Abstract: SA-PO241

Urinary AlphaM Subunit of Integrin Mac-1 Associates With Glomerular Inflammation in Lupus Nephritis

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Kitagawa, Akimitsu, Nagoya University Graduate School of Medicine, Nagoya-shi,Aichi, Japan
  • Tsuboi, Naotake, Nagoya University Graduate School of Medicine, Nagoya-shi,Aichi, Japan
  • Kamimura, Yutaka, Nagoya University Graduate School of Medicine, Nagoya-shi,Aichi, Japan
  • Katsuno, Takayuki, Nagoya University Graduate School of Medicine, Nagoya-shi,Aichi, Japan
  • Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya-shi,Aichi, Japan
Background

One of the pathogenesis of glomerulonephritis is glomerular accumulation of leukocytes. Integrin Mac-1 is composed of a unique α (αm; CD11b) complexed to a common β2 subunit (CD18) on neutrophils and monocytes/macrophages. Mac-1 has been demonstrated to support various immunological functions on glomerular endothelium including leukocyte recruitment and immune-complex clearance. Interestingly, leukocytes have been shown to release Mac-1 from the surface upon cell activation under inflammatory conditions. In the current study, we evaluated the association of urine levels of CD11b (U-CD11b) with histological disease activity in experimental animals with glomerulonephritis and patients with various glomerular diseases, in particular lupus nephritis (LN).

Methods

Antibody-mediated glomerulonephritis was induced by rabbit anti-mouse nephrotoxic serum in male C57BL/6J mice (NTS-GN). Urine and kidney samples from NTS-GN mice and from 272 patients with glomerular diseases including LN between 2008 and 2014 in Nagoya University were subjected to the study. Urinary concentrations of CD11b, hemoglobin scavenger receptor CD163 (U-CD163), and MCP-1 (U-MCP-1) were measured by ELISA. Glomerular CD11b+ cells for neutrophils and monocytes/macrophages were also immunohistologically analyzed. In 118 LN patients, histological disease activity was evaluated semiquantitatively using the biopsy activity index (BAI).

Results

U-CD11b was evident on day 14 and elevated until day 21 in NTS-GN mice. In human patients, U-CD11b levels were significantly increased in ANCA-associated vasculitis and LN group, particularly in the ISN/RPS class IV. In LN, the number of glomerular CD11b+ cells was correlated with U-CD11b concentration (r=0.547) and BAI (r=0.643). It is of note that corticosteroid treatment significantly reduced U-CD11b excretion associated with the disease amelioration both in experimental animals with NTS-GN and human LN patients. In the ROC curve generated to predict ISN/RPS class III and IV subpopulations, area under the curve of U-CD11b (0.904, sensitivity: 89.7%, specificity:84.7%) was greater than that of U-CD163 and U-MCP-1.

Conclusion

These data collectively suggest that U-CD11b can be a useful biomarker for prediction of histological disease activity in LN.

Funding

  • Government Support - Non-U.S.