Purpose: Survival among lung transplant recipients (LTRs) remains poor compared to other solid organs.The presence of donor-specific antibodies (DSA) directed against donor human leukocyte antigen (HLA) has been associated with early and high-grade chronic lung-allograft dysfunction (CLAD) and death after lung transplantation.Some DSA characteristics, such as complement fixation in vitro, may be more harmful than others.We hypothesized that C1q+ DSA is associated with increased CLAD in LTRs.

Methods:This is a retrospective cohort study of adult LTRs.Patients were tested by Luminex Single Antigen Bead (SAB) IgG and C1q. IgG-SAB MFI>1000 and C1q-SAB MFI>500 were considered positive.Patients were grouped as no DSA, C1q-DSA, or C1q+DSA.The primary outcome was incidence of CLAD at 1 and 3 years.Secondary outcomes included survival at 1 and 3 years.The primary outcome was assessed using logistic regression.Survival was assessed using Kaplan-Meier method with log rank conversion.

Results:582 LTRs were included.355 (61%) did not develop DSA, 227 (39%) developed DSA and 43 (19% of all DSA) of these developed C1q+DSA.CLAD rates were 14.0% at 1 year and 31.9% at 3 years.Compared to no DSA, C1q+DSA was associated with an increased likelihood of CLAD at 1 year on curde (p<0.05) and adjusted analysis (OR: 2.36, 95% CI: 1.00-5.57, p<0.05) and trended toward significance at 3 years on crude (p=0.27) and adjusted analysis (OR: 1.80, 95%CI: 0.68-4.75, p=0.23), when controlling for age, gender, and single vs double LT.Compared to C1q-DSA, C1q+DSA was associated with an increased likelihood of CLAD at 1 year on crude (p=0.03) and adjusted analysis (OR: 2.70, 95% CI: 1.05-6.94, p=0.04) and 3 years on crude (p=0.04) and adjusted analysis (OR: 2.96, 95%CI: 1.04-8.45, p=0.04), when controlling for covariates.There were no significant differences in the likelihood of CLAD between the no DSA and C1q-DSA groups on univariable or multivariable analyses.Mortality rates were 8.9% at 1 year and 20.8% at 3 years.There was no significant difference in mortality between any of the groups.

Conclusions:C1q+DSA formation post-LT was associated with increased rates of CLAD at 1 and 3 years.Multicenter studies examining larger cohorts are necessary to evaluate the relationship between C1q+DSA and other relevant clinical outcomes including mortality.

CITATION INFORMATION: Ensor C., Iasella C., Mangiola M., Marrari M., Morrell M., Shigemura N., DCunha J., McDyer J., Zeevi A. Complement Fixing Donor-Specific Antibodies Are Associated with Increased Risk of Chronic Lung Allograft Dysfunction after Lung Transplantation Am J Transplant. 2017;17 (suppl 3).

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