216.14: Validating a Cut-off of IgG Hypogammaglobulinemia as a Risk Factor of Severe Infection in Solid Organ Transplantation

Abstract

Backgound and aims: Severe infection is a leading cause of morbidity and mortality in solid organ transplantation. IgG hypogammaglobulinemia has been previously investigated in single and multicenter studies in distinct solid organ transplantations as a predictor of infection. We aimed to validate the IgG cut-off of 600 mg/dl as a risk factor of severe infection in solid organ transplantation. The potential utility of this biomarker is that this can be modulated by therapeutic intervention. Materials and Methods: 538 heart, liver or kidney recipients were analysed in a prospective study performed in 2 centers. During a follow-up during the first 6 months after solid organ transplantation 298 (55.4%) patients developed at least one episode of severe infection the majority of which were bacterial infections. As a secondary outcome we retrospectively analysed the impact of IgG hypogammaglobulinemia early after transplantation on the rate of death. Survival analysis was performed by Kaplan-Meier. Risk for development of severe infection was also performed by logistic regression analysis. Results: The rate of decrease of IgG after transplantation was similar in both participating centers. Cumulative survival without severe infection during the first 6 months after transplantation was lower in solid organ transplantation recipients with IgG hypogammaglobulinemia defined as IgG < 600 mg/dl at days 7 or 30 after transplantation (Log Rank 5.22, p=0.022). IgG hypogammaglobulinemia was associated with higher rates of death after solid organ transplantation (Log Rank 5.75, p=0.017). In logistic regression analysis IgG hypogammaglobulinemia was significantly associated with risk of severe infection (OR 1.635, p=0.040, 95%CI 1.022-2.615). IgG hypogammaglobulinemia was a risk factor of death (OR 1.078, p= 0.011, 95%CI 1.180 – 3.668). We performed an immunological score for development of severe infection composed of pre transplant monocytes < 7% (2 points), IgG hypogammaglobulinemia (2 points), CD4 <400 cells/uL at day 30 (2 points), C3 < 60 mg/dl at day 30 (2 points) and CRP > 3 mg/dl at day 30 (2 points). In those patients with 4 or more points, OR for development of infection was 2.89 (95% CI 1.641 – 5.123; p<0.001). Conclusion: IgG hypogammaglobulinemia (defined as IgG < 600 mg/dL early after transplantation) is associated with risk of severe infection in solid organ transplantation. This cut-off should be taken into account in future clinical trials that evaluate the impact of the modification of this risk factor by adding intravenous immunoglobulin to these patients to prevent severe infection. An immunological score combining IgG hypogammaglobulinemia and other innate and acquired immunity parameters could be a better way to identify the risk for development of severe infection in solid organ recipients.