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Detection and clinical impact of human leukocyte antigen antibodies in lung transplantation: A systematic review and meta‐analysis

There is significant variability in lung transplant centers’ approach to HLA antibodies, creating heterogeneity regarding their clinical significance. Some institutions use beads coated with multiple HLA to screen candidate sera and then use single antigen bead (SAB) to determine antibody identity if the pre‐screen is positive. Other centers do not pre‐screen, using SAB alone, which may detect low‐level antibodies of unknown significance. The primary objective of this study was to review the current literature to identify sources of heterogeneity in the identification of pre‐ and post‐lung transplant HLA antibodies, particularly regarding antibody‐detection methods. A random effects model meta‐analysis was used to evaluate the relationship between pre‐transplant HLA antibodies and the development of de novo donor‐specific antibodies (dnDSA) and dnDSA and chronic lung allograft dysfunction (CLAD). Each outcome was stratified by the method of antibody detection (pre‐screen followed by SAB vs SAB alone). We identified 13 cohort studies with a total of 3039 patients. The use of pre‐screening followed by SAB testing and the use of induction immunosuppression were associated with lower prevalence of dnDSA. Patients with pre‐transplant HLA antibodies were more likely to develop dnDSA (hazard ratio [HR] = 1.49, 95% confidence interval [CI]: 1.19‐1.86, P < .001). dnDSA was associated with CLAD (HR = 2.02, 95% CI = 1.37‐2.97, P < .001). When considering studies using SAB alone, however, pre‐transplant antibody status was no longer associated with dnDSA and dnDSA was no longer associated with CLAD. Based on the current literature, SAB‐alone testing may detect less clinically relevant antibodies than pre‐screening followed by SAB.