Abstract
Introduction: IgA nephropathy (IgAN) with serum antineutrophil cytoplasmic autoantibody (ANCA) positivity is uncommon. This study analyzed the clinicopathologic features and prognosis of IgAN patients with serum ANCA positivity. Methods: 2,864 IgAN patients were tested for ANCA by the indirect immunofluorescence assay and chemiluminescence immunoassay. Patients with serum ANCA positivity (n = 85) were identified, and their clinical, pathological, and prognostic characteristics were analyzed. They were compared with ANCA-negative IgAN patients (n = 170) and ANCA-associated systemic vasculitis (AAV) with renal involvement patients (n = 85) selected randomly. Results: 2.97% (85/2,864) of IgAN were ANCA positive, and 4 patients were diagnosed as having crescentic IgAN with ANCA positivity. The clinicopathological characteristics of ANCA-positive IgAN patients were comparable to ANCA-negative IgAN patients, but they had higher antinuclear antibody (ANA)-positive rates, lower levels of renal interstitial inflammation, and fewer immune depositions than ANCA-negative IgAN patients. Compared with AAV patients, ANCA-positive IgAN patients were younger and had fewer extrarenal manifestations, milder renal damage, and more immune complex depositions. The renal outcomes were similar between IgAN patients with and without ANCA positivity. Multivariate Cox analysis revealed that in IgAN patients with ANCA positivity, male, ANA positivity, higher serum creatinine and proteinuria, and more severe renal tubular atrophy/interstitial fibrosis were risk factors for adverse renal outcomes. Conclusion: The clinical, pathological features and prognosis of ANCA-positive IgAN patients were similar to those of ANCA-negative IgAN patients except for higher ANA-positive rate, milder renal inflammation, and fewer immune depositions. ANA positivity was an independent risk factor for adverse renal outcomes in ANCA-positive IgAN patients.
References
1.
Lai
KN
, Tang
SC
, Schena
FP
, Novak
J
, Tomino
Y
, Fogo
AB
. IgA nephropathy
. Nat Rev Dis Primers
. 2016
;2
:16001
.2.
Kitching
AR
, Anders
HJ
, Basu
N
, Brouwer
E
, Gordon
J
, Jayne
DR
. ANCA-associated vasculitis
. Nat Rev Dis Primers
. 2020
;6
(1
):71
.3.
Shimizu
M
, Wada
T
, Sakai
N
, Izumiya
Y
, Furuichi
K
, Misaki
T
. Clinicopathological features of antineutrophil cytoplasmic antibodies-associated vasculitis in Japanese Patients with IgA nephropathy
. Clin Exp Nephrol
. 2000
;4
(3
):251
–6
.4.
Uchiyama
M
, Akahoshi
T
, Matsui
T
, Watabe
H
, Koredo
K
, Tanaka
S
. Crescentic glomerulonephritis with antimyeloperoxidase antibodies developing during the course of IgA nephropathy in a patient with rheumatoid arthritis
. Mod Rheumatol
. 2001
;11
(1
):76
–9
.5.
Lui
SL
, Chan
KW
, Yip
PS
, Chan
TM
, Lai
KN
, Lo
WK
. Simultaneous occurrence of diabetic glomerulosclerosis, IgA nephropathy, crescentic glomerulonephritis, and myeloperoxidase-antineutrophil cytoplasmic antibody seropositivity in a Chinese patient
. Am J Kidney Dis
. 2002
40
4
E14
.6.
Amir
AR
, Sheikh
SS
. ANCA-associated crescentic IgA glomerulonephritis in pregnancy
. J Nephrol
. 2002
;15
(6
):716
–9
.7.
Rocco
VK
, Horn
RG
, Fogo
AB
. Quiz page. IgA nephropathy and superimposed pauci-immune necrotizing crescentic glomerulonephritis, the latter clinically typical of Wegener's granulomatosis
. Am J Kidney Dis
. 2002
40
6
xli
.8.
Winters
MJ
, Hurley
RM
, Lirenman
DS
. ANCA-positive glomerulonephritis and IgA nephropathy in a patient on propylthiouracil
. Pediatr Nephrol
. 2002
;17
(4
):257
–60
.9.
Ogawa
N
, Yano
S
, Yamane
Y
, Nishiki
M
, Yamaguchi
T
, Tsukamoto
T
. MPO-ANCA-positive IgA nephropathy successfully treated with tonsillectomy
. Clin Exp Nephrol
. 2007
;11
(4
):326
–31
.10.
Ku
E
, Ananthapanyasut
W
, Campese
VM
. IgA nephropathy in a patient with ulcerative colitis, Graves’ disease and positive myeloperoxidase ANCA
. Clin Nephrol
. 2012
;77
(2
):146
–50
.11.
Ozkok
A
, Makbule Sirin
B
, Celal Elcioglu
O
, Bakan
A
, Riza Odabas
A
. Crescentic glomerulonephritis due to IgA nephropathy or propylthiouracil- induced Mpo-Anca positive vasculitis
. Ren Fail
. 2013
;35
(6
):930
.12.
Barcelos
FL
, Fontes
TM
. Case report: IgA nephropathy ANCA positive with favorable outcome
. J Bras Nefrol
. 2015
;37
(3
):414
–7
.13.
Kucuk
A
, Solak
Y
, Gaipov
A
, Bagcaci
S
, Esen
H
, Turk
S
. Co-existing proteinase 3-antineutrophil cytoplasmic antibody-associated vasculitis with immunoglobulin A nephropathy
. Korean J Intern Med
. 2016
;31
(1
):194
–6
.14.
Yasukawa
M
, Kitagawa
S
, Togashi
R
, Asakawa
S
, Nagura
M
, Arai
S
. A patient with MPO-ANCA-positive IgA nephropathy diagnosed with the clinical onset of macrohematuria
. Intern Med
. 2019
;58
(14
):2051
–6
.15.
Rao
N
, Bendall
A
, Lanteri
M
. ANCA vasculitis and IgA nephropathy linked to silica exposure
. Occup Med
. 2020
;70
(6
):445
–8
.16.
Krasselt
M
, Halbritter
J
, Amann
K
, Baerwald
C
, Seifert
O
. ANCA-positive IgA nephropathy in a patient with ANA-positive long-standing rheumatoid arthritis and type 1 diabetes
. Clin Exp Rheumatol
. 2020
38 Suppl 14
2
241
2
.17.
Bantis
C
, Stangou
M
, Schlaugat
C
, Alexopoulos
E
, Pantzaki
A
, Memmos
D
. Is presence of ANCA in crescentic IgA nephropathy a coincidence or novel clinical entity? A case series
. Am J Kidney Dis
. 2010
;55
(2
):259
–68
.18.
Huang
X
, Wang
Y
, Xie
L
, Zhang
Y
, Tang
S
, Yin
S
. IgA nephropathy with anti-neutrophil cytoplasmic antibody seropositivity
. Clin Nephrol
. 2015
;84
(3
):156
–64
.19.
Ștefan
G
, Terinte-Balcan
G
, Stancu
S
, Zugravu
A
, Gherghiceanu
M
, Mircescu
G
. IgA nephropathy with serum ANCA positivity: case series and literature review
. Rheumatol Int
. 2021
;41
(7
):1347
–55
.20.
Yang
YZ
, Shi
SF
, Chen
YQ
, Chen
M
, Yang
YH
, Xie
XF
. Clinical features of IgA nephropathy with serum ANCA positivity: a retrospective case-control study
. Clin Kidney J
. 2015
;8
(5
):482
–8
.21.
Xie
L
, He
J
, Liu
X
, Tang
S
, Wang
W
, Li
F
. Clinical value of systemic symptoms in IgA nephropathy with ANCA positivity
. Clin Rheumatol
. 2018
;37
(7
):1953
–61
.22.
Jennette
JC
, Falk
RJ
, Bacon
PA
, Basu
N
, Cid
MC
, Ferrario
F
. 2012 revised international Chapel Hill Consensus conference nomenclature of vasculitides
. Arthritis Rheum
. 2013 Jan
65
1
1
11
.23.
Mukhtyar
C
, Lee
R
, Brown
D
, Carruthers
D
, Dasgupta
B
, Dubey
S
. Modifification and validation of the Birmingham vasculitis activity score (version 3)
. Ann Rheum Dis
. 2009
;68
(12
):1827
–32
.24.
Levey
AS
, Stevens
LA
, Schmid
CH
, Zhang
YL
, Castro
AF
3rd, Feldman
HI
. A new equation to estimate glomerular filtration rate
. Ann Intern Med
. 2009
;150
(9
):604
–12
.25.
Trimarchi
H
, Barratt
J
, Cattran
DC
, Cook
HT
, Coppo
R
, Haas
M
. Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group
. Kidney Int
. 2017
;91
(5
):1014
–21
.26.
Rauen
T
, Eitner
F
, Fitzner
C
, Sommerer
C
, Zeier
M
, Otte
B
. Intensive supportive care plus immunosuppression in IgA nephropathy
. N Engl J Med
. 2015 Dec 3
373
23
2225
36
.27.
Hou
FF
, Xie
D
, Wang
J
, Xu
X
, Yang
X
, Ai
J
. Effectiveness of mycophenolate mofetil among patients with progressive IgA nephropathy: a randomized clinical trial
. JAMA Netw Open
. 2023 Feb 1
6
2
e2254054
.28.
Roth
AJ
, Ooi
JD
, Hess
JJ
, van Timmeren
MM
, Berg
EA
, Poulton
CE
. Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis
. J Clin Invest
. 2013
;123
(4
):1773
–83
.29.
Land
J
, Rutgers
A
, Kallenberg
CG
. Anti-neutrophil cytoplasmic autoantibody pathogenicity revisited: pathogenic versus non-pathogenic anti-neutrophil cytoplasmic autoantibody
. Nephrol Dial Transplant
. 2014
;29
(4
):739
–45
.30.
Cui
Z
, Zhao
MH
, Segelmark
M
, Hellmark
T
. Natural autoantibodies to myeloperoxidase, proteinase 3, and the glomerular basement membrane are present in normal individuals
. Kidney Int
. 2010
;78
(6
):590
–7
.31.
Brons
RH
, Kallenberg
CG
, Tervaert
JW
. Are antineutrophil cytoplasmic antibody-associated vasculitides pauci-immune
. Rheum Dis Clin North Am
. 2001
;27
(4
):833
–48
.32.
Cream
JJ
, Bryceson
AD
, Ryder
G
. Disappearance of immunoglobulin and complement from the Arthus reaction and its relevance to studies of vasculitis in man
. Br J Dermatol
. 1971
;84
(2
):106
–9
.33.
Charles
GC
, WilliamOW
, Frank
JD
. The role of polymorphonuclear leukocytes in the initiation and cessation of the Arthus vasculitis
. J Exp Med
. 1959
;110
(3
):481
–94
.34.
Wallace
ZS
, Stone
JH
. Personalized medicine in ANCA-associated vasculitis ANCA specificity as the guide
. Front Immunol
. 2019
;10
:2855
.35.
Pearce
FA
, Craven
A
, Merkel
PA
, Luqmani
RA
, Watts
RA
. Global ethnic and geographic differences in the clinical presentations of anti-neutrophil cytoplasm antibody-associated vasculitis
. Rheumatology
. 2017
;56
(11
):1962
–9
.36.
Hong
Y
, Shi
P
, Liu
X
, Yang
L
, Li
K
, Xu
F
. Distinction between MPO-ANCA and PR3-ANCA-associated glomerulonephritis in Chinese patients: a retrospective single-center study
. Clin Rheumatol
. 2019
;38
(6
):1665
–73
.37.
Wu
T
, Shen
C
, Zhong
Y
, Ooi
JD
, Zhou
YO
, Chen
JB
. Differences between myeloperoxidase- antineutrophil cytoplasmic autoantibody (ANCA) and proteinase 3-ANCA associated vasculitis: a retrospective study from a single center in China
. Exp Ther Med
. 2021
;21
(6
):561
.38.
Huang
PP
, Shu
DH
, Su
Z
, Luo
SN
, Xu
FF
, Lin
F
. Association between lifestyle, gender and risk for developing end-stage renal failure in IgA nephropathy: a case-control study within 10 years
. Ren Fail
. 2019 Nov
41
1
914
20
.39.
Maixnerova
D
, Reily
C
, Bian
Q
, Neprasova
M
, Novak
J
, Tesar
V
. Markers for the progression of IgA nephropathy
. J Nephrol
. 2016 Aug
29
4
535
41
.40.
Savige
JA
, Chang
L
, Wilson
D
, Buchanan
RR
. Autoantibodies and target antigens in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides
. Rheumatol Int
. 1996
;16
(3
):109
–14
.41.
Nagy
J
, Goshen
E
, Livne
A
, Sarov
I
, Shoenfeld
Y
. Antinuclear antibodies in IgA nephropathy, as well as mesangiocapillary and membranous glomerulonephritis
. Orv Hetil
. 1991 Mar 24
132
12
623
8
.42.
Goshen
E
, Livne
A
, Nagy
J
, Sarov
I
, Shoenfeld
Y
. Antinuclear autoantibodies in sera of patients with IgA nephropathy
. Nephron
. 1990
;55
(1
):33
–6
.43.
Zhao
X
, Wen
Q
, Qiu
Y
, Huang
F
. Clinical and pathological characteristics of ANA/anti-dsDNA positive patients with antineutrophil cytoplasmic autoantibody-associated vasculitis
. Rheumatol Int
. 2021
;41
(2
):455
–62
.44.
Vanga
A
, Rana
AZ
, Kowalewska
J
, Rust
H
. Corrigendum to “pericardial tamponade: an uncommon clinical presentation in cANCA related vasculitis and glomerulonephritis in association with very high titres of ANA”
. Case Rep Nephrol
. 2019 Aug 22
2019
6703652
.45.
Lenert
P
, Icardi
M
, Dahmoush
L
. ANA (+) ANCA (+) systemic vasculitis associated with the use of minocycline: case-based review
. Clin Rheumatol
. 2013
;32
(7
):1099
–106
.46.
Hacking
S
, Uppal
NN
, Khan
N
, Ionescu
M
, Bijol
V
. Systemic p-ANCA vasculitis with fatal outcome, arising in the setting of methimazole use
. Clin Nephrol Case Stud
. 2019
;7
:23
–6
.
