What are the implications of elevated myeloperoxidase (MPO) antibody levels?

From the Guidelines

Elevated myeloperoxidase (MPO) antibody levels are associated with an increased risk of autoimmune vasculitis, particularly microscopic polyangiitis, and require a comprehensive evaluation by a rheumatologist to determine the underlying diagnosis and guide treatment. The presence of MPO antibodies indicates an autoimmune process where the immune system mistakenly attacks small blood vessels, potentially causing inflammation and damage to organs like the kidneys, lungs, and skin 1.

Key Points to Consider

• MPO antibodies are autoantibodies that target the enzyme myeloperoxidase found in neutrophils, and an abnormal or positive MPO antibody test suggests the presence of anti-neutrophil cytoplasmic antibodies (ANCA) with a perinuclear staining pattern (p-ANCA) 1.
• The most frequent condition linked to elevated MPO antibodies is microscopic polyangiitis, though they can also be found in eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) and less commonly in granulomatosis with polyangiitis (formerly Wegener's granulomatosis) 1.
• Treatment depends on the specific diagnosis and may include immunosuppressive medications such as corticosteroids (prednisone), cyclophosphamide, rituximab, or azathioprine 1.
• According to the KDIGO 2024 clinical practice guideline for the management of ANCA-associated vasculitis, the diagnosis of AAV relies on the combination of clinical findings and results of imaging studies and laboratory tests, and about 90% of patients with small-vessel vasculitis or NCGN have ANCA, directed primarily to the neutrophil granule proteins MPO or PR3 1.

Implications of Elevated MPO Antibody Levels

• Elevated MPO antibody levels are associated with an increased risk of kidney disease, particularly rapidly progressive glomerulonephritis, and pulmonary hemorrhage 1.
• The presence of MPO antibodies requires a comprehensive evaluation by a rheumatologist to determine the underlying diagnosis and guide treatment, as this finding alone is not diagnostic but requires correlation with clinical symptoms, other laboratory tests, and possibly tissue biopsy 1.
• The KDIGO 2024 clinical practice guideline for the management of ANCA-associated vasculitis recommends that patients with elevated MPO antibody levels be treated with immunosuppressive medications, such as rituximab or cyclophosphamide, to induce remission and prevent relapse 1.

From the Research

Implications of Elevated Myeloperoxidase (MPO) Antibody Levels

Elevated MPO antibody levels have been associated with various clinical implications, including:

• Increased risk of relapse in patients with ANCA-associated vasculitis (AAV) 2, 3
• Higher likelihood of disease activity and poor prognosis in patients with MPO-ANCA-positive interstitial lung disease (ILD) 4
• Association with silicosis, alveolar hemorrhage, and rapidly progressive glomerulonephritis in patients with MPO-ANCA-associated vasculitis 5
• Correlation with disease extent and activity, as measured by the Birmingham vasculitis activity score and disease extent index 2

Clinical Features and Prognosis

The clinical features and prognosis of patients with elevated MPO antibody levels vary depending on the underlying disease, including:

• MPO-ANCA-positive ILD, which has different clinical features and prognoses compared to other subtypes of ILD 4
• ANCA-associated vasculitis, which has a higher risk of relapse and poor prognosis in patients with elevated MPO antibody levels 2, 3
• Silicosis, which increases the risk of developing MPO-ANCA-associated vasculitis and other complications 5

Disease Activity and Relapse

Elevated MPO antibody levels are a useful marker of disease activity and a good predictor of relapse in patients with ANCA-associated vasculitis, including:

• Increased risk of relapse in patients with elevated MPO antibody levels 2, 3
• Correlation between MPO antibody levels and disease activity, as measured by the Birmingham vasculitis activity score and disease extent index 2
• Utility of monitoring MPO antibody levels to predict relapse and guide treatment decisions 2, 3