Increased erythrocyte C4D is associated with known alloantibody and autoantibody markers of antibody-mediated rejection in human lung transplant recipients

An increased percentage of the erythrocyte-bound complement degradation product C4d (E-C4d) fraction was found in the peripheral circulation of 22 post-lung transplant (LTx) recipients compared with 15 healthy controls. Results are expressed in mean ± SD.

Increased %E-C4d in post-LTx recipients with donor-specific antibody (DSA) compared with DSA− patients with or without detectable anti-human leukocyte antigen (HLA) antibodies (Abs). Group 1 comprised 4 patients with DSA, Group 2 comprised 5 patients who developed anti-HLA but not DSA, and the 13 patients in Group 3 remained negative for both DSA and anti-HLA. There was a significant difference between DSA and anti-HLA+ patients (Group 1 vs 2; p = 0.02), DSA and anti-HLA− patients (Group 1 vs 3; p = 0.03), and DSA and non-DSA patients (Group 1 vs Group 2 + 3; p = 0.02). The difference between anti-HLA+ (Group2) and anti-HLA- patients (Group 3) was not significant (p = 0.1). %E-C4d is higher in DSA+ LTx patients compared with those who are DSA− (p = 0.02).

Increased %E-C4d in post-lung transplant (LTx) recipients with high antibody titers to self-antigens, K-α-1-tubulin (KA1T) and collagen V (Col-V). Of 22 LTx recipients, 11 patients had a high titer to KA1T (>298 μg/ml) and 3 patients had a low titer to KA1T (<90 μg/ml). Similarly, 14 patients had a high tier to Col-V (>195 μg/ml) and 3 patients had a low titer to Col-V (<27 μg/ml). Mean E-C4d in recipients with high KA1T titers was 23%+10.5%; in the low KA1T titer group, it was 3.4% ± 1.4% (p = 0.02). Similarly, E-C4d in recipients with high Col-V titers was 22.9% ± 9.7%; in the low Col-V titer group, it was 3.4% ± 1.4% (p = 0.03). Mean data are shown with the standard deviation.

Increased %E-C4d in post-lung transplant (LTx) recipients who demonstrated deposition of C3d on lung biopsy tissue. Of 22 lung transplant recipients, 9 patients were C3d+ and 13 patients were C3d−. Mean E-C4d in C3d+ patients was 26.1+10.1. Mean E-C4d in C3d− patients was 15.5 ± 6.8 (p = 0.01). The higher %E-C4d noted in patients who were C3d+ on immunohistological staining further demonstrated that increased E-C4d is a biomarker for antibody-mediated rejection in post-LTx patients. Mean data are presented with the standard deviation.