T-cell inhibitory capacity of hyperimmunoglobulins is influenced by the production process

Intravenous immunoglobulin (IVIg) preparations are widely used for anti-inflammatory therapy of autoimmune and systemic inflammatory diseases. Hyperimmunoglobulins enriched in neutralizing antibodies against viruses can, in addition to their virus-neutralizing activity, also exert immunomodulatory activity. Previously, we observed that Cytotect (R), an anti-CMV hyperimmunoglobulin, was less effective in suppressing human T-cell responses in vitro compared to Hepatect (R) CP, an anti-HBV hyperimmunoglobulin. We hypothesized that the poor immunomodulatory activity of Cytotect (R) results from treatment with beta-propiolactone during the manufacturing process. The manufacturer of these hyperimmunoglobulins has now introduced a new anti-CMV hyperimmunoglobulin, called Cytotect (R) CP, in which beta-propiolactone treatment is omitted. Here we show that Cytotect (R) CP inhibits PHA-driven T-cell proliferation and cytokine production with similar efficacy as Hepatect CP, whereas the former Cytotect (R) does not. In addition, Cytotect (R) CP inhibits allogeneic T-cell responses better than Cytotect (R). Our results advocate the use of hyperimmunoglobulins that have not been exposed to beta-propiolactone in order to benefit from their immunomodulatory properties. (C) 2014 Elsevier B.V. All rights reserved.