This article describes the immunologic and pulmonary abnormalities and the chemical composition of pleural effusion fluid in a patient with intestinal lymphangiectasia as they are effected by therapeutic measures during a 7-year period. Lymphedema was first noticed in the patient at 3 years of age, and pleural effusions developed 7 years later. Thoracentesis demonstrated that the right pleural fluid was yellow, clear, and had the composition of lymph. The left pleural fluid was milky and had a higher triglyceride and lymphocyte content than the right pleural fluid. Complete removal of pleural fluid transiently increased total lung capacity to a maximum of 52% predicted. Strict dietary management with a low-fat and high-protein diet resulted in a transient partial reversal of circulating lymphopenia and low T cell concentration. This was accompanied by a decrease in lymphocyte and T cell concentration in the pleural fluid. Unstimulated mononuclear cells from pleural fluid synthesized increased amounts of DNA, and added mitogens or antigens further increased DNA synthesis. Dietary therapy had a minimal effect on this DNA synthesis. Despite circulating hypogammaglobulinemia, normal antibody activity was detected. The proportion of B cells in pleural fluid was greater than that in the circulation, and dietary therapy did not alter this difference. Pulmonary physiology improved during the initial 9-month period of diet therapy, but then the rate of fluid accumulation increased, causing respiratory compromise. Stability was achieved by a right-sided pleurodesis, followed 18 months later by a left pleurodesis with the addition of a shunt to provide internal lymph drainage.

Immunologic studies were performed in ten iron-deficient children, aged 12 to 30 months, before and after iron replacement. Chronic infection, malnutrition, and vitamin deficiency were excluded. Mean hemoglobin levels went from 8.2 +/- 0.2 (SEM) to 12.3 +/- 0.3 g/dL after iron replacement. Mean T-cell percentage increased from 50% +/- 3.0% to 58% +/- 3.7%. Absolute numbers of T cells were unchanged. Three children converted negative in vitro proliferative responses to Candida or tetanus antigen. Mean stimulation indexes increased for Candida (6.8 +/- 1.7 to 17.9 +/- 6.7) and tetanus (19.5 +/- 6.0 to 31.7 +/- 8.5). Nine of 16 delayed hypersensitivity skin tests were positive before and ten of ten were positive after iron therapy. The IgG and IgA levels did not change significantly, but IgM levels decreased from 181 +/- 13 to 128 +/- 5 mg/dL. We conclude that T-cell immunity is slightly impaired in pure iron deficiency and that these subtle defects can be corrected with oral iron replacement.

In vitro immunoglobulin (Ig) production was studied in two brothers with X-linked infantile agammaglobulinemia (XLA) to determine the etiology of their differing serum Ig levels. Patient 1 (P1), age 17 years, had an IgG level of 122 mg/dl, IgA undetectable, and IgM levels of 0 to 6 mg/dl while patient 2 (P2), age 14 years, had IgG level of 184 mg/dl, IgA undetectable, and IgM values of 24 to 35 mg/dl. Both boys had normal percentages of T lymphocytes and normal responses to PHA. P1 had 1% circulating B cells and P2 had no detectable circulating B cells. Both boys had identical HLA-A and HLA-B antigens and similar complete blood counts and differentials, including 8–18% monocytes. In vitro Ig synthesis was measured in pokeweed mitogen stimulated cell cultures by [35S]methionine incorporation and Ig immunoprecipitation. Neither boy was able to synthesize Ig in vitro, but only P1 had cells which suppressed Ig synthesis of control cells. T-Cell fractions from these boys showed normal helper and suppressor activity when cultured with control B cells. However, the non-T-cell fraction from P1 suppressed Ig synthesis. This suppressor effect could be eliminated by removing plastic adherent cells from P1's mononuclear cells or T-depleted fraction, suggesting monocyte suppressor cells. We conclude that the B-cell defect in XLA can be modified by secondary monocyte-mediated suppression, resulting in phenotypic variation in laboratory findings.

To assess the immune responses to specific antigen, three diphtheria and tetanus toxoid immunizations were administered to an infant girl with marked impairment of both cellular and humoral immune functions who was monitored in a gnotobiotic environment since birth. Before and after stimulation no circulating diphtheria and tetanus antitoxin could be detected. However, each immunization was followed by progressive lymphocytosis, generalized lymphadenopathy, hepatosplenomegaly and the appearance of a thymic shadow on chest X ray. Biopsies of the lymph nodes and thymus showed few lymphocytes and prominent reticular cells. During this time the proportion of T cells increased from 30 to 70%. Despite this, her lymphocytes were not stimulated when cultured in the presence of nonspecific mitogens or antigens. Helper lymphocyte function was transiently demonstrable after the second DT immunization by an in vitro immunoglobulin production assay. An additional transient leukemoid reaction occurred 2 weeks after bone marrow transplantation from a histocompatible brother. These findings support the concept that in those patients with severe combined immunodeficiency disease, with lymphadenopathy, hepatosplenomegaly, and lymphocytosis, the cellular proliferation may be the result of antigenic stimulation.

In vitro immunoglobulin (Ig) synthesis was evaluated in three young men having immunodeficiency with hyper-IgM. Patient and normal T and B cells were separated and cultured in various combinations. 35S-methionine incorporation into Ig was measured using immunoprecipitation, and Ig classes were determined by SDS-polyacrylamide gel electrophoresis with autoradiography. The patient B cells were able to produce only IgM in culture with either autologous or allogeneic T cells. Normal B cells produced IgM, G and A when cultured with normal T cells. T cells from two of the patients suppressed the Ig synthesis of normal B cells; irradiation of these T cells allowed them to provide T helper function. T cells from the third patient expressed normal T suppressor/helper activity. This implies that defective differentiation of B cells into IgG- and IgA-producing plasma cells may be a constant feature of immunodeficiency with hyper-IgM, and that excessive T suppressor activity is a variable accompanying abnormality.

We studied B and T cell function in 3 boys (20, 9, and 10 yrs) with Dysgammaglobulinemia I (Dys. I). Patients 1 and 2 are first cousins. Patient 3 is adopted. Peripheral blood mononuclear cells were separated using centrifugation on Ficoll-Hypaque gradients. T and B cells were quantitated using sheep erythrocytes and fluoresceinated anti-human immunoglobulin. Patient and normal T and B cells were separated and cultured in various combinations. Immunoglobulin (Ig) production, which requires cooperation between T and B cells, was assessed by culturing cells for 5 days with pokeweed mitogen and then determining the amount of 35S-methionine incorporated into secreted total Ig. Ig classes were determined by polyacrylamide gel electrophoresis. T and B cell percentages and numbers were normal or nearly so in all patients. Total Ig synthesis was deficient in all 3 boys. Normal B cells with normal T cells produced IgG, M and A whereas each patient's B cells with autologous or normal T cells produced only small amounts of IgM. Addition of T cells from patient 1 or 2 to normal B cells suppressed Ig synthesis; irradiation of these T cells reversed the suppression and allowed them to provide T-helper function. Patient 3 had normal T-suppressor and T-helper activity. We conclude that defective differentiation of B cells into Ig producing cells is a constant feature of Dys. I and excessive T-suppressor cell activity is a variable accompanying abnormality.

To determine the effect of iron deficiency on immune function, cell mediated immunity and immunoglobulins were evaluated in iron deficient children. Nine children 8-30 months old appearing well nourished with heights and weights 3rd to 97th percentile and arm circumferences 5.25-7″, clinically in good health but with Hgb ≥8.8gm/dl were studied. CBC, immunoglobulins, E-rosettes, and candida, tetanus and PHA stimulation as well as skin tests were performed before and after oral iron replacement. Hemoglobin increased to 10.2-13.3gm/dl with treatment. Evaluating percentage change in E-rosettes [(E2-E1)/E1 × 100]; three children increased rosetting cells; 24.5, 38.6 and 45%. Three children increased E-rosette cells 11.7 to 15.2%. In two children there was no appreciable change and one child had a decrease in E-rosettes. There were no low values of IgG but several children had increases in IgG after iron replacement (200-400mg/dl greater). Changes in delayed hypersensitivity were noted with iron therapy, but pretreatment skin tests may have contributed to these changes. Six of nine iron deficient children showed increases in E-rosettes with oral iron replacement. The presence of subtle T-cell defects in these children may help explain the increased susceptibility to severe infections in anemic children.