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Anticytoplasmic Autoantibodies: Their Immunodiagnostic Value in Wegener Granulomatosis

Bernhard Nolle, MD; Ulrich Specks, MD; Jens Lüdemann, MS; Michael S. Rohrbach, PhD; Richard A. DeRemee, MD; and Wolfgang L. Gross, MD
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Grant Support: Supported in part by grant 01 VM 8622 from Bundesminister für Forschung und Technologie, Deutsche Forschungsgemeinschaft (DFG) Gr 609/4-3, and Verein zur Bekämpfung und Erforschung rheumatischer Erkrankungen e.V., Bad Bramstedt, Federal Republic of Germany.

Requests for Reprints: Prof. Dr. Wolfgang L. Gross, Abtlg. Allgemeine Innere Medizin, I. Medizinische Klinik, Klinikum der Christian-Albrechts-Universität, Schittenhelmstrasse 12, D-2300 Kiel, Federal Republic of Germany.

Current Author Addresses: Dr. Nölle: Zentrum Operative Medizin II, Abtlg. Ophthalmologie, Klinikum der Christian-Albrechts-Universität, Hegewischstrasse 2, D-2300 Kiel, Federal Republic of Germany. Drs. Specks, Rohrbach, and DeRemee: Division of Thoracic Diseases and Internal Medicine, Mayo Clinic and Foundation, 200 First Street, Rochester, MN 55905, USA. Dr. Gross and Mr. Lüdemann: Abtlg. Allgemeine Innere Medizin, I. Medizinische Klinik, Klinikum der Christian-Albrechts-Universität, Schittenhelmstrasse 12, D-2300 Kiel, Federal Republic of Germany.

© 1989 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1989;111(1):28-40. doi:10.7326/0003-4819-111-1-28
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Study Objective: To determine disease specificity and sensitivity of anticytoplasmic autoantibodies (ACPA) for Wegener granulomatosis, as well as their value as a marker of disease activity.

Design: Blind analysis of serum samples, retrospective analysis of clinical data on patients, and prospective follow-up of a subgroup of patients with Wegener granulomatosis.

Patients: The study included 277 patients with Wegener granulomatosis (222 with biopsy-proven disease) and 1657 control patients.

Setting: University hospital and academic medical center.

Laboratory Investigations: Analysis of 2653 serum samples from 1934 patients for ACPA. Antibody detection was by indirect immunofluorescence and a new type of enzyme-linked immunoadsorbent assay (ELISA). Prospective follow-up was on 172 patients with Wegener granulomatosis.

Measurements and Main Results: Specificity of ACPA for Wegener granulomatosis measured by indirect immunofluorescence was 99% (CI, 98.9% to 99.7%) and 98% (CI, 97.4% to 99.2%) by ELISA. Sensitivity of ACPA depended on disease activity and extent: It was 67% (CI, 38% to 89%) by immunofluorescence and 60% (CI, 32% to 84%) by ELISA for patients with active locoregional symptomatology (n = 15); and 32% (CI, 14% to 54%) by immunofluorescence and 40% (CI, 21% to 61%) by ELISA for patients in full remission after initial locoregional symptoms (n = 25). The sensitivity was 96% (CI, 89% to 99%) by immunofluorescence and 93% (CI, 86% to 98%) by ELISA for patients with active generalized disease (n = 92). Serial testing was done; every patient with active generalized disease eventually had at least one positive serum sample. Sensitivity decreased to 41% (CI, 22% to 62%) by both immunofluorescence and ELISA for patients in full remission after active generalized disease (n = 27). Levels of ACPA expressed both as immunofluorescence titers and ELISA values (U/mL) correlated well with disease activity.

Conclusions: Testing for ACPA in serum of patients with Wegener granulomatosis is valuable for differential diagnosis; furthermore, APCA can be used as a marker to follow disease activity. A new type of ELISA yielded the same results as indirect immunofluorescence for the specificity, sensitivity, and correlation with disease activity of ACPA.





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