| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Research Abstract |
FcγRIII (CD16) is found in two alternative forms, FcγRIIIa expressed on NK cells and macrophages (Mφ), and FcγRIIIb present on neutrophils. Both FcγRIIIs are released from the cell surface and these soluble forms (sFcγRIIIs) are present in plasma. We measured sFcγRIIIa and sFcγRIIIa^<Mφ> in plasma and also in urine from patients with proteinuria, with newly-developed anti-FcγRIIIa mAb, MKGR155 (mIgG1) and anti-FcγRIIIa^<Mφ> mAb MKGR14 (mIgM). In urine from healthy volunteer, total sFcγRIII (sFcγRIIIa plus sFcγIIIb) detected 11.4±6.1% of the value in plasma. In contrast, sFcγRIIIa (sFcγRIIIa^<NK> plus sFcγRIIIa^<Mφ>) and sFcγRIIIa^<Mφ>levels shown 1.0±0.6% and 6.3±3.5% of plasma value, respectively. From these results, neutrophils and monocytes/Mφ may infiltrate into renal tissue and then release soluble forms in urine in also healthy subjects. All three sFcγRIII levels in urine and also in plasma from patients with nephritis were higher than that in healthy volunteer. Plasma sFcγRIIIa^<Mφ> levels, but not total sFcγRIII or sFcγRIIIa levels, were increased extraordinary about 3.6 times higher than that of healthy volunteer. These high levels means patients have atherosclerosis. After adjustment for creatinine, urine total sFcγRIII levels were increased 1.6 times higher than that of healthy volunteer, sFcγRIIIa levels were 4.3 times and sFcγRIIIa^<Mφ> levels were 9.6 times. Urine total sFcγRIII levels, but not sFcγRIIIa or sFcγRIIIa^<Mφ> levels, were correlated with urine total protein, estimated glomerular filtration rate (eGFR) or 24h creatinine clearance (Ccr). These results suggested that monocytes/MΦ as well as NK cells infiltrate into renal tissue and were activated and then injured renal tissue. sFcγRIIIa and sFcγRIIIa^<Mφ> may be novel markers for the disease activity in nephritis.
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