TY - JOUR
T1 - Urinary levels of the leukocyte surface molecule CD11b associate with glomerular inflammation in lupus nephritis
AU - Kitagawa, Akimitsu
AU - Tsuboi, Naotake
AU - Yokoe, Yuki
AU - Katsuno, Takayuki
AU - Ikeuchi, Hidekazu
AU - Kajiyama, Hiroshi
AU - Endo, Nobuhide
AU - Sawa, Yuriko
AU - Suwa, Junya
AU - Sugiyama, Yutaka
AU - Hachiya, Asaka
AU - Mimura, Toshihide
AU - Hiromura, Keiju
AU - Maruyama, Shoichi
N1 - Funding Information:
NT received research grants from Bristol-Myers Squibb Foundation and Daiichi Sankyo Foundation of Life Science. All the other authors declared no competing interests.
Funding Information:
We thank Ms. N. Asano and Mr. N. Suzuki for excellent technical assistance. We are grateful for the generous support by a Grant-in-Aid for Scientific Research (C; 25461215) and (B; 17H04667) from the Ministry of Education, Culture, Sports, Science, and Technology (to NT), by a Grant-in-Aid for Progressive Renal Diseases Research, Research on Intractable Diseases, from the Ministry of Health, Labour, and Welfare of Japan (to ShM), and by Grant for Japan Agency for Medical Research and Development (JP18ek0109354 to NT and ShM). We also thank Bristol-Myers Squibb Foundation Grants and Daiichi Sankyo Foundation of Life Science for generous support (to NT).
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061369906&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061369906&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2018.10.025
DO - 10.1016/j.kint.2018.10.025
M3 - Article
C2 - 30712924
AN - SCOPUS:85061369906
VL - 95
SP - 680
EP - 692
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 3
ER -