Analysis of a family containing three members with common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID), a diverse immunodeficiency syndrome characterized by low immune globulin levels and recurrent infections, has been observed in families with the HLA A1 B8 DR3 haplotype. METHODS: We report a two-generation family with three members affected by CVID. Immunoglobulin levels, antibody titers, lymphocyte marker analyses, T cell proliferation assays, and HLA typing were performed on the affected family members. RESULTS: Studies of the affected patients revealed low levels of immunoglobulin G and A; normal tetanus, rubella and rubeola antibody titers; low B cell numbers; normal T cell numbers; normal CD4/CD8 ratios and normal lymphocyte proliferation studies. HLA typing did not reveal the HLA A1 B8 DR3 haplotype previously associated with familial CVID. CONCLUSION: We report a family with a unique presentation of CVID involving possible genetic inheritance other than the HLA A1 B8 DR3 haplotype and possessing lymphocyte characteristics distinct from those usually seen in sporadic CVID.

Circulating thymulin and thymosin-alpha 1 activity in pediatric acquired immune deficiency syndrome: in vivo and in vitro studies.

Twenty-five children with acquired immune deficiency syndrome (AIDS) or AIDS-related complex had a characteristic pattern of T cell deficiency. Abnormally low plasma thymulin levels preceded the development of peripheral blood T cell abnormalities. In contrast to patients with congenital T cell deficiencies, our patients had elevated serum levels of thymosin-alpha 1. Treatment with thymosin fraction 5 in three children with AIDS resulted in only transient clinical and immunologic improvement.

Bacterial infection in the acquired immunodeficiency syndrome of children.

We have followed 46 children with acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related complex. Twenty-six patients had at least one episode of serious bacterial infection. Twenty-seven episodes of sepsis were documented in 21 patients. Soft tissue infection was common in both the presence and the absence of documented bacteremia. Urinary tract infection commonly presented as worsening diarrhea in the absence of sepsis. Organisms commonly isolated included Streptococcus pneumoniae, Haemophilus influenzae and Salmonella sp. Staphylococcal infection accompanied episodes of cellulitis/abscess. Escherichia coli commonly caused urinary tract infection in the absence of sepsis. Enteric and nosocomial sepsis was limited to hospitalized, instrumented patients or to individuals who had received prior antibiotic therapy as outpatients. We conclude that bacterial infection causes serious morbidity in acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related complex and may be further evidence for altered humoral immunity in the disorder.

Acquired immunodeficiency with reversed T4/T8 ratios in infants born to promiscuous and drug-addicted mothers.

A new syndrome of acquired immunodeficiency has been identified in seven children who were small for gestational age at birth and subsequently have exhibited failure to thrive, lymphadenopathy, parotitis, hepatosplenomegaly, interstitial pneumonia, and recurrent infections. All have a profound cell-mediated immunodeficiency with reversed T4/T8 ratios. Six are hypergammaglobulinemic and one has low IgG levels. The mothers of five of the seven children are sexually promiscuous and/or drug addicts. Three mothers have an immunodeficiency similar to that found in their infants. One of them died at age 33 years with a diagnosis of acquired immunodeficiency syndrome. In five of the children and in three of their mothers, there is evidence of a persistent Epstein-Barr virus (EBV) infection. We speculate that a perinatal or in utero transmission of EBV can induce an "infectious immunodeficiency." The clinical, histopathologic, and immunologic features resemble those described in adult homosexuals and drug addicts.

Induction of immunoglobulin synthesis in corticosteroid-treated blood lymphocytes of a patient with acquired agammaglobulinemia.

Coculture experiments between lymphocytes of a 17-year-old immunodeficient male, DL, and a group of normal subjects, assaying pokeweed mitogen (PWM)-stimulated Ig secretion as a measure of B-cell function, revealed immunoregulatory abnormalities. Initial studies disclosed that DL had corticosteroid-sensitive T suppressor (Ts) cells capable of blocking Ig secretion by both HLA-identical and HLA-nonidentical cells in coculture. Cocultures of DL's peripheral blood mononuclear cells could be induced to secrete Ig in large amounts after certain maneuvers--the most informative of which involved mixing prednisolone-treated DL mononuclear cells with any normal T lymphocytes except those from DL himself. When these same experimental manipulations were performed individually, i.e., prednisolone treatment of cultured DL cells to remove Ts activity, or mixing equal numbers of normal T cells with untreated DL mononuclear cells, Ig was not produced. The data indicated that the T-cell abnormalities in DL included an excess of Ts cells and a deficiency to T helper (Th) cells. When repeat studies were performed later in the clinical course, during which interval a number of clinical interventions were attempted, it was found that the patient's cells were no longer corticosteroid sensitive and, further, they suppressed only HLA-identical cells.

Antihelper T cell autoantibody in acquired agammaglobulinemia.

A patient with acquired agammaglobulinemia had an antihelper T cell factor that was identified as an immunoglobulin of the IgG class. The factor specifically bound to the TH2- T cell subset and, in the presence of complement, abolished the helper effect of normal T cells. The antihelper T cell antibody preceded by several years the appearance of suppressor TH2+Ia+ T cells, at which time the clinical course rapidly deteriorated. Plasmapheresis resulted in lymphocytosis and reappearance of a functionally intact helper T cell population. It did not affect the suppressor cells. Conversely, total thymectomy resulted in a temporary disappearance of the TH2+Ia+ suppressor cells, but did not decrease the levels of the autoantibody to helper T cells. Neither of these treatments reversed the state of agammaglobulinemia.

In vivo and in vitro effects of thymosin and adenosine deaminase on adenosine-deaminase-deficient lymphocytes.

Two siblings with adenosine deaminase deficiency were studied before and during "enzyme replacement" therapy (partial exchange transfusions with normal red cells containing the missing enzyme). The younger sib showed improvement of immunologic function during red-cell therapy alone, whereas in the older sib this improvement occurred only when the transfusions were supplemented by thymosin injections. Their clinical courses correlated with in vitro findings: lymphocytes from the younger sib differentiated to T-cell-rosette-forming cells upon addition of adenosine deaminase alone; lymphocytes from the older sibling required supplemental thymosin to form these cells. Thymic factors appear to influence the response to transfusion therapy in some patients deficient in adenosine deaminase, and supplementation of red-cell transfusion with thymic factors may be required.