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Autoantibodies to Proteinase 3 and Myeloperoxidase in Systemic Sclerosis

AMELIA RUFFATTI, RENATO ALBERTO SINICO, ANTONELLA RADICE, ELENA OSSI, FRANCO COZZI, MARTA TONELLO, PANAGIOTIS GRYPIOTIS, and SILVANO TODESCO

ABSTRACT.

Objective.
We evaluated the prevalence and clinical significance of proteinase 3 (PR3-) and myeloperoxidase (MPO-) antineutrophil cytoplasmic antibodies (ANCA) in 115 patients with systemic sclerosis (SSc, scleroderma).

Methods. Sera were assayed by 2 independent centers, which used indirect immunofluorescence (IIF) and direct ELISA as screening tests. Inhibition-ELISA for PR3- and MPO-ANCA and PR3 capture-ELISA experiments were also performed. The clinical features of the ANCA positive were compared with those of the ANCA negative scleroderma patients.

Results. The IIF test revealed 5 P-ANCA positive sera (4.34%). Surprisingly, by ELISA 2 of these were PR3-ANCA positive, one was MPO-ANCA positive, and 2 were both PR3- and MPO-ANCA positive. In addition, 3 IIF negative sera were ELISA positive, 2 for PR3- and one for MPO-ANCA. ELISA results were confirmed by fluid phase inhibition experiments. Only 2 out of the 6 PR3-direct ELISA positive sera were positive by PR3-capture ELISA at low titers. Neither PR3- nor MPO-ANCA were significantly associated to any clinical feature of patients with SSc.

Conclusion. As well as the previously described MPO-ANCA, even PR3-ANCA may be detected in some sera from patients with SSc. The IIF pattern and the negative results obtained with PR3-capture ELISA suggest that different epitopes from those recognized by vasculitis sera might be involved with PR3-ANCA in SSc, and show the importance of combining IIF and ELISA tests for ANCA detection. (J Rheumatol 2002;29:918-23)

Key Indexing Terms:

ANTIBODIES TO PROTEINASE 3
ANTIBODIES TO MYELOPEROXIDASE
ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES
SYSTEMIC SCLEROSIS


From the Department of Medical and Surgical Sciences, Division of Rheumatology and I Chair of Internal Medicine, University of Padova, Padova; and the Renal Unit and Center of Clinical Immunology, San Carlo Borromeo Hospital, Milano, Italy.

A. Ruffatti, MD, Assistant Professor of Rheumatology; R.A. Sinico, MD, Assistant Professor of Nephrology; A. Radice, PhD, Research Biologist; E. Ossi, MD, Associate Professor of Internal Medicine; F. Cozzi, MD, Assistant Professor of Rheumatology; M. Tonello, PhD, Research Biologist; P. Grypiotis, PhD, Research Fellow; S. Todesco, MD, Professor of Rheumatology.

Address reprint requests to Dr. A. Ruffatti, Divisione di Reumatologia, Policlinico Universitario, Via Giustiniani 2, 35128 Padova, Italy. E-mail: amelia.ruffatti@unipd.it

Submitted May 28, 2001; revision accepted November 30, 2001.




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