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2016 ; 11
(4
): 568-75
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Autoantibodies against Linear Epitopes of Myeloperoxidase in Anti-Glomerular
Basement Membrane Disease
#MMPMID26813562
Li JN
; Cui Z
; Wang J
; Hu SY
; Jia XY
; Guan Z
; Chen M
; Xie C
; Zhao MH
Clin J Am Soc Nephrol
2016[Apr]; 11
(4
): 568-75
PMID26813562
show ga
BACKGROUND AND OBJECTIVES: Approximately 20%-30% of patients with anti-glomerular
basement membrane disease present coexisting anti-myeloperoxidase (MPO)
autoantibodies. We previously showed the recognition of a linear fragment of the
MPO heavy chain N-terminus ((1)H, MPO279-409) in plasma from most double-positive
patients. Herein, we investigated the frequency of autoantibodies against
overlapping (1)H-derived linear peptides in plasma from patients with
anti-glomerular basement membrane disease. DESIGN, SETTING, PARTICIPANTS, &
MEASUREMENTS: We synthesized 13 overlapping linear peptides ((1)H-1 to (1)H-13)
covering MPO279-409. We retrospectively collected plasma samples from 67 patients
with anti-glomerular basement membrane disease from 1996 to 2012, and we screened
them for IgG autoantibodies by ELISA using intact human MPO and the overlapping
peptides as antigens, and we further investigated the clinical significance.
Autoantibody binding to the linear MPO structure was confirmed by Western
blotting. RESULTS: We followed up the 67 patients until 2015, with a median
follow-up time of 10.0 (2.3-36.0) months, and 56 ESRD events occurred among the
67 patients with follow-up data. Plasma from 23.9% (16) of the patients
recognized intact human MPO, whereas 62.7% (42) plasma samples recognized
MPO279-409 linear peptides. Of the 13 linear peptides, (1)H-4 (44.8%, 30
patients) and (1)H-12 (40.3%, 27 patients) exhibited the highest recognition
frequencies. Patients with autoantibodies against (1)H-11 or (1)H-12 (MPO371-400)
were older (46.1±18.8 versus 34.1±16.6 years; P<0.01), had higher serum
creatinine upon diagnosis (median 7.8 mg/dl, interquartile range 4.9-12.6 mg/dl
versus median 5.4 mg/dl, interquartile range 2.4-7.3 mg/dl; P=0.02), and had a
higher probability of progressing to ESRD; however, multivariate Cox regression
analysis showed that (1)H-11 or 12 reaction was not an independent risk factor
for renal failure (hazard ratio, 1.2; 95% confidence interval, 0.8 to 2.8;
P=0.19). CONCLUSIONS: Autoantibodies against linear peptides of MPO can be
detected in the majority of patients with anti-glomerular basement membrane
disease, and several are associated with disease severity. The potential common
pathogenic mechanism between anti-glomerular basement membrane antibodies and
anti-MPO autoantibodies in anti-glomerular basement membrane disease requires
further investigation.