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Hum Pathol. 2016 Sep;55:164-73. doi: 10.1016/j.humpath.2016.05.010. Epub 2016 May 28.

Distribution and components of interstitial inflammation and fibrosis in IgG4-related kidney disease: analysis of autopsy specimens.

Author information

1
Department of Kidney and Vascular Pathology, University of Tsukuba, Tsukuba 305-8575, Japan; Division of Rheumatology, Department of Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa 920-8641, Japan.
2
Division of Rheumatology, Department of Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa 920-8641, Japan. Electronic address: sk33166@gmail.com.
3
Division of Rheumatology, Department of Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa 920-8641, Japan.
4
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
5
Department of Internal Medicine, Nagaoka Chuo General Hospital, Nagaoka 940-8653, Japan.
6
Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka 940-2108, Japan.
7
Nephrology Center, Toranomon Hospital, Kajigaya 213-8587, Japan.
8
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
9
Department of Kidney and Vascular Pathology, University of Tsukuba, Tsukuba 305-8575, Japan.

Abstract

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.

KEYWORDS:

Bird's-eye pattern fibrosis; IgG4-related disease; IgG4-related kidney disease; Interstitial fibrosis; Storiform fibrosis

PMID:
27246178
DOI:
10.1016/j.humpath.2016.05.010
[Indexed for MEDLINE]
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