title: Myeloperoxidase-antineutrophil Cytoplasmic Antibodies (MPO-ANCA) and Proteinase 3-ANCA without Immunofluorescent ANCA Found by Routine Clinical Testing.
abstract: OBJECTIVE
  Concurrent testing for serum antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IF) and by antiproteinase 3 (PR3)/antimyeloperoxidase (MPO) antibody assays may identify patients with PR3-ANCA or MPO-ANCA despite a negative IF (IF-negative MPO/PR3-positive); however, the significance of this result is not clear. We sought to determine whether IF-negative, MPO/PR3-positive results identified any cases of clinically meaningful systemic vasculitis at our institution.
  
  
  METHODS
  We conducted a retrospective chart review of all IF-negative, MPO/PR3-positive patients identified at our institution over a 2-year period.
  
  
  RESULTS
  Of the 2345 samples tested over 2 years, 1998 were IF-negative. Among these IF-negative samples, 49 samples (2.5%) derived from 38 patients tested positive for MPO-ANCA or PR3-ANCA. Only 1 IF-negative, MPO/PR3-positive patient was subsequently diagnosed with ANCA-associated vasculitis (AAV). Eleven IF-negative, MPO/PR3-positive patients (29%) had been previously diagnosed and treated for AAV, all with positive IF and antibody tests prior to treatment. Four patients had evidence of cutaneous vasculitis not attributed to AAV, while several of the remaining IF-negative, MPO/PR3-positive patients had other immunologic disorders, including systemic lupus erythematosus (5 patients) and inflammatory bowel disease (3 patients).
  
  
  CONCLUSIONS
  In this real-life cohort assayed simultaneously by IF and multiplexed bead assays, the detection of MPO-ANCA or PR3-ANCA without a positive IF rarely led to a new diagnosis of systemic vasculitis, and was more likely to occur in the context of a non-vasculitic inflammatory condition. Our results suggest that concurrent IF and MPO/PR3 testing may be of limited use in preventing a missed diagnosis of new-onset AAV.
authors.affiliation: From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School.
authors.forename: Deepak A
authors.initials: DA
authors.lastname: Rao
authors.affiliation: From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School.
authors.forename: Kevin
authors.initials: K
authors.lastname: Wei
authors.affiliation: From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Merola
authors.affiliation: From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School.
authors.forename: William R
authors.initials: WR
authors.lastname: O'Brien
authors.affiliation: From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School.
authors.forename: Samuel U
authors.initials: SU
authors.lastname: Takvorian
authors.affiliation: From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School. pschur@partners.org pdellaripa@partners.org.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Dellaripa
authors.affiliation: From the Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital; Harvard Medical School, Boston, Massachusetts, USA.D.A. Rao, MD, PhD, Fellow in Rheumatology; K. Wei, MD, PhD, Fellow in Rheumatology; W.R. O'Brien, Fellow in Rheumatology; S.U. Takvorian, MD, Resident in Internal Medicine; P.F. Dellaripa, MD, Assistant Professor of Medicine; P.H. Schur, MD, Professor of Medicine, Brigham and Women's Hospital; J.F. Merola, MD, Instructor, Harvard Medical School. pschur@partners.org pdellaripa@partners.org.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Schur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology*; D009195:Peroxidase / Q000276:immunology*; D012189:Retrospective Studies; D056647:Systemic Vasculitis / Q000175:diagnosis* / Q000276:immunology; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D009195:Peroxidase; D053146:Myeloblastin
keywords: ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; OUTCOMES; VASCULITIS
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