Hypogammaglobinemia in Patients Palliated with the Fontan Circulation: Implications for Cardiac Transplantation

Abstract

<h3>Purpose</h3> Protein-losing enteropathy (PLE) is a complication after the Fontan operation believed to result from lymphatic dysfunction. As a consequence of protein loss, patients can develop hypogammaglobinemia (HGG). PLE typically resolves following heart transplant, but changes in immunoglobulin levels are not well-described. HGG can increase peri-transplant infection risk and may impair the accurate assessment of pre-transplant antibodies against potential donors. In our case series, we present the changes in immunoglobulin levels among patients palliated with the Fontan procedure that later underwent heart transplant. <h3>Methods</h3> Patients who underwent Fontan with subsequent heart or heart-liver transplant were included (n=10). Variables included are listed in Table 1. Post-transplant IgG levels were collected at a minimum of 3 months post-transplant to avoid interference from high-dose steroids and higher doses of immunomodulation used in the immediate post-transplant period. HGG was defined as IgG < 700 mg/dL pre-transplant. <h3>Results</h3> The mean age at transplant was 22.3 years; 90% of patients were male. Three (30%) patients had HGG. Two had complete resolution of HGG. The third was treated with subcutaneous immunoglobulin before transplant. PLE resolved post-transplant. One of the patients with HGG had a persistent de novo donor-specific antibody in the setting of immunosuppression non-adherence. <h3>Conclusion</h3> In this case series, we present HGG as a consideration in patients palliated with Fontan. Due to the risk of infection, HGG may lead clinicians to reduce immunosuppression in the peri-transplant period. HGG may also impact the ability to detect the degree of sensitization as the panel of reactive antibodies relies on sufficient immunoglobulin titers against human-leukocyte antigen to identify unacceptable donors. Lastly, if HGG resolves predictably post heart-transplant, that may have further implications on early risk for rejection in this patient population.