What is the significance of myeloperoxidase (MPO) antibodies?

Significance of MPO Antibodies

MPO (myeloperoxidase) antibodies are autoantibodies that indicate ANCA-associated vasculitis, particularly microscopic polyangiitis, and serve as both a diagnostic marker and disease activity monitor, with critical implications for identifying patients at risk for life-threatening glomerulonephritis and pulmonary hemorrhage. 1

Diagnostic Significance

MPO-ANCA positivity establishes the diagnosis of small-vessel vasculitis when combined with compatible clinical features, allowing immediate initiation of immunosuppressive therapy without waiting for biopsy confirmation, especially in rapidly deteriorating patients. 1, 2

Disease Associations

• MPO antibodies are detected in 35-40% of patients with microscopic polyangiitis (MPA), making it the most common ANCA-associated vasculitis linked to MPO positivity 1
• Present in 35% of eosinophilic granulomatosis with polyangiitis (EGPA) patients, typically those with more renal involvement 1, 3
• Approximately 5-10% of granulomatosis with polyangiitis (GPA) cases show MPO-ANCA rather than the typical PR3-ANCA 3
• Detected in pauci-immune necrotizing crescentic glomerulonephritis in 20-40% of cases 1

Clinical Phenotype

MPO-ANCA positivity predicts a specific clinical pattern:

• Rapidly progressive glomerulonephritis with microscopic hematuria, dysmorphic red blood cells, red cell casts, and moderate proteinuria (1-3 g/day) 1, 2, 3
• Pulmonary-renal syndrome with alveolar hemorrhage in 10% of cases, significantly increasing mortality risk 2
• Peripheral neuropathy and mononeuritis multiplex 2
• Palpable purpura indicating dermal small-vessel vasculitis 2

Prognostic and Treatment Implications

Relapse Risk Stratification

MPO-ANCA patients have significantly lower relapse rates compared to PR3-ANCA patients, which fundamentally alters maintenance therapy decisions. 1

• In MPO-AAV patients on dialysis without extrarenal manifestations, the relapse risk is so low that maintenance immunosuppression risks may outweigh benefits 1
• MPO-AAV patients achieving complete clinical remission with abnormal kidney function may be managed with close monitoring and regular ANCA serologies rather than maintenance immunosuppression 1
• However, even patients on kidney replacement therapy with extrarenal AAV manifestations require maintenance therapy as extrarenal disease can and does relapse 1

Disease Activity Monitoring

Serial MPO-ANCA titers correlate with disease activity and decrease following effective therapy, making them useful for monitoring treatment response. 4, 3

• Titers should be interpreted alongside clinical findings (CRP, ESR, urinalysis) rather than as standalone markers, as approximately 10% of AAV patients can have negative inflammatory markers despite active disease 2
• Sequential ANCA monitoring can predict relapse in some patients, though not all show this pattern 3

Diagnostic Testing Algorithm

When MPO antibodies are suspected:

1. Order antigen-specific immunoassays (ELISA) for both MPO-ANCA and PR3-ANCA immediately - this is the preferred screening method over indirect immunofluorescence 1, 2, 3
2. Obtain urinalysis with microscopy looking for dysmorphic RBCs, RBC casts, and quantify proteinuria 2
3. Assess renal function using GFR estimating equations 2
4. Consider tissue biopsy (kidney has 91.5% diagnostic yield in GPA) for definitive diagnosis 1, 2
5. Start immunosuppressive therapy immediately without waiting for biopsy if clinical presentation is compatible with small-vessel vasculitis and MPO-ANCA is positive, especially in rapidly deteriorating patients 1, 2

Critical Pitfalls

MPO antibodies are not specific to vasculitis alone - they can be detected in:

• Autoimmune hepatitis, primary sclerosing cholangitis, and inflammatory bowel disease 3
• Systemic lupus erythematosus (typically low titers compared to high titers in vasculitis) 4
• Rheumatoid arthritis 4
• Drug-induced vasculitis (particularly propylthiouracil), where antibodies may recognize more restricted epitopes 1, 5

Approximately 10% of patients with clinical AAV are persistently ANCA-negative, requiring treatment based on clinical and histologic findings alone. 1, 2

MPO-ANCA can be present in interstitial lung disease without systemic vasculitis, requiring monitoring for development of ANCA-associated vasculitis but potentially different treatment approaches. 6