Complement activation associated with ADAMTS13 deficiency may contribute to the characteristic glomerular manifestations in Upshaw-Schulman syndrome

Hiroe Itami, Shigeo Hara, Masanori Matsumoto, Shin Imamura, Rie Kanai, Kei Nishiyama, masataka ishimura, Shoichi Ohga, Makiko Yoshida, Ryojiro Tanaka, Yoshiyuki Ogawa, Yujiro Asada, Yoko Sekita-Hatakeyama, Kinta Hatakeyama, Chiho Ohbayashi

研究成果: ジャーナルへの寄稿記事

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Introduction: Upshaw-Schulman syndrome (USS) is a congenital form of thrombotic thrombocytopenic purpura (TTP) associated with loss-of-function mutations in the ADAMTS13 gene, possibly leading to aberrant complement activation and vascular injury. However, USS is extremely rare, and there have been no systematic studies correlating histopathological severity with local ADAMTS13 expression and complement activation. Materials and methods: Here, we compared histopathological features, ADAMTS13 immunoreactivity, and immunoreactivity of complement proteins C4d and C5b-9 among renal biopsy tissues from five USS cases, ten acquired TTP cases, and eleven controls. Results: Pathological analysis revealed chronic glomerular sclerotic changes in the majority of USS cases (4 of 5), with minor glomerular pathology in the remaining case. In two of these four severe cases, more than half of the glomerular segmental sclerosis area was localized in the perihilar region. The average number of ADAMTS13-positive cells per glomerulus was significantly lower in USS cases than controls (p < 0.05). Conversely, C4d staining was significantly more prevalent in the glomerular capillary walls of USS cases than controls (p < 0.05), while C5b-9 staining did not differ significantly among groups. Conclusions: These findings suggest that the severity of glomerular injury in USS is associated with deficient ADAMTS13 expression and local complement activation, particularly in vascular regions with higher endothelial shear stress. We suggest that C4d immunostaining provides evidence for complement-mediated glomerular damage in USS.

元の言語英語
ページ(範囲)148-155
ページ数8
ジャーナルThrombosis Research
170
DOI
出版物ステータス出版済み - 10 1 2018

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Thrombotic Thrombocytopenic Purpura
Complement Activation
Complement Membrane Attack Complex
Complement C5b
Staining and Labeling
Vascular System Injuries
Sclerosis
Blood Vessels
Complement System Proteins
Pathology
Kidney
Biopsy
Mutation

All Science Journal Classification (ASJC) codes

  • Hematology

これを引用

Complement activation associated with ADAMTS13 deficiency may contribute to the characteristic glomerular manifestations in Upshaw-Schulman syndrome. / Itami, Hiroe; Hara, Shigeo; Matsumoto, Masanori; Imamura, Shin; Kanai, Rie; Nishiyama, Kei; ishimura, masataka; Ohga, Shoichi; Yoshida, Makiko; Tanaka, Ryojiro; Ogawa, Yoshiyuki; Asada, Yujiro; Sekita-Hatakeyama, Yoko; Hatakeyama, Kinta; Ohbayashi, Chiho.

:: Thrombosis Research, 巻 170, 01.10.2018, p. 148-155.

研究成果: ジャーナルへの寄稿記事

Itami, H, Hara, S, Matsumoto, M, Imamura, S, Kanai, R, Nishiyama, K, ishimura, M, Ohga, S, Yoshida, M, Tanaka, R, Ogawa, Y, Asada, Y, Sekita-Hatakeyama, Y, Hatakeyama, K & Ohbayashi, C 2018, 'Complement activation associated with ADAMTS13 deficiency may contribute to the characteristic glomerular manifestations in Upshaw-Schulman syndrome', Thrombosis Research, 巻. 170, pp. 148-155. https://doi.org/10.1016/j.thromres.2018.08.020
Itami, Hiroe ; Hara, Shigeo ; Matsumoto, Masanori ; Imamura, Shin ; Kanai, Rie ; Nishiyama, Kei ; ishimura, masataka ; Ohga, Shoichi ; Yoshida, Makiko ; Tanaka, Ryojiro ; Ogawa, Yoshiyuki ; Asada, Yujiro ; Sekita-Hatakeyama, Yoko ; Hatakeyama, Kinta ; Ohbayashi, Chiho. / Complement activation associated with ADAMTS13 deficiency may contribute to the characteristic glomerular manifestations in Upshaw-Schulman syndrome. :: Thrombosis Research. 2018 ; 巻 170. pp. 148-155.
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abstract = "Introduction: Upshaw-Schulman syndrome (USS) is a congenital form of thrombotic thrombocytopenic purpura (TTP) associated with loss-of-function mutations in the ADAMTS13 gene, possibly leading to aberrant complement activation and vascular injury. However, USS is extremely rare, and there have been no systematic studies correlating histopathological severity with local ADAMTS13 expression and complement activation. Materials and methods: Here, we compared histopathological features, ADAMTS13 immunoreactivity, and immunoreactivity of complement proteins C4d and C5b-9 among renal biopsy tissues from five USS cases, ten acquired TTP cases, and eleven controls. Results: Pathological analysis revealed chronic glomerular sclerotic changes in the majority of USS cases (4 of 5), with minor glomerular pathology in the remaining case. In two of these four severe cases, more than half of the glomerular segmental sclerosis area was localized in the perihilar region. The average number of ADAMTS13-positive cells per glomerulus was significantly lower in USS cases than controls (p < 0.05). Conversely, C4d staining was significantly more prevalent in the glomerular capillary walls of USS cases than controls (p < 0.05), while C5b-9 staining did not differ significantly among groups. Conclusions: These findings suggest that the severity of glomerular injury in USS is associated with deficient ADAMTS13 expression and local complement activation, particularly in vascular regions with higher endothelial shear stress. We suggest that C4d immunostaining provides evidence for complement-mediated glomerular damage in USS.",
author = "Hiroe Itami and Shigeo Hara and Masanori Matsumoto and Shin Imamura and Rie Kanai and Kei Nishiyama and masataka ishimura and Shoichi Ohga and Makiko Yoshida and Ryojiro Tanaka and Yoshiyuki Ogawa and Yujiro Asada and Yoko Sekita-Hatakeyama and Kinta Hatakeyama and Chiho Ohbayashi",
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T1 - Complement activation associated with ADAMTS13 deficiency may contribute to the characteristic glomerular manifestations in Upshaw-Schulman syndrome

AU - Itami, Hiroe

AU - Hara, Shigeo

AU - Matsumoto, Masanori

AU - Imamura, Shin

AU - Kanai, Rie

AU - Nishiyama, Kei

AU - ishimura, masataka

AU - Ohga, Shoichi

AU - Yoshida, Makiko

AU - Tanaka, Ryojiro

AU - Ogawa, Yoshiyuki

AU - Asada, Yujiro

AU - Sekita-Hatakeyama, Yoko

AU - Hatakeyama, Kinta

AU - Ohbayashi, Chiho

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Introduction: Upshaw-Schulman syndrome (USS) is a congenital form of thrombotic thrombocytopenic purpura (TTP) associated with loss-of-function mutations in the ADAMTS13 gene, possibly leading to aberrant complement activation and vascular injury. However, USS is extremely rare, and there have been no systematic studies correlating histopathological severity with local ADAMTS13 expression and complement activation. Materials and methods: Here, we compared histopathological features, ADAMTS13 immunoreactivity, and immunoreactivity of complement proteins C4d and C5b-9 among renal biopsy tissues from five USS cases, ten acquired TTP cases, and eleven controls. Results: Pathological analysis revealed chronic glomerular sclerotic changes in the majority of USS cases (4 of 5), with minor glomerular pathology in the remaining case. In two of these four severe cases, more than half of the glomerular segmental sclerosis area was localized in the perihilar region. The average number of ADAMTS13-positive cells per glomerulus was significantly lower in USS cases than controls (p < 0.05). Conversely, C4d staining was significantly more prevalent in the glomerular capillary walls of USS cases than controls (p < 0.05), while C5b-9 staining did not differ significantly among groups. Conclusions: These findings suggest that the severity of glomerular injury in USS is associated with deficient ADAMTS13 expression and local complement activation, particularly in vascular regions with higher endothelial shear stress. We suggest that C4d immunostaining provides evidence for complement-mediated glomerular damage in USS.

AB - Introduction: Upshaw-Schulman syndrome (USS) is a congenital form of thrombotic thrombocytopenic purpura (TTP) associated with loss-of-function mutations in the ADAMTS13 gene, possibly leading to aberrant complement activation and vascular injury. However, USS is extremely rare, and there have been no systematic studies correlating histopathological severity with local ADAMTS13 expression and complement activation. Materials and methods: Here, we compared histopathological features, ADAMTS13 immunoreactivity, and immunoreactivity of complement proteins C4d and C5b-9 among renal biopsy tissues from five USS cases, ten acquired TTP cases, and eleven controls. Results: Pathological analysis revealed chronic glomerular sclerotic changes in the majority of USS cases (4 of 5), with minor glomerular pathology in the remaining case. In two of these four severe cases, more than half of the glomerular segmental sclerosis area was localized in the perihilar region. The average number of ADAMTS13-positive cells per glomerulus was significantly lower in USS cases than controls (p < 0.05). Conversely, C4d staining was significantly more prevalent in the glomerular capillary walls of USS cases than controls (p < 0.05), while C5b-9 staining did not differ significantly among groups. Conclusions: These findings suggest that the severity of glomerular injury in USS is associated with deficient ADAMTS13 expression and local complement activation, particularly in vascular regions with higher endothelial shear stress. We suggest that C4d immunostaining provides evidence for complement-mediated glomerular damage in USS.

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U2 - 10.1016/j.thromres.2018.08.020

DO - 10.1016/j.thromres.2018.08.020

M3 - Article

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VL - 170

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EP - 155

JO - Thrombosis Research

JF - Thrombosis Research

SN - 0049-3848

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