Fluctuations in Quality of Life and Immune Responses During Intravenous Immunoglobulin Infusion Cycles

Abstract Despite adequate infection prophylaxis, variation in self-reported quality of life (QOL) throughout the intravenous immunoglobulin (IVIG) infusion cycle is a widely reported but infrequently studied phenomenon. To better understand this phenomenon, immunodeficiency subjects receiving replacement doses of IVIG were studied over 3 infusion cycles. Questionnaire data from 6 time points spread over 3 IVIG infusions cycles (infusion day and 7 days after each infusion) was collected in conjunction with monitoring the blood for number of regulatory T-cells (Treg) and levels of 40 secreted analytes: primarily cytokines and chemokines. At day 7, self-reported well-being increased, and self-reported fatigue decreased, reflecting an overall improvement in QOL 7 days after infusion. Over the same period, percentage of Treg cells in the blood increased (p<0.01). Multiple inflammatory chemokine and cytokine levels increased in the blood by 1 hour after infusion (CCL4 (MIP-1b), CCL3 (MIP-1a), CCL2 (MCP-1), TNF-α, granzyme B, IL-10, IL-1RA, IL-8, IL-6, GM-CSF, and IFN-γ). The largest changes occurred in subjects initiated on IVIG during the study. A significant decrease in IL-25 (IL-17E) following infusion was seen in a majority of intervals among subjects already receiving regular infusions prior to study entry. These findings confirm IVIG “wear off” and provide a basis for the phenomenon. Secondary findings including differences between IVIG-experienced and IVIG-naïve subjects and the novel finding of suppression of IL-25 levels in the blood following IVIG are identified as novel immunomodulatory aspects of IVIG infusion in immunodeficient patients worthy of further exploration.