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To investigate some aspects of immune function in cystic fibrosis, we measured serum immunoglobulins in 419 patients. Twenty-two per cent of the 154 patients less than 10 years old had hypogammaglobulinemia-G, whereas the older patients had normal or elevated serum immunoglobulins. A single mechanism accounting for the extraordinary prevalence of hypogammaglobulinemia in young patients with cystic fibrosis was not defined in studies of T and B-lymphocyte function in vitro or in studies of IgG metabolism in vivo. Analysis of objective clinical data, including arterial blood gases, chest roentgenograms, and bacteriologic cultures, indicated that the patients with hypogammaglobulinemia had significantly less severe lung disease than did age-matched patients with cystic fibrosis and normal or elevated IgG levels. We conclude that progression of lung disease may be due in part to a hyper-immune response.

We investigated the immune function of a patient with anergy and acquired hypogammaglobulinemia. Despite normal numbers of B cells and T4+ inducer and T5+ suppressor T cells, this patient's lymphocytes did not produce immunoglobulin, proliferate in response to soluble antigens, or generate helper factors in vitro. In addition, her T4+ T cells did not express la molecules after stimulation by soluble antigen. In mixing experiments, her T cells did not induce immunoglobulin secretion by B cells from a normal, HLA-D-identical sibling; this failure was not due to excessive suppression, since the patient's T cells did not abrogate immunoglobulin production by the normal sibling's T and B cells. Moreover, the patient's B cells secreted immunoglobulin in the presence of the sibling's T4+ cells. In contrast to the deficient inducer cells, the patient's T5+ T cells were capable of expressing suppressor-cell functions. These results indicate that immunodeficiency may occur because of a selective loss of T4+ inducer function.

Two patients with the Wiskott-Aldrich syndrome had complete donor lymphoid and hematopoietic engraftment after successful allogeneic bone-marrow transplantation. One patient had had only a temporary donor T-lymphocyte graft after a previous transplantation, for which he had been prepared with cytarabine and cyclophosphamide; the patient's own T lymphocytes returned six months later. A repeat transplant, for which the patient was prepared with anti-human thymocyte serum, total-body irradiation and procarbazine, resulted in complete donor engraftment. The second patient underwent a successful transplantation after similar preparation, except that procarbazine was omitted. At 11 and five months after transplantation both had normal hematopoiesis and no evidence of graft-versus-host disease. This treatment of the Wiskott-Aldrich syndrome may be a model for the correction of other genetically determined immune and hematologic bone-marrow disorders.