Defining Secondary Antibody Deficiency After Heart Transplantation

Abstract

Post transplant severe hypogammaglobulinemia (defined as IgG < 400 mg/dL) has been found to be a risk factor of bacterial, viral and fungal infection in solid organ transplantation according to single center, multicenter and metanalysis studies. In the present study we report on the concentrations of different specific antimicrobial antibodies in heart recipients that were found to have severe hypogammaglobulinemia after heart transplantation to further characterize secondary antibody deficiency in these patients as a potential indication of intravenous immunoglobulin therapy. In a prospective single center follow-up study we evaluated in 131 heart recipients the kinetics of total IgG and of specific antibody concentrations at baseline (pre-transplant) and day 7 and 30 after transplantation. IgG was performed by nephelometry. Specific antibodies included: IgG, IgA and IgM anti-pneumococcal polysaccharide (whole 23 serotypes), IgG anti-CMV, IgG anti-HBs, IgG anti- tetanus toxoid, IgG anti-varicella zoster, IgG anti-salmonella typhi and IgG anti-haemophilus influenzae type B antibodies. All specific antibodies were tested by ELISA tests. During follow-up, 17 (12.9%) patients developed severe IgG hypogammaglobulinemia at least in one study point after transplantation. These patients were found to have significantly lower concentrations of IgG anti-pneumococcal polysaccharide antibodies [at day 7, p=0.002, day 30, p=0.010], IgG anti-HBs [day 7, p=0.001], IgG anti-CMV [day 7, p=0.046], IgG anti-varicella zoster [day 7, p=0.042], as compared with patients without severe hypogammaglobuliemia. Severe hypogammaglobulinemia was a risk factor of severe infection (OR 6.20, 95% confidence interval 2.09-18.39, p=0.0010) and a risk factor of death (OR 4.86, 95% confidence interval 1.39-16.89, p=0.01). Secondary severe IgG hypogammaglobulinemia early after heart transplantation is associated with specific antibody deficiency that could further explain why these patients are at a higher risk of developing severe infections. The association of this secondary antibody deficiency status with higher rates of death is a rationale for considering the role of immune replacement therapy in this setting. Instituto de Salud Carlos III. Project FIS 1501472. With participation of FEDER funds. A way of making Europe.