Immunologic Effects of Low-Dose Polyethylene Glycol-Conjugated Recombinant Human Interleukin-2 in Common Variable Immunodeficiency

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Abstract
Children or adults with the primary immunodeficiency disease, common variable immunodeficiency (CVI), have abnormally low levels of at least two of the three serum Ig isotypes. Although there appear to be intrinsic B cell defects, many have poor T cell proliferation and deficient secretion of IL-2, IL-4, IL-5 interferon-γ, and B cell differentiation factor. Because the addition of various T cell factors can enhance Ig secretion in vitro in CVI, we have hypothesized that the B cells in this disease may be defective because they lack appropriate cytokines. Because IL-2 can promote Ig secretion in vitro as well as bypass T cell activation deficits, we are investigating the in vivo effects of recombinant IL-2 using a new biologic, polyethylene glycol-conjugated recombinant IL-2 (PEG-IL-2). In these studies, CVI patients were treated with weekly subcutaneous injections of PEG-IL-2. After 12 weeks, each patient had enhanced T cell proliferation, normal IL-2 production, boosted BCDF secretion, and B cells responsive to differentiation signals. During PEG-IL-2 treatment, four of five patients produced detectable serum antibody to keyhole limpet hemocyanin. These data suggest that CVI, which has the phenotype of B cell deficiency, may be caused by a lack of appropriate T cell signals for B cell maturation.