title: Distribution and components of interstitial inflammation and fibrosis in IgG4-related kidney disease: analysis of autopsy specimens.
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.
authors.affiliation: 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.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hara
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa 920-8641, Japan. Electronic address: sk33166@gmail.com.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawano
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa 920-8641, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Mizushima
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.affiliation: Department of Internal Medicine, Nagaoka Chuo General Hospital, Nagaoka 940-8653, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Takata
authors.affiliation: Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka 940-2108, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Saeki
authors.affiliation: Nephrology Center, Toranomon Hospital, Kajigaya 213-8587, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ubara
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Kidney and Vascular Pathology, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Nagata
mesh_terms: D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D003094:Collagen / Q000032:analysis; D005353:Fibronectins / Q000032:analysis; D005355:Fibrosis; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000737:chemistry / Q000473:pathology; D009395:Nephritis, Interstitial / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D005353:Fibronectins; D007074:Immunoglobulin G; D003094:Collagen
keywords: Bird's-eye pattern fibrosis; IgG4-related disease; IgG4-related kidney disease; Interstitial fibrosis; Storiform fibrosis