Restoration of immunoglobulin secretion in vitro in common variable immunodeficiency by in vivo treatment with polyethylene glycol-conjugated human recombinant interleukin-2

Abstract

Patients with common variable immunodeficiency (CVI) have decreased immunoglobulin levels resulting in frequent infections. Although previous studies have suggested that the B cell is intrinsically defective, numerous T cell deficiencies, including reduced interleukin-2 (IL-2) production, have been described. Since the addition of T cell cytokines to CVI B cells can increase Ig secretion in vitro, hypogammaglobulinemia in CVI may be due to defective T cell functions. To assess this possibility directly, we treated five CVI patients intravenously with a new biologic, human recombinant IL-2 conjugated to polyethylene glycol. Doses were 250,000 IU/m2 weekly for Weeks 1-4, 500,000 IU/m2 for Weeks 5-8, and 10(6) IU/m2 for Weeks 9-12. During and after treatment, B cells of all patients secreted 10- to 1000-fold more Ig in vitro. There was also a striking improvement in T cell helper activity since T cells of treated patients could induce 10- to 10,000-fold increases in Ig secretion by B cells from normal donors. No increase was seen in serum Igs during the study, but the anti-tetanus antibody of the IgG isotype could be detected in cell culture supernatants. Whether the effects of infused polyethylene glycol IL-2 are mediated through T or B cells, or both, is still unknown. However, these data reinforce the concept that CVI B cells may be competent, but, lacking essential T cell growth factors, in vivo maturation to Ig production does not occur.