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Article Review/Hyperlink
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Merkel PA, Polisson RP, Chang YX, Skates SJ, Niles JL
Prevalence of antineutrophil cytoplasmic antibodies in a large
inception cohort of patients with connective tissue diseases
Ann Int Med
(Jun) 126:866-873 1997

Antineutrophil cytoplasmic antibodies (ANCA) against proteinase 3
(C-ANCA) and
myeloperoxidase (P-ANCA) are hallmarks of vasculitis, and can also
be seen in idiopathic
necrotizing and crescentic GN. When assayed by indirect
immunofluorescence, anti-PR3
ANCA produces a cytoplasmic pattern of staining, whereas anti-MPO
produce a perinuclear
pattern, which is largely an artifact of fixation. The question of
falsely positive ANCA
tests is a vexing one, as renal involvement with a positive ANCA
test, if indicative of
vasculitis, often militates for aggressive treatment with cytotoxic
drugs.
In this paper, the question of the prevalence of falsely positive
ANCA tests (e.g., not
associated with vasculitis) in patients with connective tissue
disease is explored. Stored
serum specimens from a study that was designed to study the course
of undifferentiated
connective tissue disease, but which included substantial numbers
of patients with SLE,
scleroderma, Sjogren syndrome, and the antiphospholipid syndrome.
Random blood donors
served as a negative control group, and fifty-two patients with
Wegener
s granulomatosis, microscopic polyangiitis, or related vasculitis
served as positive
controls. ANCA was assayed by both indirect immunofluorescence and
by two ELISA methods
(a direct and a sandwich technique) specific for anti-MPO or
anti-PR3.
ANCA-C was relatively specific, as it was not present in any of the
patients without
vasculitis but with rheumatoid arthritis, lupus, scleroderma, or
polymyositis. Nor was it
present in patients with Sjogren's syndrome or anti-phospholipid
antibody syndrome. P-
ANCA, however, was not nearly as specific, as it occurred
frequently (31%) in patients
with SLE. Atypical ANCA fluorescence, which could not be typed
specifically as
cytoplasmic or perinuclear, was present in 10-20% of various
connective tissue disorders
excluding SLE, and in 39% of SLE patients! Almost none of the
patients positive for P-
ANCA by indirect immunofluorescence were positive for anti-MPO
antibodies by ELISA.
Comment: This is an elegantly done study. The patient
sample size is large, a wide
spectrum of connective tissue diseases are represented, and
follow-up of the patients was
long to make sure that they did not develop signs or symptoms of
vasculitis over a period
as long as 5 years. Furthermore, all samples were assayed in a
blinded fashion. The
clinical message from this study is, that indirect
immunofluorescence tests for ANCA
should not be used to diagnose nor treat patients with vasculitis,
but that more specific
anti-PR3 and anti-MPO ELISA tests should be employed.
(John T. Daugirdas, M.D., University of Illinois at
Chicago)
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