What is the clinical association between ANCA and GPA?
The following statements can be made about the clinical association between ANCA and GPA:
Sensitivity and specificity: ANCA positivity is seen in 90% of patients with active, generalized GPA, whereas only 60% of patients with limited GPA are ANCA-positive, yielding an overall sensitivity of 73%. Among GPA patients with positive ANCA, 80% to 90% are c-ANCA-positive with PR3 specificity, whereas 10% to 20% are p-ANCA-positive with MPO specificity. The overall specificity of PR3-ANCA for active generalized GPA is 98%.
ANCA titers and disease flares (controversial): conflicting data exists in the literature regarding the utility of ANCA titers (either increases in titer or transition from a negative to positive status) to predict subsequent flares of GPA. Some studies suggest that by limiting the target population (PR3-positive GPA patients with vasculitic manifestations), the utility of following serial ANCA measurements can be improved. In addition, some experts believe that in patients treated with rituximab who subsequently become c-ANCA/PR3-negative, absence of antibody coupled with undetectable B-cell counts is associated with a low risk of flare. Nonetheless, a large randomized trial of scheduled rituximab treatment versus retreatment based on rising ANCA titers and/or B-cell counts failed to demonstrate an association between ANCA titers and subsequent clinical flare (although interestingly the as-needed retreatment strategy had roughly equivalent clinical outcomes with decreased drug exposure). Based upon the existing data, prophylactic increases in immunosuppressive medications should not be instituted in a patient with a rising ANCA titer unless the patient exhibits clinical signs of disease exacerbation. Notably, ANCA titers do not tend to rise during an acute infection, which may aid in distinguishing exacerbation of GPA from an infectious process in patients with previously quiescent disease.
