INTERLEUKIN-12 DEFICIENCY ASSOCIATED WITH RECURRENT INFECTIONS

A 3-yr-old female patient exhibited interleukin 12 (IL-12) deficiency that was associated with recurrent episodes of pneumococcal pneumonia with sepsis and other infections in the absence of fevers. The patient 's peripheral blood mononuclear cells (PBMCs) exhibited normal prolife rative responses to antigens, Immune responses, including in vivo prod uction of antibodies to diphtheria, tetanus, or pneumococcal antigens, were normal. Ig levels and B cell and T cell phenotypes were also nor mal, In contrast, IL-12 p70 heterodimer production was undetectable by using supernatants of the patient's stimulated PBMCs when compared wi th control cells treated similarly. Although present, interferon gamma (IFN-gamma) was reduced, The addition of recombinant IFN-gamma to con trol cells enhanced the production of IL-12 by up to sixfold, By contr ast, IL-12 was undetectable in supernatants of the patient's cells in the presence of recombinant IFN-gamma, IL-12 p40 subunit mRNA by using the patient's PBMCs after stimulation with Staphylococcus aureus Cowa n strain 1 or lipopolysaccharide was also undetectable by reverse tran scription-PCR when compared with control cells. Production of IL-2, IL -6, tumor necrosis factor alpha, or IFN-gamma of the patient's PBMCs a fter appropriate stimulation was observed. This patient has either a d efect in Staphylococcus aureus Cowan strain 1-lipopolysaccharide- or s taphylococcal enterotoxin A-induced signaling pathways for the activat ion of IL-12 p40 gene expression, or an abnormality in the IL-12 p40 g ene itself.