cANCA

cANCA, or cytoplasmic anti-neutrophil cytoplasmic antibodies, refers to a specific staining pattern observed on indirect immunofluorescence testing of neutrophils using patient serum. The pattern shows diffuse, granular cytoplasmic fluorescence with relatively less staining around the nucleus, differentiating it from the pANCA pattern, which is perinuclear. In most cases, cANCA corresponds to antibodies directed against proteinase 3 (PR3), which can be detected with antigen-specific immunoassays such as ELISA or chemiluminescent assays.

Clinical relevance: cANCA with PR3 specificity is strongly associated with granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis). The presence of cANCA/PR3-ANCA supports the diagnosis in the appropriate clinical context and can correlate with active disease, but it is not universal. Some GPA patients are ANCA-negative, and PR3-ANCA can occasionally be found in conditions other than GPA. Conversely, pANCA with myeloperoxidase (MPO) specificity is more commonly linked to microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis, though patterns are not absolute.

Testing and interpretation: Routine testing often combines indirect immunofluorescence to identify the cytoplasmic pattern with antigen-specific assays for PR3-ANCA. A positive cANCA pattern coupled with PR3-ANCA supports GPA, but diagnosis remains clinical, requiring interpretation alongside symptoms, imaging, and sometimes tissue biopsy. Serologic patterns can change with disease activity and treatment.

Limitations: False positives and negatives occur. Some GPA patients may lack ANCA, and not all cANCA results reflect GPA. Advances in assay technology have improved specificity and reduced misclassification.