Treatment of disseminated mycobacterial infection with high-dose IFN-γ in a patient with IL-12Rβ1 deficiency

Abstract

IFN-γ has been used in the treatment of IL-12Rβ1 deficiency patients with disseminated BCG infection (BCGosis), but the optimal dose to reach efficacy is not clear. We used IFN-γ in the treatment of a 2.7-year-old patient with IL-12Rβ1 deficiency and refractory BCG-osis. IFNγ was started at a dose of 50 μg/m² 3 times per week. The dose was upgraded to 100 mcg/m² after 3 months, then to 200 mcg/m² 6 months afterwards. Serum mycobactericidal activity and lymphocytes number and function were evaluated throughout the study. There was no clinical response to IFN-γ with 50 or 100 μg/m² doses. However, there was some response to the 200 μg/m² dose with no additional adverse effects. The serum mycobactericidal activity was not significantly different during the whole treatment period. Lymphocytes proliferation in response to PHA was significantly higher after 3 months of using the highest dose as compared to the lowest dose. The tuberculin skin test reaction remained persistently negative. We conclude that in a patient with IL-12Rβ1 deficiency, IFN-γ at a dose of 200 μg/m², but not at lower dosages, was found to have a noticeable clinical effect with no additional adverse effects.

Figure 1

Time line of the patient's course. Above are the changes in medications and below are the changes in clinical condition from the beginning of IFN-γ introductions till the patients' death 15 months later.

Figure 2

The percent increase in T cell proliferation stimulated with PHA and IL2 in control and the three samples from the patient: (S1) before treatment, (S2) 6 months after treatment (S3) 12 months after treatment. The percent increase in Sample, (S3) stimulation with PHA was significantly higher than the response before treatment (S1) (P = .02), while no significant difference with IL2.