Serum IgA/C3 and glomerular C3 staining predict severity of IgA
Yukihiko Kawasaki, Ryo Maeda, Shinichiro Ohara, Kazuhide Suyama and Mitsuaki Hosoya
Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan
Abstract Background: The aim of this study was to determine whether serum immunoglobulin A/complement factor 3 (IgA/
C3) ratio and glomerular C3 staining predict outcome in IgA nephropathy.
Methods: We collected data for 44 IgA nephropathy children treated with multi-drug combination therapy. The
children were retrospectively divided into four groups based on serum IgA/C3 ratio and glomerular C3 staining:
group A, IgA/C3 ratio >2.68 (median) and glomerular C3 staining ≥2.0, n = 9; group B, IgA/C3 ratio >2.68 and
glomerular C3 staining <2.0, n = 7; group C, IgA/C3 ratio <2.68 and glomerular C3 staining ≥2.0, n = 7; and group
D, IgA/C3 ratio <2.68 and glomerular C3 staining <2.0, n = 21. Clinical features; pathology at the ﬁrst and second
renal biopsy and at the latest follow up; and prognosis were analyzed for the four groups.
Results: At the most recent follow up, urinary protein excretion, incidence of hematuria, and serum creatinine in
group A were all higher than in group D. At the second biopsy, crescent absence/presence ratio; mesangial hyper-
cellularity, segmental glomerulosclerosis or adhesion, endocapillary hypercellularity, and tubular atrophy/interstitial
ﬁbrosis as well as crescents and global glomerulosclerosis (MESTCG) score; and clonicity index in group A were
higher than in group D. All patients in group D had normal urine, and the prevalence of persistent nephropathy in
group A was higher than in group D.
Conclusions: Serum IgA/C3 ratio and glomerular C3 staining can predict outcome in IgA nephropathy.
Key words glomerular C3 staining, IgA nephropathy, mizoribine, multi-drug combination therapy, prognosis, serum IgA/C3.
Immunoglobulin A nephropathy (IgAN) is the most common
form of primary glomerulonephritis in the world today. It
was initially considered to be a benign disease with a favor-
able prognosis, but according to more recent long-term
follow-up data, the disease progresses to renal failure in
10–15% of pediatric patients.
It was also recently noted
that the pathogenesis of IgAN may be associated with the
circulation of defective forms of IgA1 or the presence of
in situ immune complexes, and the onset and progression of
inﬂammation are thought to be associated with complement
components, activated macrophages and mesangial cells.
With regard to the prognosis of IgAN, clinical predictors of
poor outcome include renal insufﬁciency, heavier degrees of
proteinuria during the follow-up period, and hypertension,
while pathologic features of poor prognosis include glomeru-
lar sclerosis, interstitial ﬁbrosis and tubular atrophy.
are few useful laboratory markers, however, for predicting
treatment response and outcome of IgAN at diagnosis or
prior to treatment.
With regard to serum IgA level, serum IgA and galac-
tose-deﬁcient (GD) -IgA1 in adult IgAN are higher than in
Ishiguro et al. reported that the serum IgA/com-
plement factor 3 (IgA/C3) ratio in adult IgAN was higher
than in other glomerular disease, and that the serum IgA/C3
ratio appears to increase gradually according to the prognos-
tic grading of this disease.
In contrast, the onset and progression of inﬂammation are
thought to be associated with the activation of the complement
system, including the alternative and lectin pathways. Komatsu
reported that the degree of C3 deposition was associ-
ated with the severity of the pathology. Suzuki et al.
that serum IgA was signiﬁcantly higher, while C3 was lower
in severe IgAN compared with non-IgAN. Thus, we specu-
lated that we could more exactly predict the outcome of IgAN
using a combination of serum IgA/C3 ratio and glomerular C3
staining. In addition, there have been no reports on the rela-
tionship between IgA/C3 ratio and glomerular C3 staining in
terms of the treatment response and prognosis in pediatric
We therefore evaluated the relationship between serum
IgA/C3 ratio, glomerular C3 staining and the clinical and labo-
ratory ﬁndings, as well as the pathology and prognosis, in
children with severe IgAN, who were divided into four groups
according to serum IgA/C3 ratio and degree of glomerular C3
Correspondence: Yukihiko Kawasaki, MD PhD, Department of
Pediatrics, Fukushima Medical University School of Medicine, 1
Hikariga-oka, Fukushima City, Fukushima 960-1295, Japan.
Received 27 July 2017; revised 17 October 2017; accepted 22
© 2017 Japan Pediatric Society
Pediatrics International (2018) 60, 162–167 doi: 10.1111/ped.13461