Lower Rates of Death in Heart Recipients with Secondary Antibody Deficiency and Severe Infection After Therapy with Intravenous Immunoglobulin

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BackgroundSecondary antibody deficiency defined as IgG hypogammaglobulinemia (HGG) is a risk factor of severe infection in heart recipients. Single center studies (distinct induction protocols; various centers around the world); a multicenter prospective study; evaluation of reproducibility of IgG testing among centers and a metanalysis support the usefulness of this biomarker. Interventional studies evaluating the effect of the modification of the risk factor are necessary. We evaluated the impact of therapeutic intervention of intravenous immunoglobulin (IVIG) in heart recipients with severe infections and HGG on clinical outcomes.MethodsRetrospective analysis of prospectively collected data of 233 patients in a single center. 91 patients that developed severe infections in the post-heart transplantation period and were found to have HGG (serum IgG<600 mg/dL), received non-specific 5% IVIG in addition to conventional antimicrobial therapy with the aims of contributing to control of infection (secondary prevention of re-infection) and normalization of IgG (IgG>750 mg/dL). IVIG was administered at a dose of 300-400 mg/kg/month up to three months after infections were resolved (negative bacterial culture or CMV DNAmia). 142 heart recipients from the same center that where not treated with IVIG, were analyzed as controls.ResultsSevere infections included non pneumonic bacterial infection (30%), bacterial pneumonia (18%), CMV disaese + bacterial infection (12%), CMV disease + severe fungal infection (12%). Mean IgG level at the time of infection was 481 mg/dL (198-599 mg/dL). Mean time to the first IVIG infusion was 65.4 days (7-180 days). Normalization of IgG levels was obtained in 75 of 91 patients (82.4%) after addition of IVIG. Both groups were comparable in terms of demographic and clinical variables. IVIG treated recipients disclosed a lower rate of death (p=0.006). In multivariate regression analysis, IVIG use (RH 0.27, 95%CI 0.09-0.82, p=0.017), use of non-cytolitic induction (anti-CD25) vs cytolitic (ATG) (RH 0.28, 95%CI 0.09-0.82, p=0.017) and number of episodes of acute rejection (per each increase, RH 2.17, 95% CI 1.25-3.78, p=0.0062) remained in the final regression model as protective factors and risk factors respectively.ConclusionsPersonalized immunoguided intervention of IVIG in heart recipients with severe infections and HGG is associated with a lower rate of death during long term follow-up after heart transplantation. A multicenter randomized clinical trial is in due course in Spain to further evaluate this new IVIG indication.Instituto de Salud Carlos III. Project FIS Clinical Trial EC11084. With participation of FEDER funds. A way of making Europe.

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