Congenital Immune Deficiency Research Articles

Antibodies to nucleic acids in congenital immune deficiency states

The presence of antibodies to native DNA, single-stranded DNA, and double-stranded RNA was determined for 37 patients with selective IgA deficiency, 11 patients with Wiskott-Aldrich syndrome, seven patients with common variable agammaglobulinemia, 14 patients with ataxia telangiectasia, six patients with intestinal lymphangiectasia, and one patient with Nezelof syndrome. Of 37 patients with selective IgA deficiency, 11 had antibodies to at least one nucleic acid; six had antibodies to native DNA, seven had antibodies to single-stranded DNA, and four had antibodies to double-stranded RNA. The only other congenital immune deficiency disease studied in which antibodies to nucleic acids were found was the Wiskott-Aldrich syndrome; in this group three of 11 patients had antibodies to native DNA. Retrospective analysis of our patients with SLE disclosed a 2.6% prevalence of IgA deficiency, a prevalence clearly higher than in the general population. These studies provide further evidence of the association between autoimmunity and abnormalities of IgA production and suggest a relationship between thymic-derived immune regulation and IgA production.

Germ-free delivery. The initiation of management of infants with a high probability of congenital immune deficiency states

Germ-free delivery of an infant with a high probability of congenital severe combined immune deficiency disease was accomplished by cesarean section without major modification of routine medical and nursing procedures. The male sex of the infant had been determined by karyotype on amniotic fluid cells, thus the risk of being affected by an X-linked disease was established. Intensification of ordinary methods for preparation of operating area and personnel resulted in successful germ-free delivery. Highly technical equipment and specially trained people with attendant high cost were not required. The infant was placed in a sterile plastic flexible film isolator where he has been maintained in a gnotobiotic state for twelve months (to date) free of infection in spite of continued immune incompetence. With the likelihood that lesser forms of this disease may be more common than heretofore expected and with the advent of new obstetric and immunologic diagnostic techniques, sterile delivery may assume more importance in the future.

Uncertain role of cytosine arabinoside in varicella infection of compromised hosts

V A R I C E L L A zoster virus infections in compromised hosts can be serious and sometimes lethal. Complications of pr imary infection with this virus (varicella) have been noted in association with leukemia 1 and /o r steroid therapy 2 in childhood. Cytosine arabinoside (1-fl-D-arabinofuranosylcytosine, ARA-C, CA) has been shown to have activity in vitro against several D N A viruses. The drug has been used clinically in severe infections by herpes group viruses in infants or hosts impaired by malignancy, chemotherapy, or congenital immune deficiency. A total of ten patients with varicella treated with this drug have been described? -5 In these reports, the authors have concluded that the therapeutic results were favorable. Despite potential hematopoietic drug toxicity, and the absence of any controlled drug trial (or even data in comparable untreated groups), several workers 6,~ have recently stated their belief that controlled studies with this drug in varicella zoster infections would be unethical. This report summarizes our experience with cytosine a'rabinoside in

Immunological deficiency and malignant lymphoma.

Immunologkal studies suggest that Hodgkin's disease is the result of proliferation of a thymus dependent population of lymphocytes and that lymphatic leukemia is the result of a proliferation of a non-thymus-dependent population of lymphocytes. Certain congenital immune deficiency states are associated with a high incidence of malignant lymphoproliferative diseases. Such congenital diseases are overtly present in few patients with malignant lymphomas; however, evidence is adduced to show that there are physiological periods of relative immune deficiency and that these periods differ for the 2 populations of lymphocytes. The author hypothesizes that susceptible individuals are at increased risk of developing malignant lymphomas during these periods. This hypothesis helps to explain the wide difference in peak age distribution between lymphatic leukemia (the very young with acute lymphoblastic leukemia and the very old with chronic lymphocytic leukemia) and Hodgkin's disease (the adolescent and young adult).

On the existence of selenium monoxide

<h3></h3> Gene therapy is a promising alternative to conventional therapies for patients affected with congenital immune deficiencies. Although retroviral vectors are an effective means to deliver normal versions of the affected genes to the DNA of hematopoietic stem cells (HSCs), their insertion into DNA is random and may precipitate leukemic events should they insert near proto-oncogenes. A potential approach to this problem is the use of “suicide genes,” a second gene added to the therapeutic retroviral vector that can be used to eliminate cells if they cause leukemia. One candidate is the herpes simplex virus thymidine kinase (HSV-TK) gene. If patients undergoing gene therapy develop leukemia, they can be administered the prodrug ganciclovir, which will be activated by the thymidine kinase protein expressed by the transduced leukemic cells. Ganciclovir will eliminate any cells expressing HSV-TK while leaving other cells intact. However, immune-deficient patients undergoing treatment with the therapeutic retroviral vector and suicide gene can subsequently acquire herpes virus infections. These patients cannot be treated with antiviral nucleosides such as ganciclovir or acyclovir because they will kill off the corrected cells. Foscarnet, a drug used to treat ganciclovir- and acyclovir-resistant herpes infections, may be an alternative treatment for these patients. We evaluated the in vitro sensitivity of transduced TK cell lines to ganciclovir, acyclovir, and foscarnet using a 5-day cytotoxicity assay with varying concentrations of each drug. Cell lines remained near 100% viability in the presence of foscarnet while demonstrating low viability in the presence of ganciclovir and acyclovir. The ability of these cell lines to survive in the presence of foscarnet improves the therapeutic value of the suicide gene approach to gene therapy as it may provide viable treatment option for patients who acquire herpes infections.