Hypogammaglobulinemia in pediatric liver transplant recipients

Abstract

Hypogammaglobulinemia has been reported after solid organ transplantation in adults, however immunoglobulin replacement [intravenous immunoglobulins (IVIG)] is only necessary in a minority of affected patients. We here present three pediatric patients with severe post-transplant hypogammaglobulinemia following liver transplantation (LTx) receiving a cyclosporine-based standard immunosuppression. Patient 1 was transplanted at the age of 10 months for biliary atresia. Eight weeks post-Ltx the serum IgG was 1.7 g/L. Patient 2 was transplanted at the age of 12 yr for acute liver failure. Four weeks post-Ltx the IgG dropped to 2.6 g/L. Patient 3 was transplanted at the age of 4 months for biliary atresia. Ten weeks post-Ltx severe hypogammaglobulinemia (IgG < 1.48 g/L) was diagnosed during a severe infectious complication. Patients 1 and 3 received a steroid bolus therapy for acute graft rejection. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were post-operatively in the normal range. There was no extensive loss of protein by ascites. IGIV were replaced in the three patients monthly without further complications. In two of the patients (1 and 3) IVIG therapy was discontinued 8 and 10 months after Ltx when the immunosuppression has been reduced and serum IgG concentrations were found in the normal range without further immunoglobulin replacement. Severe hypogammaglobulinemia is a rare phenomenon following pediatric LTx and seems to be mainly caused by immunosuppressive drugs, however, the exact underlying mechanisms are unclear. A screening for hypogammaglobulinemia is useful after pediatric LTx, especially in patients with an intensified immunosuppression. Moreover, further immunologic research in affected patients is necessary.

Immunoglobulin G Levels before and after Lung Transplantation

“…We and others have previously shown a significant association between severe HGG and adverse events after lung transplantation (6,11,14). In this study, however, we did not find a significant association between the absolute value of posttransplant IgG or posttransplant severe HGG with clinical outcomes such as infectious complications.…”

Pretransplant lymphocyte count predicts the incidence of infection during the first two years after liver transplantation

“…Some recent studies have analyzed the usefulness of the determination of intracellular concentrations of adenosine triphosphate in circulating CD4 + T lymphocytes after their stimulation in vitro 14, 15. Others have focused on the influence of humoral immunity of the recipient on the incidence of infection and overall survival in heart,3 renal,4 lung,5 or liver6, 7 transplant recipients. In a recent study, Carbone et al11 prospectively analyzed humoral and cellular immune monitoring in 46 OLT recipients, both at baseline and 3 months post‐transplant.…”

“…The risk of inadequate immune suppression resulting in rejection must be balanced against the risk of excess immune suppression and increased risk for life‐threatening infections and other adverse effects 2. Baseline alterations in specific and nonspecific humoral and cellular immunity may lead to an increased incidence of opportunistic infection among solid organ transplantation (SOT) recipients 3–7. It is well established that ESLD is associated with systemic metabolic changes that modify the patient's immune status 8–10.…”

High dose intravenous immunoglobulin treatment: Mechanisms of action

“…A recent addition to the indications for IVIg therapy is post‐transplant hypoglammaglubulinemia. This condition is being increasingly reported in liver, lung, and heart transplant patients 107–109. The exact mechanism is not clear, although heavy immunosuppression is likely to play a role.…”