Intravenous Immunoglobulin Replacement Therapy in Solid Organ Transplantation with Severe Infections and Secondary Antibody Deficiency: Proof of Concept
Javier Carbone1,2, Juan Fernandez-Yañez4, Judith Montanchez2, Eduardo Zatarain4, Joaquin Navarro2, Maria Rodriguez-Ferrero5, Fernando Anaya5, Magdalena Salcedo6, Ainhoa Fernandez6, Patricia Muñoz3, Maricela Valerio3, Elizabeth Sarmiento2.
1Immunology, Oftalmology and ORL Department, Complutense University, Madrid, Spain; 2Transplant Immunology Group. Immunology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 3Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 4Cardiology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 5Nephrology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 6Gastroenterology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
Background: Secondary antibody deficiency is a risk factor of severe infection in solid organ transplantation. Very few studies have previously evaluated the potential role of IgG replacement in solid organ recipients with IgG hypogammaglobulinemia (HGG) at the time of a severe infectious complication. We evaluated the impact of therapeutic intervention of intravenous immunoglobulin (IVIG) in solid organ recipients with severe infections and HGG on clinical outcomes.
Methods: Retrospective analysis of prospectively collected data of 60 patients in a single center. All patients were hospitalized because of severe infections or developed a severe infection during a hospitalization in the post-transplantation period (June 2015-June 2017) and were found to have HGG (serum IgG<600 mg/dL). 32 patients 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) and 28 patients were treated with only conventional antimicrobial therapy. IVIG was administered at a dose of 300-400 mg/kg/month. Clinical outcome was the incidence of new infectious complications and deadly infections during a 6-month follow up.
Results: Distribution of solid organ recipients was as follows: Heart 37, liver 10, kidney 13. The incidente of re-infection was significantly higher in patients with HGG that were not treated with IVIG as compared with IVIG-treated patients (78.6% vs 28.1%, two-sided chi-square test p<0.001). Size effect (No IVIG vs IVIG) was an odds-ratio 9.40 (95%CI 2.86-30.71, p<0.001). The incidence of deadly infections was also significantly higher in patients with HGG that were not treated with IVIG (35.7% vs 12.5%, p<0.034, odds ratio 8, 95%CI 1.7-38.5, p=0.009).
Conclusions: IVIG replacement therapy in solid organ recipients with severe infections and HGG is associated with a lower rate of re-infection and deadly infections. A randomized clinical trial is warranted to further evaluate this potential effect of IVIG in solid organ transplantation.
Instituto de Salud Carlos III. Project FIS Clinical Trial EC11084. With participation of FEDER funds. A way of making Europe..
