Increased lung allograft failure in patients with HLA-specific antibody

In this prospective study we report on a higher prevalence of lung allograft failure in patients with HLA-specific alloantibody, at two and four years of follow-up. Our report follows an increasing number of previous studies which have shown that anti-HLA alloantibody is a major risk factor for worse outcome in lung transplantation. Anti-class I and II HLA antibodies are reported to cause hyperacute rejection in lung allograft which can largely be avoided by a thorough analysis of sensitized candidates. Pre-transplant screening by multiple methods, including solid-phase/ single-antigen assays, can improve the sensitivity and specificity of virtual crossmatches and can identify additional acceptable mismatches resulting in an increased transplantability rate of highly sensitized candidates. Furthermore, posttransplant anti-HLA antibodies were strongly associated with a worse lung allograft outcome. Recipients that exhibited humoral allosensitization experienced an increased frequency of refractory acute rejection. The prevalence of lymphocytic bronchiolitis and decreased pulmonary function was also higher in antibody producers when compared to patients without anti-HLA antibody. The presence of specific C4d deposition in lung capillaries, as well as increased soluble C4d in bronchoalveolar lavage fluid, are markers of antibody-mediated rejection and are found especially in patients with mixed forms of rejection. Chronic lung allograft dysfunction, diagnosed as bronchiolitis obliterans syndrome, was higher in patients with anti-HLA antibody and was preceded by circulating antibody. The improved detection and characterization of anti-HLA antibody and the availability of additional therapeutic strategies to target the humoral alloimmune response should improve the clinical management of lung transplant recipients.