The leading cause of death in the first year post-lung transplantation is infection. Efforts to reduce mortality from infectious complications include prophylaxis against the most common opportunistic pathogens. Herein we report a case of significant hypogammaglobulinemia following lung transplantation complicated by frequent infections and treated successfully with intravenous gammaglobulin.
SB was a 52 year-old female with extensive emphysema. She received a left single lung transplant on March 11, 2002. Her immunosuppressive regimen consisted of cyclosporine, mycophenolate mofetil and prednisone. Prophylactic medications included Bactrim, IV Ganciclovir for 90 days followed by oral valganciclovir, IV CMV-hyperimmune globulin and Nystatin oral suspension. Three days post-discharge she experienced increasing dyspnea, chest pain and fevers. A bronchoscopy with transbronchial biopsy revealed minimal acute rejection. She was treated for acute rejection with 1 gram of methylprednisolone for three days, and had resolution of her fever and hypoxemia. On May 13, 2002, the patient presented with three days of fever and cough. Blood and sputum cultures were positive for methicillin-resistant Staphylococcus aureus. The patient completed a two week course of intravenous vancomycin.On August 7th, bronchoscopy with endobronchial biopsies of a lesion at the anastomosis revealed Aspergillus infection. Surveillance bronchoscopy performed September 17, 2002 revealed moderate acute cellular rejection (Grade A2B3). The patient was treated with 1 gram of methylprednisolone for three days. One week later, the patient developed worsening dyspnea, fever and cough. A chest radiograph revealed opacification of the left lower lobe. Bronchoscopy performed was positive for MRSA. On October 10th serum IgG was 443 mg/dl. A sample of preoperative serum was obtained from storage; IgG was 614 mg/dl. The patient was started on intravenous gammaglobulin (Gamimmune) 20 grams every four weeks. She has not experienced any subsequent episodes of infection or rejection.DISCUSSION: Immunoglobulin deficiency in solid organ transplantation is poorly described. In the only article on hypogammaglobulinemia in lung transplant recipients, Goldfarb et al reported on 67 patients with post-transplant humoral immune surveillance data. Forty-seven patients had IgG levels less than 600 mg/dl, and 25 had levels less than 400 mg/dl. They document a significantly increased incidence of infections in the “lowest IgG” group (IgG < 400 mg/dl), with invasive aspergillosis occurring only in the hypogammaglobulinemic groups (3).This group published a study of nine cardiac transplant recipients with severe post-transplant HG (IgG < 350 mg/dl) who received pre-emptive immunoglobulin replacement therapy (5), and compared these patients to eleven patients with severe HG from a prior study. There was a significant decrease in clinical opportunistic infections. This study is the first to demonstrate the clinically utility of immunoglobulin replacement therapy in severe HG following solid organ transplantation.Our patient did not suffer from clinical CMV infection. This probably was the result of intensive and prolonged prophylaxis. Her only opportunistic infection was aspergillosis of the airway and otherwise presented with staphylococcal disease. Although the targets of immunosuppression regimens are the T cell dependent pathways, calcineurin inhibitors, corticosteroids and purine antagonists can all affect B cell proliferation and immunoglobulin production (6, 7). A hypothesis can be made that the observed IgG deficiency results from the indirect action of T cell inhibition. However, given the overlap between T cell and B cell receptor/intracellular signaling, it would be likely that the immunosuppressive agents are exerting a direct effect on B cell function.
Hypogammaglobulinemia is a significant factor contributing to the risk of infection following solid organ transplantation. Further studies are warranted to characterize the risk factors for the development of HG, and to assess the benefit of immunoglobulin replacement on infection risk and patient survival.
J.S. Wilt, None.