Background. CD103 is displayed on the cell surface of alloreactive CD8 cytotoxic T lymphocytes (CTLs) and is a critical component for the intraepithelial homing of T cells. Because intratubular localization of mononuclear cells is a feature of acute cellular rejection of renal allografts, we explored the hypothesis that CD103 messenger (m)RNA levels in urinary cells predict acute rejection.
Methods. We collected 89 urine specimens from 79 recipients of renal allografts. RNA was isolated from the urinary cells, and we measured CD103 mRNA levels and a constitutively expressed 18S ribosomal (r)RNA with the use of real-time quantitative polymerase chain reaction assay.
Results. CD103 mRNA levels, but not 18S rRNA levels, were higher in urinary cells from 30 patients with an episode of acute rejection (32 biopsies and 32 urine samples) compared with the levels in 12 patients with other findings on allograft biopsy (12 biopsies and 12 urine samples), 12 patients with biopsy evidence of chronic allograft nephropathy (12 biopsies and 12 urine samples), and 25 patients with stable graft function after renal transplantation (0 biopsies and 33 urine samples) (P = 0.001; one-way analysis of variance). Acute rejection was predicted with a sensitivity of 59% and a specificity of 75% using natural log-transformed value 8.16 CD103 copies per microgram as the cutoff value (P = 0.001).
Conclusion. CD103 mRNA levels in urinary cells are diagnostic of acute rejection of renal allografts. Because CD103 is a cell surface marker of intratubular CD8 CTLs, a noninvasive assessment of cellular traffic into the allograft may be feasible by the measurement of CD103 mRNA levels in urinary cells.
Renal allograft failure is the fourth common cause of end-stage renal disease in the United States, and acute rejection is a major risk factor for the failure of allografts (1,2). Acute rejection is associated with a 20% reduction in the 1-year survival rate of cadaveric renal grafts and, despite refinements in immunosuppressive regimens, almost 35% of renal transplant recipients have an episode of acute rejection in the first posttransplant year (3,4). A better comprehension of the antiallograft repertory may help reduce the toll extorted by the acute rejection process.
We have reported that measurement of messenger (m)RNA for granzyme B and perforin in urinary cells is a noninvasive means of diagnosing acute rejection (5). We measured mRNA for granzyme B and perforin in view of the role of CD8 cytotoxic T cells (CTLs) in acute rejection (6) and the contribution of granzyme B and perforin to the lytic activity of CTLs (7).
This investigation measured the level of CD103 mRNA in urinary cells. CD103 defines a subset of CD8 CTLs and is a component of integrin αEβ7 responsible for binding to epithelial cells through E-cadherin (8,9). CD103-positive cells have been implicated in the acute rejection process by their association with tubulitis and by their presence in renal allografts removed for uncontrolled rejection (10,11). Because tubulitis is a histologic hallmark of acute rejection (12) and because intraepithelial lymphocytes display CD103 and normal renal tissue contains no intratubular CD103+ cells (13,14), we tested the hypothesis that CD103 mRNA would be present in high abundance in urinary cells obtained during an episode of acute rejection.