The immunologic profile of patients with congenital heart disease complicated by protein-losing enteropathy (PLE) is undefined. The aim of this study was to assess the lymphocyte subpopulation and immunglobulin (Ig) pattern in patients with PLE complicating congenital heart disease. The immunologic profile of six patients with congenital heart disease complicated by PLE was compared to that of controls without PLE matched for age and cardiac interventions. Enteric protein loss was documented by Tc99m-labeled albumin scintigraphy. The lymphocyte subpopulations were enumerated using flow cytometry, whereas serum IgG, IgA, and IgM concentrations were measured by the turbidimetric technique. The cardiac diagnoses included complex cyanotic heart disease post-Fontan procedure (n = 3), and one each of tetralogy of Fallot, restrictive cardiomyopathy, and valvar pulmonary stenosis. In patients with PLE, the T lymphocyte (CD3+) count was significantly lower (300 +/- 186 vs 2070 +/- 1171/microl, p = 0.017); both the helper/inducer lymphocytes (CD4+) (127 +/- 158 vs 927+/- 377/microl, p = 0.006) and suppressor/cytotoxic lymphocytes (CD8+) (129 +/- 49 vs 850 +/- 695/microl, p = 0.057) reduced with reversal of CD4(+)/CD8(+) ratio (0.81 +/- 0.68 1.64 +/- 0.89, p = 0.027). Furthermore, IgG level was significantly reduced (5.12 +/- 2.84 vs 12.5 +/- 1.58 g/L, p = 0.005) and IgA level tended to be lower (1.36 +/- 1.37 vs 2.50 +/- 0.80 g/L, p = 0.095). In contrast, the B lymphocyte (CD19+) count (340 +/- 151 vs 618 +/- 427/microl, p = 0.25), natural killer cell count (CD16(+) 56(+) CD3(-)) (252 +/- 212 vs 276 +/- 251/microl, p = 0.85), and IgM level (0.98 +/- 0.59 vs 1.12 +/- 0.25 g/L, p = 0.67) were similar for both groups. None of the patients developed opportunistic or severe viral infections. Abnormal immunologic profile of both the cellular and humoral arms of the immune system occurs in patients with congenital heart disease complicated by PLE. Nonetheless, these abnormalities perhaps appear quantitative rather than qualitative in nature, although further functional studies of antibody production and lymphocyte proliferation assays are required to support this proposition.