Molecular analysis for patients with IL-12 receptor β1 deficiency

Autosomal recessive interleukin-12 receptor β1 (IL-12Rβ1) deficiency has been described as the most common cause of Mendelian susceptibility to mycobacterial disease (MSMD), characterized by clinical disease due to weakly virulent mycobacteria such as Bacille Calmette-Guérin (BCG) vaccines and environmental mycobacteria (EM) in children who are normally resistant to most infectious agents. Here, we report the cases of five patients with mycobacterial infection, including one with systemic lupus erythematosus (SLE). Blood samples from patients and healthy controls were activated in vitro with BCG, BCG+IL-12, and BCG+IFN-γ. The results showed reduced or no production of IFN-γ after IL-12 stimulation in all samples. IL-12Rβ1 expression on the cell surface was negligible or absent. Genetic analysis showed five novel mutations.