephropathy. Treatment with steroid and cyclophosphamide resulted in significant improvement in renal function and normalization of MPO-ANCA level. This case highlights the importance of having a high index of suspicion for coexisting glomerulonephritis in diabetic patients presenting with proteinuria. The clinical course of patients with diabetic glomerulosclerosis, IgA nephropathy, crescentic glomerulonephritis, and MPO-ANCA seropositivity seems to resemble that of ANCA-associated, rapidly progressive glomerulonephritis and is potentially amenable to aggressive immunosuppressive therapy. © 2002 by the National Kidney Foundation, Inc.