Common variable hypogammaglobulinemia, recurrent Pneumocystis carinii pneumonia on intravenous gamma-globulin therapy, and natural killer deficiency

Abstract

A toddler with common variable hypoimmunoglobulinemia (CVH), inflammatory bowel disease, and recurrent Pneumocystis carinii pneumonia (PCP) on intravenous gammaglobulin (IVIG) replacement was evaluated for a combined cellular immunodeficiency. He had a normal number of circulating T-cells, natural killer (NK) cells, T-cell subset percentages, and his peripheral blood mononuclear (PBM)-derived B-cell number was low. PBM mitogen blastogenesis and mixed lymphocyte reaction (MLR) were normal. MLR activated T-cells expressed class I and II MHC antigens, interleukin 2 (IL-2), and B-cell growth factor (IL-5)-related receptors. The patient's T-cells induced control B-cell maturation with pokeweed mitogen (PWM-PC), and did not suppress PWM-PC production by allogeneic PBM. Bone marrow (BM) CD19+ B-cell number varied between 10 and 44% of all PBM, and the BM B-cell-enriched fraction failed to differentiate to PWM-PC with autologous or allogeneic T-cell help. The NK activity assayed using K562 target cells was deficient, 9.2 x 7.7% (6.9-9.2%) pt, control 35.9 x 35.8% (16.3-67.2% +/- 12.8). In the presence of interferon-alpha, 800 U/ml, the patient's NK activity increased to 17.2 x 14.9% (12.6-17.2%), control 35.9 x 51.0% (36.5-72.3% +/- 12.0). The patient's cell-mediated lympholysis of HLA nonidentical, allogeneic stimulators was normal. Maintaining trough serum IgG levels above 500 mg/dl was required to suppress recurrent PCP. This functional NK deficiency may be relevant to the development of recurrent PCP in IVIG-treated CVH patients.