Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections
Sarmiento E (1), Jaramillo M (1), Calahorra L (1), Fernandez-Yañez J (2), Gomez-Sanchez M (3), Crespo-Leiro MG (4), Paniagua M (4), Almenar L (5), Cebrian M (5), Rabago G (6), Levy B (6), Segovia J (7), Gomez-Bueno M (7), Lopez J (8), Mirabet S 9, Navarro J (1), Rodriguez-Molina JJ (1), Fernandez-Cruz E (1), Carbone J (10).
(1) Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
(2) Cardiology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
(3) Cardiology Department, Hospital Universitario Doce de Octubre, Madrid, Spain.
(4) Cardiology Department, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain.
(5) Heart Failure and Heart Transplant Unit, Cardiology Department, Hospital Universitario La Fe, Valencia, Spain.
(6) Heart Surgery Department, Clínica Universidad de Navarra, Pamplona, Spain.
(7) Heart Failure and Cardiomyopathy Unit, Heart Failure and Heart Transplant Section, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
(8) Heart Failure and Heart Transplant Unit, Hospital Clínico Universitario, Valladolid, Spain.
(9) Cardiology Department, Sant Pau Hospital, Barcelona, Spain.
(10) Clinical Immunology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain
New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections.
We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV).
To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection.
During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease.
At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection.
Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection.
CITATION J Heart Lung Transplant. 2016 Oct 17. pii: S1053-2498(16)30362-X. doi: 10.1016/j.healun.2016.10.004