ABSTRACT
Objective:
To investigate the
role of the
NOD-like receptor thermal
protein domain associated
protein 3(NLRP3)
inflammasome and its
downstream interleukin(IL)-1β,
IL-6, and
IL-18 in the pathogenesis of
antineutrophil cytoplasmic antibody-associated
vasculitis(AAV) in
children.
Methods:
A
retrospective study was conducted.Specifically, the
localization and expression of the NLRP3
inflammasome in renal
tissues of 22
children who were diagnosed with primary AAV and underwent renal
biopsy in the Department of Pediatric
Nephrology and
Rheumatology, the First Affiliated
Hospital of
Sun Yat-Sen
University from September 2003 to September 2020 were detected by the immunohistochemical
method.The
IL-1β,
IL-6 and
IL-18 levels in
serum and
urine were measured by
enzyme-linked immunosorbent assay.The measurement data conforming to
normal distribution were compared by the t test between two groups and by the single factor
ANOVA test among multiple groups.The measurement data that did not conform to
normal distribution were compared by the Wilcoxon signed rank sum test.
Classification variables were examined by the χ2 test. Pearson correlation coefficient or
Spearman rank correlation coefficient were used to analyze the correlation among variables.
Results:
NLRP3 was widely expressed in the tubulointerstitium, and the expression level in the active group was higher than that in the
control group, the semi-quantitative scores of NLRP3 in the renal tubule and glomeruli in the active group were higher than those in the
control group ( F=0.859, 8.320, all P<0.05). In the active group, the semi-quantitative score of NLRP3 in the renal tubule was higher than that in the glomeruli( F=3.517, P<0.05). The semi-quantitative score of NLRP3 in the renal tubule was positively correlated with the pediatric
vasculitis activity score at renal
biopsy ( r=0.471, P=0.027)and negatively correlated with the estimated
glomerular filtration rate at renal
biopsy ( r=-0.548, P=0.008)in the active group.The
serum IL-1β,
serum IL-18 and urinary
IL-6 levels in the active group were higher than those in the remission group and the
control group ( F=16.449, 16.449, 0.637, 29.891, 27.612, 7.464, all P<0.05). The
serum IL-18 level in the remission group was higher than that in the
control group( F=18.671, P<0.05). In the active group, a positive correlation was found between the
serum IL-1β level and the semi-quantitative score of NLRP3 in the renal tubule( r=0.805, P=0.002), between the
serum IL-6 level and the
C-reactive protein level at renal
biopsy ( r=0.728, P=0.017), and between the urinary
IL-6 level and the crescent proportion at renal
biopsy ( r=0.677, P=0.032). The
serum IL-18 level in the active group was positively correlated with the semi-quantitative score of NLRP3 in the renal tubule, pediatric
vasculitis activity score and glomerular
sclerosis proportion at renal
biopsy, and negatively correlated with the estimated
glomerular filtration rate at renal
biopsy ( r=0.644, 0.612, 0.695, -0.577, all P<0.05). The urinary
IL-18 level was positively correlated with the
complement C 4 level at renal
biopsy ( r=0.855, P<0.05).
Conclusions:
The NLRP3
inflammasome and its
downstream IL-1β,
IL-6, and
IL-18 may be involved in the pathogenesis and progression of AAV, and can be used as one of the reference
indicators for
disease activity assessment.