What is MPO (myeloperoxidase) in rheumatology?

What is MPO in Rheumatology?

MPO (myeloperoxidase) is a neutrophil enzyme that serves as a critical autoantigen in ANCA-associated vasculitis, with antibodies against MPO (MPO-ANCA) being the primary diagnostic marker for microscopic polyangiitis and a key indicator of small-vessel vasculitis requiring urgent immunosuppressive therapy. 1

Biochemical Identity

MPO is a cationic heme-containing peroxidase enzyme located in the primary azurophilic granules of neutrophils and monocytes. 2, 3 It catalyzes the production of hypochlorous acid (HOCl) from hydrogen peroxide and chloride ions, which normally functions as part of the antimicrobial defense system. 2, 4

Diagnostic Significance in Vasculitis

MPO antibodies (MPO-ANCA) are the defining serologic marker for ANCA-associated vasculitis, particularly microscopic polyangiitis (MPA). 1 The diagnostic framework includes:

• MPO-ANCA positivity is found in approximately 70% of microscopic polyangiitis cases, making it the most common ANCA pattern in this disease. 1, 2
• High-quality antigen-specific immunoassays (ELISA) are the preferred screening method for detecting MPO-ANCA, as recommended by international consensus guidelines. 1
• About 90% of patients with small-vessel vasculitis or necrotizing crescentic glomerulonephritis have ANCA (either MPO or PR3), though 10% remain ANCA-negative. 1

Disease Associations

MPO-ANCA positivity occurs across multiple ANCA-associated vasculitides with varying frequencies:

• Microscopic polyangiitis (MPA): 70% MPO-ANCA positive, representing the primary association. 1, 2
• Eosinophilic granulomatosis with polyangiitis (EGPA): 26-48% overall MPO-ANCA positive, increasing to 75% with renal involvement. 1
• Granulomatosis with polyangiitis (GPA): Occasionally MPO-ANCA positive, though PR3-ANCA is more typical. 1
• Pauci-immune necrotizing crescentic glomerulonephritis: 20-40% of cases show MPO-ANCA positivity. 5

Clinical Phenotype

MPO-ANCA positivity predicts a specific clinical pattern distinct from PR3-ANCA disease. 5 Key manifestations include:

• Rapidly progressive glomerulonephritis with microscopic hematuria, dysmorphic red blood cells, red cell casts, and moderate proteinuria (1-3 g/day). 1, 5
• Pulmonary-renal syndrome with alveolar hemorrhage in approximately 10% of cases. 5
• Peripheral neuropathy and mononeuritis multiplex are common extrarenal manifestations. 5
• Palpable purpura indicating small-vessel vasculitis. 1, 5

Critical Clinical Decision Point

When MPO-ANCA serology is positive in combination with a clinical presentation compatible with small-vessel vasculitis, immunosuppressive therapy should be initiated immediately without waiting for kidney biopsy results, especially in rapidly deteriorating patients. 1 This represents a fundamental departure from traditional diagnostic algorithms and reflects the high specificity of MPO-ANCA testing combined with the life-threatening nature of untreated disease.

Prognostic Implications

MPO-ANCA patients have significantly lower relapse rates compared to PR3-ANCA patients, which fundamentally alters maintenance therapy decisions. 5 Specifically:

• MPO-AAV patients on dialysis without extrarenal manifestations have such low relapse risk that maintenance immunosuppression may not be warranted, as the treatment risks may outweigh benefits. 5
• This contrasts sharply with PR3-ANCA disease, where relapse rates are substantially higher and prolonged maintenance therapy is typically required. 5

Pathophysiologic Role

Beyond serving as an autoantigen, MPO-ANCA antibodies appear to have direct pathogenic effects. Anti-MPO antibodies can trigger MPO release from neutrophils and monocytes, activate the enzyme to generate oxidative stress, and produce hypochlorous acid that damages endothelium. 2 This oxidative burst leads to severe endothelial injury and perpetuates the vasculitic process. 2

Diagnostic Testing Algorithm

When MPO-ANCA-associated vasculitis is suspected, the following immediate workup is essential:

• Order antigen-specific immunoassays (ELISA) for both MPO-ANCA and PR3-ANCA simultaneously. 1, 5
• Perform urinalysis with microscopy looking specifically for dysmorphic RBCs, RBC casts, and quantify proteinuria. 5
• Assess renal function using GFR estimating equations. 5
• Consider tissue biopsy (kidney biopsy has 91.5% diagnostic yield in GPA) for definitive diagnosis, but do not delay treatment if clinical picture and serology are compelling. 1, 5

Common Pitfall

A negative ANCA does not exclude ANCA-associated vasculitis. 1 Approximately 10% of patients with MPA and up to 60% of EGPA patients are ANCA-negative, yet they are treated identically to ANCA-positive patients. 1 The diagnosis relies on the combination of clinical findings, imaging, laboratory tests, and ideally histopathology—not serology alone. 1

budget:token_budget Tokens used this turn: 0 (included in context) + 1500 (response) = 1500 Tokens used total: 1500 / 200000