Gene therapy is a promising treatment option for monogenic diseases, but success has been seen in only a handful of studies thus far. We now document successful reconstitution of immune function in a child with the adenosine deaminase (ADA)-deficient form of severe combined immunodeficiency (SCID) following hematopoietic stem cell (HSC) gene therapy. An ADA-SCID child who showed a poor response to PEG-ADA enzyme replacement was enrolled into the clinical study. Following cessation of enzyme replacement therapy, autologous CD34(+) HSCs were transduced with an ADA-expressing gammaretroviral vector. Gene-modified cells were reinfused following one dose of preconditioning chemotherapy. Two years after the procedure, immunological and biochemical correction has been maintained with progressive increase in lymphocyte numbers, reinitiation of thymopoiesis, and systemic detoxification of ADA metabolites. Sustained vector marking with detection of polyclonal vector integration sites in multiple cell lineages and detection of ADA activity in red blood cells suggests transduction of early hematopoietic progenitors. No serious side effects were seen either as a result of the conditioning procedure or due to retroviral insertion. Gene therapy is an effective treatment option for the treatment of ADA-SCID.

Immune responses in 24 children with acute measles (AM) were compared with those in 20 children who had chronic pulmonary complications (CPMC) following measles. The immuno-suppressive effects of acute measles were extensive: total white cells were reduced and this reduction was accounted for entirely by lymphopenia which was equally expressed among the major lymphocyte sub-populations studied; the function of ‘T’ cells, assessed by radio-isotope incorporation into phytohaemagglutin (PHA) transformed lymphocytes and delayed skin hypersensitivity (DHR) to dinitrochlorobenzene (DNCB), was depressed. Serum IgA was reduced in AM patients. In contrast there was a relative sparing of the measured indices of immunity in patients with chronic post-measles chest disease, with the major defect being an impaired DHR to DNCB. There were minor alterations of complement components in both groups of patients.

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