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2017 ; 188
(1
): 174-181
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Immunoglobulin (Ig)M antibodies to proteinase 3 in granulomatosis with
polyangiitis and microscopic polyangiitis
#MMPMID28076879
Clain JM
; Hummel AM
; Stone JH
; Fervenza FC
; Hoffman GS
; Kallenberg CG
; Langford CA
; McCune WJ
; Merkel PA
; Monach PA
; Seo P
; Spiera RF
; St Clair EW
; Ytterberg SR
; Specks U
Clin Exp Immunol
2017[Apr]; 188
(1
): 174-181
PMID28076879
show ga
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.