Titer Of Myeloperoxidase-antineutrophil Cytoplasmic Antibody Research Articles

Improvement of rapidly progressive lupus nephritis associated MPO-ANCA with tacrolimus

A 43-year-old Japanese woman with systemic lupus erythematosus (SLE) developed rapidly progressive renal failure and nephritic syndrome with a high titer of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). Methylprednisolone pulse therapy did not suppress the progression of renal failure. Intravenous cyclophosphamide pulse therapy and administration of azathioprine was abandoned due to adverse effects. Tacrolimus was employed as an alternative immunosuppressive therapy and was well tolerated, effectively preventing renal failure. Oral prednisolone dosage was successfully tapered without recurrence, along with decreasing titer of MPO-ANCA. Renal biopsy showed diffuse proliferative lupus nephritis (International Society of Nephrology/Renal Pathology Society class IV-G A/C) with crescent formation. These findings indicate that in addition to lupus nephritis, which usually results from deposition of circulating or locally formed immune complexes, MPO-ANCA may be involved in the pathogenesis of crescentic glomerulonephritis. Furthermore, we propose that tacrolimus is an effective immunosuppressant for MPO-ANCA-related renal crisis in diffuse proliferative lupus nephritis.

Clinical Characteristics of Myeloperoxidase Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Caused by Antithyroid Drugs

The clinical characteristics of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis caused by antithyroid drugs are still unclear because most reports describe only a small number of patients. The objective was to analyze a large number of patients with MPO-ANCA-associated vasculitis to determine the time of onset, the drug and dose taken, the clinical symptoms, the relationship between the clinical symptoms and the MPO-ANCA titer, and the incidence. We analyzed 92 patients in whom the adverse reaction of MPO-ANCA-associated vasculitis was reported to Chugai Pharmaceutical, a company that markets antithyroid drugs. Of the 92 patients, 41 (44.6%) had single-organ failure, 32 (34.8%) had two-organ failure, 13 (14.1%), had three-organ failure, and two (2.2%) had four-organ failure. The number of organs involved was unknown in the other four patients (4.3%). The median time of onset was 42 months (range, 1-372 months) after starting drug treatment. The median dose at onset of MPO-ANCA-associated vasculitis was 15 mg/d (range, 2.5-45 mg/d) for methimazole and 200 mg/d (50-450 mg/d) for propylthiouracil. The severity and number of organs involved were not correlated with the MPO-ANCA titer. The incidence was between 0.53 and 0.79 patients per 10,000, and the ratio of the estimated incidences for methimazole and propylthiouracil was 1:39.2. The time of onset of MPO-ANCA-associated vasculitis and the dose at onset varied. The severity and number of organs involved were not correlated with the MPO-ANCA titer, indicating a need for vigilance even when the MPO-ANCA titer is only weakly positive.

A case of myeloperoxidase–antineutrophil cytoplasmic antibody positive-polyarteritis nodosa complicated by interstitial pneumonia and rapidly progressive renal failure

A 73-year-old woman was admitted to our hospital because of persistent high fever and cough, generalized myalgia, and renal dysfunction. Laboratory examination revealed severe inflammatory signs, pulmonary fibrosis, progression of renal impairment with active nephritic urinary sediments, and a high titer of myeloperoxidase-antineutrophil cytoplasmic antibody, indicating that she might have microscopic polyangiitis with interstitial pneumonia and rapidly progressive glomerulonephritis. Her renal biopsy, however, showed tubulointerstitial changes with mild glomerular abnormalities, and renal angiography revealed that she had vascular lesions of medium-sized arteries, which were compatible with classical polyarteritis nodosa. Tissue biopsy of the clinically affected organ should be considered in anyone suspected to have vasculitis.

Autopsy case of microscopic polyangiitis with crescentic glomerulonephritis and necrotizing pancreatitis

Herein is reported the case of an 84-year-old woman who initially manifested rapidly progressive glomerulonephritis following a urinary tract infection. Laboratory findings showed a high titer of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). Treatment with high-dose i.v. steroids resulted in clinical recovery and an undetectable MPO-ANCA titer. Two months later the patient was readmitted in a state of severe shock. Laboratory examination showed the deterioration of renal function, leukocytosis, and coagulation abnormalities consistent with disseminated intravascular coagulation (DIC). The patient died 12 days later. The post-mortem examination revealed necrotizing pancreatitis due to acute-stage vasculitis typified by fibrinoid necrosis of the arterioles and venules, and crescentic glomerulonephritis with healed-stage vasculitis. In the lungs, capillaritis with diffuse alveolar hemorrhage was not evident, but arteriolitis and phlebitis were occasionally seen. This case represents an unusual complication of necrotizing pancreatitis in the setting of microscopic polyangiitis. Thus, it is important to consider reactivation independent of the titer of ANCA in the course of the disease.

Neonatal microscopic polyangiitis secondary to transfer of maternal myeloperoxidase–antineutrophil cytoplasmic antibody resulting in neonatal pulmonary hemorrhage and renal involvement

Microscopic polyangiitis is a systemic vasculitis characterized by small vessel involvement. Studies suggest myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) is involved in its pathogenesis, and the titer may reflect disease activity. To report a case of transplacental transfer of MPO-ANCA from a mother to a 33-week gestational age neonate that resulted in neonatal pulmonary hemorrhage and renal involvement that was successfully treated with high-dose steroid therapy and exchange transfusion. MPO-ANCA titers from the cord blood and the neonate on the 8th, 15th, and 25th days of life (DOLs) were obtained. Metabolic panels and chest x-ray examinations were performed for the neonate and mother and the following values were measured: ANCA, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, serial urinalysis, and complete blood cell count. Anti-glomerular basement membrane, quantitative immunoglobulins, anticardiolipin antibody, and rheumatoid factor were also measured for the neonate. The neonate had elevated MPO-ANCA titers at birth. Pulmonary hemorrhage and renal involvement were seen on DOL 2. High-dose steroid therapy decreased symptoms within 1.5 hours of initiation. Exchange transfusion performed on DOL 5 removed all of the remaining MPO-ANCA by DOL 25. The child remains asymptomatic to date. To our knowledge, this is the first reported case of transplacental transfer of MPO-ANCA resulting in pulmonary-renal syndrome that was successfully treated with high-dose steroid therapy and exchange transfusion.

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.

Drug-induced MPO-ANCA-positive necrotizing crescentic glomerulonephritis preceded by granulomatous hepatitis

A 67-year-old man being treated with allopurinol, furosemide, digoxin, and tamocapril for congestive heart failure and paroxysmal atrial fibrillation was admitted to our hospital because of intermittent fever, general fatigue, and liver dysfunction. On admission, myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, and the titer was high. Discontinuation of all four drugs led to improvement of the symptoms, but the patient's renal function deteriorated. Liver biopsy showed granulomatous hepatitis (GH), and renal biopsy findings led to a diagnosis of pauci-immune necrotizing crescentic glomerulonephritis (CGN). The patient's renal function spontaneously improved without immunosuppressive therapy, and the MPO-ANCA titer decreased. We speculate that some common pathway induced by the drugs, possibly allopurinol, led to the two different clinical diseases, GH and CGN.

血管炎に関与する好中球自己抗体ＭＰＯ‐ＡＮＣＡのエピトープ

Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) has been widely detected in some diseases. It appears that the titer of MPO-ANCA is not always correlated with the activity of the disease. The epitope mapping of MPO-ANCA using recombinant proteins has been demonstrated to be effective in elucidating their etiology. The recombinant fragments of the MPO molecule have been expressed in E. coli without the association of the sugar moiety for the epitope analysis. The Western blotting and ELISA using the purified recombinant deletion mutants of human MPO has been established. It seems to be useful for sub-classifica-tion of MPO-ANCA related vasculitis. When epitope of sera of patients with MPO-ANCA-related renal diseases and vasculitis was analyzed by the Western blotting. Most of the sera reacted with either of the region of N- or C-terminus of the heavy chain, whereas no serum reacted with the light chain regions. Recently, some model mice of MPO-ANCA have been examined also.