C4d Deposits on the Surface of Red Blood Cells in Trauma Patients and Interferes with their Function


Objective Complement system is activated in patients with trauma. Although complement activation is presumed to contribute to organ damage and constitutional symptoms, little is known about the involved mechanisms. Because complement components may deposit on red blood cells (RBC), we asked whether complement deposits on the surface of RBC in trauma and whether such deposition alters RBC function.

Design A prospective experimental study

Setting Research laboratory

Subjects Blood samples collected from 42 trauma patients and 21 healthy donors

Intervention None

Measurements and Main Results RBC and sera were collected from trauma patients and control donors. RBC from trauma patients (n=40) were found to display significantly higher amounts of C4d on their surface by flow cytometry compared to normal RBC (n=17) (P<0.01). Increased amounts of iC3b were found in trauma sera (n=27) (vs. 12 controls, P<0.01) by ELISA. Incubation of RBC from universal donors (O,Rh-) with trauma sera (n=10) promoted C4d deposition on their surface (vs. 6 controls, P<0.05). Complement-decorated RBC (n=6) displayed limited their deformability (vs. 6 controls, P<0.05) in 2-dimensional microchannel arrays. Incubation of RBC with trauma sera (n=10) promoted the phosphorylation of band 3, a cytoskeletal protein important for the function of the RBC membrane (vs. 8 controls, P<0.05), and also accelerated calcium influx (n=9) and enhanced nitric oxide production (n=12) (vs. 4 and 8 controls respectively, P<0.05) in flow cytometry.

Conclusions Our study found the presence of extensive complement activation in trauma patients and presents new evidence in support of the hypothesis that complement activation products deposit on the surface of RBC. Such deposition could limit RBC deformability and promote the production of nitric oxide. Our findings suggest that RBC in trauma patients malfunction, which may explain organ damage and constitutional symptoms that is not accounted for otherwise by previously known pathophysiologic mechanisms.



red blood cell, trauma, C4d, complement, deformability, nitric oxide


Copyright 2014 Critical Care Medicine. This is a post-print version of a published paper that is available at: https://insights.ovid.com/ccme/201405000/00003246-201405000-00061 Recommended citation: Muroya, Takashi, Lakshmi Kannan, Ionita C. Ghiran, Sergey S. Shevkoplyas, Ziv Paz, Maria Tsokos, Jurandir J. Dalle Lucca, Nathan I. Shapiro, and George C. Tsokos. "C4d Deposits on the Surface of Red Blood Cells in Trauma Patients and Interferes with their Function." Critical care medicine 42, no. 5 (2014): e364. DOI: 10.1097/CCM.0000000000000231 This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.