IMMUNOLOGICAL EFFECTS OF LOW-DOSE POLYETHYLENE GLYCOL-CONJUGATED RECOMBINANT HUMAN INTERLEUKIN-2 IN COMMON VARIABLE IMMUNODEFICIENCY

Children or adults with the primary immunodeficiency disease, common v ariable immunodeficiency (CVI), have abnormally low levels of at least two of the three serum Ig isotypes. Although there appear to be intri nsic B cell defects, many have poor T cell proliferation and deficient secretion of IL-2, IL-4, IL-5 interferon-gamma, and B cell differenti ation factor, Because the addition of various T cell factors can enhan ce Ig secretion in vitro in CVI, we have hypothesized that the B cells in this disease may be defective because they lack appropriate cytoki nes, Because IL-2 can promote Ig secretion in vitro as well as bypass T cell activation deficits, we are investigating the in vivo effects o f recombinant IL-2 using a new biologic, polyethylene glycol-conjugate d recombinant IL-2 (PEG-IL-2). In these studies, CVI patients were tre ated 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 si gnals. During PEG-IL-2 treatment, four of five patients produced detec table 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.