Vascular endothelial growth factor (VEGF)-A and VEGF-A165b are associated with time to remission of granulomatosis with polyangiitis in a nationwide Japanese prospective cohort study

Ryosuke Kikuchi; Naotake Tsuboi; Ken-Ei Sada; Masahiro Nakatochi; Yuki Yokoe; Atsuo Suzuki; Shoichi Maruyama; Toyoaki Murohara; Tadashi Matsushita; Research Committee of Intractable Vasculitis Syndrome and Research Committee of Intractable Renal Disease of the Ministry of Health, Labour and Welfare of Japan; Koichi Amano; Tatsuya Atsumi; Yoshinari Takasaki; Satoshi Ito; Hitoshi Hasegawa; Hiroaki Dobashi; Takafumi Ito; Hirofumi Makino; Seiichi Matsuo

doi:10.1177/0004563220968371

Vascular endothelial growth factor (VEGF)-A and VEGF-A₁₆₅b are associated with time to remission of granulomatosis with polyangiitis in a nationwide Japanese prospective cohort study

Ann Clin Biochem. 2021 Mar;58(2):86-94. doi: 10.1177/0004563220968371. Epub 2020 Nov 22.

Authors

Ryosuke Kikuchi¹, Naotake Tsuboi², Ken-Ei Sada^{3

4}, Masahiro Nakatochi⁵, Yuki Yokoe⁶, Atsuo Suzuki⁷, Shoichi Maruyama⁶, Toyoaki Murohara⁷, Tadashi Matsushita^{8

9}; Research Committee of Intractable Vasculitis Syndrome and Research Committee of Intractable Renal Disease of the Ministry of Health, Labour and Welfare of Japan; Koichi Amano¹⁰, Tatsuya Atsumi¹¹, Yoshinari Takasaki¹², Satoshi Ito¹³, Hitoshi Hasegawa¹⁴, Hiroaki Dobashi¹⁵, Takafumi Ito¹⁶, Hirofumi Makino¹⁷, Seiichi Matsuo¹⁸

Affiliations

¹ Department of Medical Technique, Nagoya University Hospital, Nagoya, Japan.
² Department of Nephrology, School of Medicine, Fujita Health University, Nagoya, Japan.
³ Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁴ Department of Clinical Epidemiology, Kochi Medical School, Kochi University, Nankoku, Japan.
⁵ Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁶ Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁷ Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁸ Department of Clinical Laboratory, Nagoya University Hospital, Nagoya, Japan.
⁹ Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan.
¹⁰ Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
¹¹ Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Hokkaido University, Hokkaido, Japan.
¹² Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
¹³ Department of Rheumatology, Niigata Rheumatic Center, Niigata, Japan.
¹⁴ Department of Hematology, Clinical Immunology, and Infectious Diseases, Ehime University Graduate School of Medicine, Ehime, Japan.
¹⁵ Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
¹⁶ Division of Nephrology, Shimane University, Faculty of Medicine, Shimane, Japan.
¹⁷ Okayama University, Okayama, Japan.
¹⁸ Nagoya University, Nagoya, Japan.

PMID: 33081494
DOI: 10.1177/0004563220968371

Abstract

Background: Effective prognostic markers are needed for antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study evaluated the clinical associations of serum vascular endothelial growth factor-A (sVEGF-A) and sVEGF-A₁₆₅b (an antiangiogenic isoform of VEGF-A) concentrations with time to remission of AAV in a nationwide Japanese prospective follow-up cohort.

Methods: We collected samples from patients with AAV who were enrolled in the nationwide Japanese cohort study (RemIT-JAV-RPGN). We measured sVEGF-A and sVEGF-A₁₆₅b concentrations using enzyme-linked immunosorbent assays in 57 serum samples collected 6 months before and after initiation of AAV treatment. Patients were classified based on AAV disease subtypes: microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis (EGPA).

Results: Results revealed significant reductions in sVEGF-A and sVEGF-A₁₆₅b concentrations in patients with microscopic polyangiitis and EGPA, respectively. However, despite the comparable concentrations of sVEGF-A and sVEGF-A₁₆₅b during the 6 months of treatment in granulomatosis with polyangiitis patients, correlation analysis revealed that the differences in log₂-transformed concentrations of sVEGF-A and sVEGF-A₁₆₅b were inversely correlated with time to remission in granulomatosis with polyangiitis patients.

Conclusion: These results suggest that sVEGF-A and -A₁₆₅b can serve as potential markers of time to remission in patients with granulomatosis with polyangiitis.

Keywords: Antineutrophil cytoplasmic antibody-associated vasculitis; rapidly progressive glomerulonephritis; therapeutic efficacy; vascular endothelial growth factor-A; vascular endothelial growth factor-A165b.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / blood
Biomarkers / blood
Churg-Strauss Syndrome / blood
Cohort Studies
Female
Glucocorticoids / therapeutic use
Granulomatosis with Polyangiitis / blood*
Granulomatosis with Polyangiitis / therapy*
Humans
Immunosuppressive Agents / therapeutic use
Japan
Male
Microscopic Polyangiitis / blood
Middle Aged
Prospective Studies
Remission Induction
Vascular Endothelial Growth Factor A / blood*

Substances

Biomarkers
Glucocorticoids
Immunosuppressive Agents
VEGFA protein, human
Vascular Endothelial Growth Factor A