Urinary levels of the leukocyte surface molecule CD11b associate with glomerular inflammation in lupus nephritis

Akimitsu Kitagawa, Naotake Tsuboi, Yuki Yokoe, Takayuki Katsuno, Hidekazu Ikeuchi, Hiroshi Kajiyama, Nobuhide Endo, Yuriko Sawa, Junya Suwa, Yutaka Sugiyama, Asaka Hachiya, Toshihide Mimura, Keiju Hiromura, Shoichi Maruyama

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Abstract

Noninvasive biomarkers of disease activity are needed to monitor response to therapy and predict disease recurrence in patients with glomerulonephritis. The leukocyte surface markers integrin Mac-1 and CD16b have been implicated in the pathogenesis of lupus nephritis (LN). Mac-1 comprises a unique α subunit (CD11b) complexed with a common β2 subunit, which are released along with CD16b from specific leukocyte subsets under inflammatory conditions including glomerulonephritis. We investigated the association of urinary CD11b and CD16b with histopathological activity in 272 patients with biopsy-proven glomerular diseases, including 118 with LN. Urine CD11b and CD16b were measured via enzyme-linked immunosorbent assay. Urinary levels of both markers were increased in LN, but only urinary CD11b was correlated with the number of glomerular leukocytes and with overall histopathological activity. In a subset of patients with samples available from the time of biopsy and subsequent clinical remission of LN, urinary levels of CD11b decreased with successful glucocorticoid treatment. Receiver-operating characteristic curve analysis demonstrated that urinary CD11b was superior to CD16b, the scavenger receptor CD163, and monocyte chemotactic protein-1 for the prediction of proliferative LN. In anti-mouse nephrotoxic serum glomerulonephritis, urinary CD11b correlated with histologic damage and decreased with corticosteroid treatment. In vitro, CD11b levels were decreased on activated mouse neutrophils displaying Fcγ receptor clustering and transendothelial migration, suggesting that leukocyte activation and transmigration are required for CD11b shedding in urine. Together, our results suggest that urinary CD11b may be a useful biomarker to estimate histopathological activity, particularly glomerular leukocyte accumulation, in LN.

Original languageEnglish
Pages (from-to)680-692
Number of pages13
JournalKidney International
Volume95
Issue number3
DOIs
Publication statusPublished - 03-2019

All Science Journal Classification (ASJC) codes

  • Nephrology

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    Kitagawa, A., Tsuboi, N., Yokoe, Y., Katsuno, T., Ikeuchi, H., Kajiyama, H., Endo, N., Sawa, Y., Suwa, J., Sugiyama, Y., Hachiya, A., Mimura, T., Hiromura, K., & Maruyama, S. (2019). Urinary levels of the leukocyte surface molecule CD11b associate with glomerular inflammation in lupus nephritis. Kidney International, 95(3), 680-692. https://doi.org/10.1016/j.kint.2018.10.025