Humoral immunity during acute cellular rejection in lung transplant patients

Humoral rejection is known to be important in renal and cardiac transplant outcomes but has not been well characterized in lung transplantation. To determine if there is concomitant humoral immunity activation during acute cellular rejection (ACR), we examined broncheoalveolar lavage (BAL) samples taken from patients before, during and after acute rejection, and from matched controls, for the presence of complement split products (CSP) iC3b, C3a and C4d by ELISA. Correlating clinical information was contained in an established database. 18 patients with ACR and 12 controls without ACR within 60 days of BAL sampling were well matched by number of days post-transplant (504 vs. 599), by type of transplant (53% vs. 50% single lung), by gender (53% vs. 42% female), by race (87% vs. 75% Caucasian) and by age (a median of 46 vs. 48 years). CSP values for the control group and the subject group at baseline (pre/post-rejection) did not differ. Infection did not influence CSPs in either controls or subjects. 85.7% of subjects had significant elevation in iC3b/C3a and/or C4d CSP levels (p<0.025), and half (50%) of these had significantly higher levels of all three CSPs (p<0.027) during ACR compared to baseline. Those subjects with elevated CSPs had a higher rate of recurrent ACR when compared to controls (86% vs. 33%, p=0.006), and a higher rate of BOS when compared to subjects with no CSP elevation (78.6% vs. 25%, p=0.045). None of the subjects with no CSP elevation had persistent ACR in marked contrast to the group of patients with elevated CSPs (0% vs. 43%, p=NS). In summary, 1/3rd of all subjects had significant elevation in all three CSPs during ACR, suggesting humoral immunity activation. Increased CSP levels in BAL at the time of ACR may be a marker for patients with risk for recurrent and/or persistent ACR and BOS. The importance of the humoral immune mechanism in the development of acute and chronic allograft warrants further investigation.