From the Guidelines
A positive p-ANCA with negative MPO antibodies suggests an atypical ANCA pattern that may be associated with inflammatory bowel disease, primary sclerosing cholangitis, autoimmune hepatitis, or drug-induced vasculitis rather than classic ANCA-associated vasculitis. This pattern occurs because p-ANCA can target other neutrophil proteins besides MPO, such as lactoferrin, elastase, cathepsin G, or BPI (bactericidal/permeability-increasing protein) 1. When evaluating this finding, it's essential to consider the complete clinical picture, including symptoms, other laboratory results, and imaging studies, rather than relying solely on this antibody pattern 1. Additional testing may be needed, such as tissue biopsy, comprehensive autoimmune panels, or gastrointestinal evaluation 1. The distinction is clinically significant because treatment approaches differ substantially between ANCA-associated vasculitis (which typically requires immunosuppression with cyclophosphamide or rituximab) and conditions associated with atypical p-ANCA patterns, which may require disease-specific therapies. Some key points to consider in the management of patients with positive p-ANCA and negative MPO antibodies include:
- The presence of ANCA is not diagnostic on its own and should be considered in the context of clinical symptoms and other laboratory findings 1
- The pattern of ANCA positivity can help guide the diagnosis, but additional testing is often necessary to confirm the diagnosis 1
- Treatment should be tailored to the specific condition and may involve immunosuppression, disease-modifying antirheumatic drugs (DMARDs), or other therapies 1
- Regular monitoring and follow-up are essential to assess disease activity and adjust treatment as needed 1.
From the Research
Definition of p-ANCA and MPO Antibodies
- p-ANCA (perinuclear anti-neutrophil cytoplasmic antibodies) refers to a pattern of staining seen in indirect immunofluorescence assays, where the antibodies target antigens in the perinuclear region of neutrophils 2.
- MPO (myeloperoxidase) antibodies are a type of ANCA that targets the myeloperoxidase enzyme in neutrophils, and are often associated with microscopic polyangiitis (MPA) and other forms of vasculitis 2, 3.
Clinical Significance of Positive p-ANCA with Negative MPO Antibodies
- A positive p-ANCA result with negative MPO antibodies may indicate the presence of other ANCA-specificities, such as PR3-ANCA (protease 3-ANCA) 2, 4.
- However, the clinical significance of this result is not always clear, and may require further evaluation and testing to determine the underlying cause 4.
- In some cases, a positive p-ANCA result with negative MPO antibodies may be associated with non-vasculitic inflammatory conditions, such as systemic lupus erythematosus or inflammatory bowel disease 4.
Diagnostic and Treatment Implications
- The diagnosis of ANCA-associated vasculitis (AAV) typically requires a combination of clinical, laboratory, and imaging findings, including the presence of ANCA antibodies 2, 5, 6.
- Treatment of AAV often involves immunosuppressive therapy, such as rituximab, cyclophosphamide, and glucocorticoids, and may require plasma exchange in severe cases 5, 6.
- The presence of p-ANCA with negative MPO antibodies may influence the choice of treatment and require closer monitoring for the development of vasculitis or other complications 2, 3.