Immune monitoring of anti cytomegalovirus antibodies and risk of cytomegalovirus disease in heart transplantation Elizabeth Sarmiento a, ⁎, Nallibe Lanio a , Antonio Gallego a , Juan Rodriguez-Molina a , Joaquin Navarro a , Juan Fernandez-Yañez b , Jesus Palomo b , Cesar Rodríguez-Hernández c , Manuel Ruiz d , Roberto Alonso e , Eduardo Fernandez-Cruz a , Javier Carbone a a Transplant Immunology Group, Immunology Department, University Hospital Gregorio Marañon, Madrid, Spain b Cardiology Department, University Hospital Gregorio Marañon, Madrid, Spain c Biochemistry Department, University Hospital Gregorio Marañón, Madrid, Spain d Cardiac Surgery Department, University Hospital Gregorio Marañón, Madrid, Spain e Microbiology Department, University Hospital Gregorio Marañon, Madrid, Spain abstract article info Article history: Received 26 June 2008 Accepted 25 September 2008 Keywords: Heart transplantation Cytomegalovirus Gancyclovir Risk factors hypogammaglobulinemia Anti-CMV antibodies We sought to determine whether quantitative assessment of anti-cytomegalovirus (CMV) antibodies could be useful to identify patients at risk of cytomegalovirus (CMV) disease after heart transplantation (HT). 75 patients who underwent HT at a single health care center were prospectively studied. Induction therapy included 2 doses of daclizumab and maintenance tacrolimus (n = 42) or cyclosporine (n = 29), mycophenolate mofetil and prednisone. All patients received prophylaxis with gancyclovir or valganciclovir. Anti-CMV intravenous immunoglobulin (CMV-IG) was added in high risk patients (CMV D+/R- serostatus). Serial determinations of anti-CMV antibodies, immunoglobulins (IgG, IgA, IgM) and IgG-subclasses were analysed. CMV infection was based on detection of the virus by antigenemia. CMV disease consisted of detection of signs or symptoms attributable to this microorganism. Ten patients (13.3%) developed CMV disease. Mean time of development of CMV disease was 3.4 ± 1.6 months. In Cox regression analysis, patients with low baseline anti-CMV titers (b 4.26 natural logarithm of titer, RH: 8.1, 95%CI: 1.93–34.1, p =0.004) and recipients with 1-month post-HT IgG hypogammaglobulinemia (IgG b 500 mg/dl, RH: 4.49, 95%CI: 1.26–15.94, p = 0.02) were at higher risk of having CMV disease. Despite use of prophylactic CMV-IG, D+/R- patients showed significantly lower titers of anti- CMV antibodies at 7 d, 30 d and 90 d post HT as compared with HT recipients without infections. Four out of 6 of these patients developed late CMV disease. Monitoring of specific anti-CMV antibodies on the bedside warrants further evaluation as a potential tool to identify heart transplant recipients at higher risk of CMV disease. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Despite antiviral prophylactic and pre-emptive therapy, cytome- galovirus (CMV) infection remains the most important infectious complication in heart transplantation (HT), currently affecting 7%– 35% of patients [1,2]. Occult infection [3], delayed-onset primary CMV disease [4], gancyclovir-resistant disease [5], and the potential role of this microorganism as a cofactor in allograft vascular disease [6–8], are matters of concern. On the other hand, CMV infection may predispose patients to opportunistic infections and malignancies [9]. All these complications warrant a better strategy for CMV prevention. IgG hypogammaglobulinemia has been recently identified as a marker of the net state of immunosuppression in HT and severe infections have been reported in hypogammaglobulinemic patients [10–12]. We have previously demonstrated that IgG monitoring is useful to detect patients at risk of infection after HT [13,14]. This study was conducted to investigate if quantitative assessment of anti-CMV antibodies could be useful to identify patients at higher risk for developing CMV disease after HT. 2. Patients and methods We performed a prospective follow-up study in a cohort of 75 consecutive heart transplant recipients admitted in our General Hospital of the Community of Madrid, since November 2002 up to September 2007. Patients were included in the study at different times. As a result the length of follow-up period differs among pa- tients. They were scheduled to return at regular intervals for clini- cal evaluation and laboratory tests after transplantation. Etiology of transplantation was ischemic cardiopathy (n =37, 49.3%), dilated car- diomyopathy (n =13, 17.3%), valvular heart disease (n =10, 13.3%), International Immunopharmacology 9 (2009) 649–652 ⁎ Corresponding author. Immunology Department, University Hospital Gregorio Marañon, Dr. Esquerdo 46, 28007, Madrid, Spain. Tel.: +34 914265180; fax: +34 91 5866698. E-mail address: esarmiento.hgugm@salud.madrid.org (E. Sarmiento). 1567-5769/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.intimp.2008.09.013 Contents lists available at ScienceDirect International Immunopharmacology journal homepage: www.elsevier.com/locate/intimp