Immunoglobulin (Ig)M antibodies to proteinase 3 in granulomatosis with polyangiitis and microscopic polyangiitis

for the WGET and RAVE-ITN Research Groups

Research output: Contribution to journalArticle

4 Citations (Scopus)

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%, P50·10). 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.

Original languageEnglish (US)
Pages (from-to)174-181
Number of pages8
JournalClinical and Experimental Immunology
Volume188
Issue number1
DOIs
StatePublished - Apr 1 2017

Fingerprint

Microscopic Polyangiitis
Myeloblastin
Granulomatosis with Polyangiitis
Immunoglobulin M
Antineutrophil Cytoplasmic Antibodies
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Antibodies
Hemorrhage
Immunoglobulin Isotypes

Keywords

  • Alveolar haemorrhage
  • ANCA-associated vasculitis
  • Anti-neutrophil cytoplasmic antibodies
  • Granulomatosis with polyangiitis
  • Immunoglobulin M
  • Microscopic polyangiitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Immunoglobulin (Ig)M antibodies to proteinase 3 in granulomatosis with polyangiitis and microscopic polyangiitis. / for the WGET and RAVE-ITN Research Groups.

In: Clinical and Experimental Immunology, Vol. 188, No. 1, 01.04.2017, p. 174-181.

Research output: Contribution to journalArticle

@article{e996d9b92cca4ade9feb87fd078da503,
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{\%}, P50·10). 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.",
keywords = "Alveolar haemorrhage, ANCA-associated vasculitis, Anti-neutrophil cytoplasmic antibodies, Granulomatosis with polyangiitis, Immunoglobulin M, Microscopic polyangiitis",
author = "{for the WGET and RAVE-ITN Research Groups} and Clain, {J. M.} and Hummel, {A. M.} and Stone, {J. H.} and Fervenza, {Fernando Custodio} and Hoffman, {G. S.} and Kallenberg, {C. G M} and Langford, {C. A.} and McCune, {W. J.} and Merkel, {P. A.} and Monach, {P. A.} and P. Seo and Spiera, {R. F.} and {St Clair}, {E. W.} and Ytterberg, {Steven R} and Ulrich Specks",
year = "2017",
month = "4",
day = "1",
doi = "10.1111/cei.12925",
language = "English (US)",
volume = "188",
pages = "174--181",
journal = "Clinical and Experimental Immunology",
issn = "0009-9104",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Immunoglobulin (Ig)M antibodies to proteinase 3 in granulomatosis with polyangiitis and microscopic polyangiitis

AU - for the WGET and RAVE-ITN Research Groups

AU - Clain, J. M.

AU - Hummel, A. M.

AU - Stone, J. H.

AU - Fervenza, Fernando Custodio

AU - Hoffman, G. S.

AU - Kallenberg, C. G M

AU - Langford, C. A.

AU - McCune, W. J.

AU - Merkel, P. A.

AU - Monach, P. A.

AU - Seo, P.

AU - Spiera, R. F.

AU - St Clair, E. W.

AU - Ytterberg, Steven R

AU - Specks, Ulrich

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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%, P50·10). 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.

AB - 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%, P50·10). 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.

KW - Alveolar haemorrhage

KW - ANCA-associated vasculitis

KW - Anti-neutrophil cytoplasmic antibodies

KW - Granulomatosis with polyangiitis

KW - Immunoglobulin M

KW - Microscopic polyangiitis

UR - http://www.scopus.com/inward/record.url?scp=85012928606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85012928606&partnerID=8YFLogxK

U2 - 10.1111/cei.12925

DO - 10.1111/cei.12925

M3 - Article

C2 - 28076879

AN - SCOPUS:85012928606

VL - 188

SP - 174

EP - 181

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

SN - 0009-9104

IS - 1

ER -