title: Immunoglobulin (Ig)M antibodies to proteinase 3 in granulomatosis with polyangiitis and microscopic polyangiitis.
abstract: Anti-neutrophil cytoplasmic antibodies (ANCA) appear to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). However, ANCA alone are not sufficient to generate disease, and some evidence suggests that infectious triggers may serve as inciting events for AAV disease activity. Antibodies of the immunoglobulin (Ig)M isotype often serve as markers of recent infection, and IgM ANCA have been identified previously in patients with AAV, although the frequency and clinical relevance of IgM ANCA is not well established. We sought to characterize IgM ANCA more clearly by creating a novel enzyme-linked immunosorbent assay (ELISA) for IgM antibodies to proteinase 3 [IgM proteinase 3 (PR3)-ANCA], which we applied to two large, clinically well-characterized trial cohorts of patients with granulomatosis with polyangiitis and microscopic polyangiitis. In the first cohort, IgM PR3-ANCA occurred with a frequency of 15·0%, and were associated with a higher degree of disease severity and a trend towards a higher rate of alveolar haemorrhage (29·6 versus 15·7%, P = 0·10). Analysis of follow-up samples in this cohort showed that the presence of IgM PR3-ANCA was transient, but could recur. In the second cohort, IgM PR3-ANCA occurred with a frequency of 41·1%, and were also associated with a higher degree of disease severity. A higher rate of alveolar haemorrhage was observed among those with IgM PR3-ANCA (45·3 versus 15·8%; P < 0·001). The association of transient IgM PR3-ANCA with an acute respiratory manifestation of AAV suggests a possible link between an infectious trigger and AAV disease activity.
authors.affiliation: Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Clain
authors.affiliation: Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Hummel
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Stone
authors.affiliation: Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: F C
authors.initials: FC
authors.lastname: Fervenza
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Hoffman
authors.affiliation: University of Groningen, Groningen, the Netherlands.
authors.forename: C G M
authors.initials: CG
authors.lastname: Kallenberg
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Langford
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: McCune
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Merkel
authors.affiliation: Boston University Medical Center, Boston, MA, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Monach
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Seo
authors.affiliation: Hospital for Special Surgery, New York, NY, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Spiera
authors.affiliation: Duke University, Durham, NC, USA.
authors.forename: E W
authors.initials: EW
authors.lastname: St Clair
authors.affiliation: Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Ytterberg
authors.affiliation: Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: U
authors.initials: U
authors.lastname: Specks
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D008297:Male; D055953:Microscopic Polyangiitis / Q000175:diagnosis / Q000276:immunology*; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology*; D012720:Severity of Illness Index
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D053146:Myeloblastin
keywords: ANCA-associated vasculitis; alveolar haemorrhage; anti-neutrophil cytoplasmic antibodies; granulomatosis with polyangiitis; immunoglobulin M; microscopic polyangiitis