TY - JOUR
T1 - Distribution and components of interstitial inflammation and fibrosis in IgG4-related kidney disease
T2 - analysis of autopsy specimens
AU - Hara, Satoshi
AU - Kawano, Mitsuhiro
AU - Mizushima, Ichiro
AU - Harada, Kenichi
AU - Takata, Takuma
AU - Saeki, Takako
AU - Ubara, Yoshifumi
AU - Sato, Yasuharu
AU - Nagata, Michio
N1 - Funding Information:
Funding/Support: This work was supported by Health and Labour Sciences Research Grants for the Study of Intractable Diseases from the Ministry of Health, Labour and Welfare, Japan.
Publisher Copyright:
© 2016 The Authors
PY - 2016/9/1
Y1 - 2016/9/1
N2 - IgG4-related kidney disease (IgG4-RKD) occasionally progresses to chronic renal failure and is pathologically characterized by IgG4-positive lymphoplasmacyte-rich tubulointerstitial nephritis with storiform fibrosis (bird's-eye pattern fibrosis). Although radiology reveals a heterogeneous distribution of affected areas in this disease, their true distribution within the whole kidney is still unknown because of difficulty in estimating this from needle biopsy samples. Using 5 autopsy specimens, the present study histologically characterized the distribution and components of interstitial inflammation and fibrosis in IgG4-RKD. Interstitial lymphoplasmacytic infiltration or fibrosis was observed in a variety of anatomical locations such as intracapsular, subcapsular, cortical, perivascular, and perineural regions heterogeneously in a patchy distribution. They tended to be more markedly accumulated around medium- and small-sized vessels. Storiform fibrosis was limited to the cortex. Immunostaining revealed nonfibrillar collagens (collagen IV and VI) and fibronectin predominance in the cortical lesion, including storiform fibrosis. In contrast, fibril-forming collagens (collagen I and III), collagen VI, and fibronectin were the main components in the perivascular lesion. In addition, α-smooth muscle actin–positive myofibroblasts were prominently accumulated in the early lesion and decreased with progression, suggesting that myofibroblasts produce extracellular matrices forming a peculiar fibrosis. In conclusion, perivascular inflammation or fibrosis of medium- and small-sized vessels is a newly identified pathologic feature of IgG4-RKD. Because storiform fibrosis contains mainly nonfibrillar collagens, “interstitial fibrosclerosis” would be a suitable term to reflect this. The relation between the location and components of fibrosis determined in whole kidney samples provides new clues to the pathophysiology underlying IgG4-RKD.
AB - IgG4-related kidney disease (IgG4-RKD) occasionally progresses to chronic renal failure and is pathologically characterized by IgG4-positive lymphoplasmacyte-rich tubulointerstitial nephritis with storiform fibrosis (bird's-eye pattern fibrosis). Although radiology reveals a heterogeneous distribution of affected areas in this disease, their true distribution within the whole kidney is still unknown because of difficulty in estimating this from needle biopsy samples. Using 5 autopsy specimens, the present study histologically characterized the distribution and components of interstitial inflammation and fibrosis in IgG4-RKD. Interstitial lymphoplasmacytic infiltration or fibrosis was observed in a variety of anatomical locations such as intracapsular, subcapsular, cortical, perivascular, and perineural regions heterogeneously in a patchy distribution. They tended to be more markedly accumulated around medium- and small-sized vessels. Storiform fibrosis was limited to the cortex. Immunostaining revealed nonfibrillar collagens (collagen IV and VI) and fibronectin predominance in the cortical lesion, including storiform fibrosis. In contrast, fibril-forming collagens (collagen I and III), collagen VI, and fibronectin were the main components in the perivascular lesion. In addition, α-smooth muscle actin–positive myofibroblasts were prominently accumulated in the early lesion and decreased with progression, suggesting that myofibroblasts produce extracellular matrices forming a peculiar fibrosis. In conclusion, perivascular inflammation or fibrosis of medium- and small-sized vessels is a newly identified pathologic feature of IgG4-RKD. Because storiform fibrosis contains mainly nonfibrillar collagens, “interstitial fibrosclerosis” would be a suitable term to reflect this. The relation between the location and components of fibrosis determined in whole kidney samples provides new clues to the pathophysiology underlying IgG4-RKD.
KW - Bird's-eye pattern fibrosis
KW - IgG4-related disease
KW - IgG4-related kidney disease
KW - Interstitial fibrosis
KW - Storiform fibrosis
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U2 - 10.1016/j.humpath.2016.05.010
DO - 10.1016/j.humpath.2016.05.010
M3 - Article
C2 - 27246178
AN - SCOPUS:84978044140
SN - 0046-8177
VL - 55
SP - 164
EP - 173
JO - Human Pathology
JF - Human Pathology
ER -