Megumi Oshima1,2, Yasunori Iwata3,4,5, Kengo Furuichi1,2, Norihiko Sakai1,2, Miho Shimizu1,2, Akinori Hara1,2, Shinji Kitajima1,2, Tadashi Toyama1,2, Yasuyuki Shinozaki1,2, Akihiro Sagara1,2, Eri Umeda1, Shuichi Kaneko2, Satoko Arai6, Toru Miyazaki6, Takashi Wada1,7. 1. Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan. 2. Department of Disease Control and Homeostasis, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan. 3. Division of Nephrology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan. iwata-knz@umin.ac.jp. 4. Department of Disease Control and Homeostasis, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan. iwata-knz@umin.ac.jp. 5. Division of Infection Control, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan. iwata-knz@umin.ac.jp. 6. Laboratory of Molecular Biomedicine for Pathogenesis, Faculty of Medicine, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo, Japan. 7. Department of Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
Abstract
BACKGROUND: Apoptosis inhibitor of macrophage (AIM) expressed on macrophages prolongs inflammation by protecting macrophages from apoptosis. Most circulating AIM co-exists with immunoglobulin M (IgM). AIM's pathophysiological role in relation to IgM remains unclear. Here we evaluated the glomerular expression/deposition of AIM and IgM in the kidney using immunohistochemistry and its associations with clinical manifestations in 43 patients with biopsy-confirmed kidney diseases. METHODS: Kidney biopsy tissue from all patients was immunostained for AIM and IgM. Staining patterns and percent stained areas within the glomeruli were determined. Cells expressing AIM were identified by co-staining with macrophage and endothelial cell surface markers. Correlations between staining results and clinical parameters were evaluated using univariate and multivariate analyses. RESULTS: AIM was deposited in various areas, such as mesangial and capillary area. A part of AIM expression was localized to CD68-positive macrophages in the glomerulus. Amount of glomerular expression was positively correlated with urinary protein in patients with severe proteinuria (urinary protein ≥0.5 g/day) and kidney dysfunction [estimated glomerular filtration ratio (eGFR) <60 ml/min/1.73 m2]. Urinary protein was higher in patients exhibiting overlapping glomerular expression of AIM and IgM. Annual eGFR decline rate negatively correlated with AIM-positive area. AIM-positive area and initial serum creatinine were independently associated with decreased kidney function. CONCLUSION: AIM expression in the kidney was associated with urinary protein and decline in kidney function. Co-expression with IgM appeared to exacerbate AIM's deleterious effects on kidney function. Combined glomerular AIM and IgM expression is a candidate prognostic index for kidney disease.
BACKGROUND: Apoptosis inhibitor of macrophage (AIM) expressed on macrophages prolongs inflammation by protecting macrophages from apoptosis. Most circulating AIM co-exists with immunoglobulin M (IgM). AIM's pathophysiological role in relation to IgM remains unclear. Here we evaluated the glomerular expression/deposition of AIM and IgM in the kidney using immunohistochemistry and its associations with clinical manifestations in 43 patients with biopsy-confirmed kidney diseases. METHODS: Kidney biopsy tissue from all patients was immunostained for AIM and IgM. Staining patterns and percent stained areas within the glomeruli were determined. Cells expressing AIM were identified by co-staining with macrophage and endothelial cell surface markers. Correlations between staining results and clinical parameters were evaluated using univariate and multivariate analyses. RESULTS: AIM was deposited in various areas, such as mesangial and capillary area. A part of AIM expression was localized to CD68-positive macrophages in the glomerulus. Amount of glomerular expression was positively correlated with urinary protein in patients with severe proteinuria (urinary protein ≥0.5 g/day) and kidney dysfunction [estimated glomerular filtration ratio (eGFR) <60 ml/min/1.73 m2]. Urinary protein was higher in patients exhibiting overlapping glomerular expression of AIM and IgM. Annual eGFR decline rate negatively correlated with AIM-positive area. AIM-positive area and initial serum creatinine were independently associated with decreased kidney function. CONCLUSION: AIM expression in the kidney was associated with urinary protein and decline in kidney function. Co-expression with IgM appeared to exacerbate AIM's deleterious effects on kidney function. Combined glomerular AIM and IgM expression is a candidate prognostic index for kidney disease.
Entities:
Keywords:
Apoptosis inhibitor of macrophage (AIM); IgM; Kidney disease
Authors: T Wada; H Yokoyama; K Furuichi; K I Kobayashi; K Harada; M Naruto; S B Su; M Akiyama; N Mukaida; K Matsushima Journal: FASEB J Date: 1996-10 Impact factor: 5.191
Authors: Derek Strassheim; Brandon Renner; Sarah Panzer; Richard Fuquay; Liudmila Kulik; Danica Ljubanović; V Michael Holers; Joshua M Thurman Journal: J Am Soc Nephrol Date: 2013-02-07 Impact factor: 10.121