Are Anti-Neutrophil Cytoplasmic Antibodies (ANCA)-C and ANCA-P (granulocyte cytoplasmic antibodies) indicated in Multiple Sclerosis (MS) diagnosis?

ANCA-C and ANCA-P Testing in Multiple Sclerosis

ANCA-C and ANCA-P (granulocyte cytoplasmic antibodies) testing is not indicated in the diagnosis of Multiple Sclerosis (MS) as there is no established diagnostic or clinical relevance of these antibodies in MS.

Rationale for Not Testing ANCA in MS

Limited Evidence for ANCA in MS

• ANCA testing has no established role in MS diagnosis or management according to current guidelines
• Research shows extremely low positivity rates in MS patients:
  • Only 1 out of 117 MS patients (0.9%) had c-ANCA positivity
  • Only 2 out of 117 MS patients (1.7%) had p-ANCA positivity 1
• These rates are significantly lower than what would be expected for a clinically relevant biomarker

Established Diagnostic Role of ANCA

ANCA testing has well-defined clinical applications in:

1. ANCA-Associated Vasculitides (AAV):

   • Granulomatosis with polyangiitis (GPA)
   • Microscopic polyangiitis (MPA)
   • Eosinophilic granulomatosis with polyangiitis (EGPA)
   • PR3-ANCA is detected in 80-90% of GPA patients
   • MPO-ANCA is found in 35-40% of EGPA patients 2

2. Other conditions where ANCA may be relevant:

   • Primary sclerosing cholangitis (26-96% ANCA positivity) 2
   • Inflammatory bowel disease
   • Certain autoimmune liver diseases
   • Drug-induced vasculitis

Clinical Significance of ANCA Testing

When ANCA Testing Should Be Considered

• Suspected vasculitis with symptoms such as:
  • Nasal crusting and bleeding
  • Disproportionate systemic unwellness
  • Pulmonary-renal syndrome
  • Pauci-immune glomerulonephritis 2

Proper ANCA Testing Methodology

• Current guidelines recommend:
  • Testing for both PR3-ANCA and MPO-ANCA using high-quality antigen-specific assays
  • Using immunofluorescence in combination with antigen-specific ELISAs for optimal diagnostic performance 2, 3

ANCA in Other Neurological Conditions

While ANCA testing is not indicated for MS, there are some neurological conditions where ANCA may have relevance:

• Neuromyelitis optica (NMO) spectrum disorders:

  • Higher ANCA positivity rates compared to MS (13.9% for p-ANCA, 4.2% for c-ANCA)
  • ANCA-positive NMO patients tend to be older and have longer spinal cord lesions 1

• Recurrent longitudinal extensive transverse myelitis:

  • 19% p-ANCA positivity
  • 4.8% c-ANCA positivity 1

Conclusion

ANCA testing should be directed toward conditions where it has established clinical utility. For MS diagnosis, standard diagnostic criteria including clinical presentation, MRI findings, CSF analysis, and evoked potentials remain the cornerstone of diagnosis, while ANCA testing has no established role in this disease.