Incidence of PR3- and MPO-ANCA autoantibody specificity changes in ANCA-associated vasculitis.
BACKGROUND
Monitoring of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in remission usually includes indirect immunofluorescence (IIF), proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA. Typically, PR3 and MPO-ANCA are both performed because patients sometimes switch specificity during follow up. Published data are limited to case reports and incidence of change is not reported. The aim of this study was to quantify the incidence of antibody switching.


METHODS
Hull and East Yorkshire Hospitals National Health Service Trust serves a population of 720,000 for ANCA testing. We reviewed all ANCA results from January 2000 to August 2012 to quantify incidence of antibody switching. A total of 22,002 IIF screens (14,518 patients) were performed. A total of 9838 (45%) also had PR3- and MPO-ANCA (6439, 44% of patients). Patients that changed specificity from PR3- to MPO-ANCA and vice versa were identified and case notes reviewed.


RESULTS
A total of 218 patients with confirmed AAV positive for PR3/MPO-ANCA were followed for a mean of 2.6 years (range <0.1 to 12.4 years; with 113 (52%) patients followed for >1 year). Five patients (2%) changed specificity during follow up (3 GPA, 1 MPA & 1 EGPA). In two patients this was associated with relapse. Incidence of specificity change was 1 per 82 years (including two reversions to presenting specificity) and one per 286 years for changes associated with relapse. Monitoring using only the initial antibody specificity would have resulted in missed relapse in one patient.


CONCLUSIONS
Antibody specificity changes in AAV are rare. Monitoring only the initial antibody specificity would have missed clinical events but rising C-reactive protein presaged relapse in these cases.
Immunology Department, Hull Royal Infirmary, Hull, UK steve.holding@hey.nhs.uk.
Stephen
S
Holding
Hull York Medical School, Hull, UK.
Victoria J
VJ
Fisher
Immunology Department, Hull Royal Infirmary, Hull, UK.
Mohamed
M
Abuzakouk
D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000453:epidemiology / Q000276:immunology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis*; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D053146:Myeloblastin / Q000037:antagonists & inhibitors*; D012008:Recurrence; D012189:Retrospective Studies; D006113:United Kingdom / Q000453:epidemiology; D015854:Up-Regulation
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D002097:C-Reactive Protein; D053146:Myeloblastin
ANCA; ANCA associated vasculitis; eosinophilic granulomatous polyangiitis; granulomatous polyangiitis; microscopic polyangiitis; vasculitis