IgG Hypogammaglobulinemia is a Risk Factor of Cytomegalovirus Infection in a Multicenter Study in Kidney Transplantation
Javier Carbone1, Maria Luisa Rodriguez-Ferrero3, Marcos Lopez-Hoyos4, Boris Karanovic5, Manuel Arias6, Emilio Rodrigo6, Fernando Anaya3, Patricia Muñoz2, Alia Eworo2, Joaquin Navarro1, Pilar Catalan2, Roberto Alonso2, Elizabeth Sarmiento1.
1Clinical Immunology, Hospital General Universitario Gregorio Marañon, Madrid, Spain; 2Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañon, Madrid, Spain; 3Nephrology, Hospital General Universitario Gregorio Marañon, Madrid, Spain; 4Immunology, Hospital Universitario Marques de Valdecilla, Santander, Spain; 5Department of Internal Medicine, University of Zagreb School of Medicine, Zagreb, Croatia; 6Nephrology, Hospital Universitario Marques de Valdecilla, Santander, Spain
Background: IgG hypogammaglobulinemia has been demonstrated as a risk factor of severe infection in solid organ tranplantation in single center studies and metanalysis. Kidney transplant patients are more prone to CMV infection due to immunosuppressive therapy. IgG testing is suggested when CMV is difficult to control. We here present the results of a multicenter study with the aim to evaluate distinct humoral immunity biomarkers as potential predictors of CMV infection.
Materials and Methods: In a prospective multicenter study of a cohort of 212 patients in 2 centers in Spain who underwent kidney transplantation we identified patients who developed CMV infection during a 6 month follow-up after transplantation. Levels of IgG, IgM, IgA and complement C3 and C4 were prospectively measured in both centers using the routine laboratory. Assessment times were before transplantation, at day 7 and at day 30 after transplantation. Logistic regressión analysis was performed to assess potential biomarkers.
Results: During follow up 18 (8.5%) kidney recipients developed at least one episode of CMV infection. Day 30 IgG level was lower in patients who developed CMV infections after transplantation compared to patients without this complication (704±276 and 894±281%, respectively, p = 0.013). IgG level <700 mg/dL (IgG hypogammaglobulinemia) was significantly associated with risk for development of CMV infection in logistic regression analysis, RH 3.33, 95% CI 1.05-10.48, p = 0.04. Patients with hypogammaglobulinemia also disclosed a higher risk of developing recurrent infections (defined as 3 or more episodes caused by distinct pathogens, 24.1%), RH 2.4, 95% CI, 1.12-4.95, p=0.024).
Conclusion: The results obtained in this multicenter study suggest that lower levels of IgG are a risk factor for development of CMV infection and recurrent infections in kidney transplantation. IgG assessmnent is easily available, rapid and low cost. The inclusion of this biomarker in immunomonitoring protocols should be taken into account as well as in clinical guidelines.
Fondo de Investigacion Sanitaria. Project FIS 1501472. With participation of FEDER Funds, a new way of making Europe.. ISR global grant Grifols, California, USA.
