Resolution of hypogammaglobulinemia in a patient with immunodeficiency and decompensated cirrhosis

Abstract

The liver plays an important but understudied role in humoral immunity. We present a case of a 62-year-old male with common variable immunodeficiency (CVID) previously on immunoglobulin replacement therapy (IGRT) and Hennekam syndrome. At the time of diagnosis 17 years ago, he was experiencing recurrent sinopulmonary infections. He was found to have low immunoglobulin (Ig) levels: IgG was 296 mg/dL, IgAwas 6 mg/dL, and IgM was 76 mg/dL. He had nonprotective titers to S. pneumoniae despite vaccination with pneumococcal polysaccharide vaccine-23. Immune workup was also notable for T cell lymphopenia requiring prophylactic trimethoprim/sulfamethoxazole. Even with IGRT, serum IgG remained in the 400–500 mg/dL range, likely due to “third-spacing” from his lymphatic disorder. However he did not have any significant infections while on IGRT. In the past year the patient was diagnosed with cirrhosis secondary to non-alcoholic steatohepatitis, and is undergoing liver transplant evaluation. He self-discontinued IGRT at the time of diagnosis. Six months after stopping IGRT the patient remained infection-free. Immunoglobulin panel revealed a serum IgG of 819 mg/dL, the patient’s highest recorded value.Elevated serum immunoglobulin levels have been observed in patients with advanced liver disease, however the pathophysiology is poorly understood. Several theories have been proposed. First, there is diminished ability of the failing liver to trap and clear antigens and endotoxins absorbed from the gut. The presence of portal hypertension results in increased systemic circulation of antigens and endotoxins, which leads to increased stimulation of plasma cells and thus increased production of immunoglobulin. In addition, patients with advanced liver disease have shown decreased capacity to catabolize immunoglobulin. Interestingly, at follow up the patient was found to have protective titers to S. pneumoniae, likely reflecting lingering antibodies from his infusions months prior. The patient is being monitored off IGRT.To our knowledge, this is the first case of resolving hypogammaglobulinemia in an immunodeficient patient with cirrhosis. It demonstrates an unforeseen consequence of cirrhosis in a patient requiring IGRT for CVID. Increases in IgG and IgM preceded transaminitis, highlighting the importance of delving deeper when there is unexplained resolution of hypogammaglobulinemia.