Anti-Neutrophil Cytoplasmic Antibodies (ANCA)

Overview

Anti-Neutrophil Cytoplasmic Antibodies (ANCA) are autoantibodies produced by the immune system that mistakenly target proteins present inside neutrophils. As described in the document, these antibodies play a key role in the development of autoimmune vasculitis, a group of disorders characterized by inflammation and damage of small blood vessels. ANCA-associated vasculitides are relatively rare autoimmune conditions of unknown cause and are marked by inflammatory cell infiltration leading to necrosis of vessel walls.

ANCA is considered an important serological marker of vasculitis and is widely used for diagnosis, classification, and monitoring of disease activity. The two main ANCA patterns include c-ANCA, which targets proteinase-3 (PR3), and p-ANCA, which targets myeloperoxidase (MPO). Identifying the ANCA type helps clinicians determine the specific form of autoimmune vasculitis and assess organ involvement, such as the kidneys, lungs, upper airways, and nervous system.

Symptoms

Symptoms associated with ANCA positivity arise from systemic inflammation and blood vessel injury rather than from the antibodies themselves. The document lists several common presenting symptoms seen in ANCA-associated autoimmune conditions.

General symptoms include:

1. Fatigue and malaise
2. Fever
3. Loss of appetite
4. Weight loss
5. Generalized body aches

Musculoskeletal and skin symptoms may include:

1. Joint pain, stiffness, and swelling
2. Muscle weakness
3. Skin rashes
4. Photosensitivity
5. Hair loss
6. Skin thickening or tightening

Other systemic features include:

1. Oral ulcers
2. Swollen lymph nodes
3. Raynaud’s phenomenon, with color changes in fingers or toes
4. Dry eyes and dry mouth, especially when overlapping with Sjögren’s syndrome

Depending on the type of vasculitis, symptoms may also involve respiratory tract issues, kidney dysfunction, or neurological manifestations. These symptoms often prompt ANCA testing to identify autoimmune vasculitis and assess disease severity.

Causes

The document explains that ANCA formation results from immune dysregulation and abnormal activation of white blood cells.

Key causes include:

1. Autoimmune response, where the immune system targets neutrophil components
2. Activation of neutrophils and monocytes, triggered by ANCA binding
3. Release of destructive enzymes, reactive oxygen species, and neutrophil extracellular traps, leading to vascular injury
4. Endothelial cell damage, resulting in inflammation and necrosis of blood vessels
5. Complement pathway activation, which amplifies inflammatory damage

Microbial infections are described as potential triggers that prime neutrophils, allowing ANCA to interact with them and initiate the inflammatory cascade. This immune-mediated damage forms the foundation of ANCA-associated vasculitis.

Risk Factors

Risk factors for ANCA positivity are associated with autoimmune conditions, inflammatory diseases, and clinical scenarios that require vasculitis evaluation.

Key risk factors include:

1. Suspected or confirmed autoimmune vasculitis
2. Symptoms involving the kidneys, lungs, ENT region, or nervous system
3. Chronic inflammatory conditions such as inflammatory bowel disease
4. Unexplained systemic symptoms like fever, fatigue, and weight loss
5. Prior history of autoimmune disorders
6. Clinical suspicion of granulomatosis with polyangiitis, microscopic polyangiitis, or eosinophilic granulomatosis with polyangiitis
7. Patients undergoing evaluation for disease relapse or treatment response

The document also notes that atypical ANCA patterns may be seen in drug-induced vasculitides and other autoimmune diseases, making clinical correlation essential.

Prevention

ANCA formation itself cannot be prevented, as it originates from autoimmune mechanisms. However, the document outlines preventive strategies aimed at early detection, accurate testing, and complication reduction.

Preventive considerations include:

1. Early evaluation of symptoms, allowing timely identification of autoimmune vasculitis
2. No special patient preparation, enabling prompt testing when symptoms arise
3. Correct sample collection, using 3.0 ml of blood collected in a plain red-capped tube with early serum separation
4. Appropriate laboratory methods, such as immunofluorescence and ELISA, should be used to ensure accurate detection
5. Monitoring disease activity, where ANCA levels help assess response to therapy and detect relapse
6. Clinical correlation, ensuring results are interpreted alongside symptoms, imaging, and other laboratory findings
7. Avoiding misdiagnosis, as ANCA results alone do not confirm or exclude disease

Early diagnosis and consistent monitoring help reduce organ damage, guide immunosuppressive therapy, and improve long-term outcomes in ANCA-associated conditions.