Abstract

ObjectiveTo determine whether individuals with proposed gadolinium deposition disease (GDD) have elevated serum levels of pro-inflammatory and pro-fibrotic cytokines, and whether specific cytokines are correlated with certain symptoms.Materials and MethodsTwenty-four participants recruited between May 2016 and June 2017 met GDD diagnostic criteria. The 64 control subjects provided serum samples before prophylactic flu vaccination. Serum cytokine levels were obtained with Luminex serum cytokine assay using eBiosciences/Affymetrix human 62-plex kits. Wilcoxon rank-sum tests were performed to assess the difference between the median fluorescence intensity values for the participants and the control group. Generalized linear models were built to evaluate the association between each cytokine of interest and selected participant symptoms.ResultsSerum levels of 14 cytokines, including nine pro-inflammatory cytokines, were statistically significantly elevated compared to controls (p ≤ 0.05). Hypotheses regarding pro-fibrotic cytokines and cytokine links to specific symptoms' intensity were not confirmed.ConclusionThe statistically significantly elevated cytokines may be markers of susceptibility to GDD or agents of symptom induction. These findings suggest that individuals developing symptoms characteristic of GDD after a contrast-assisted magnetic resonance imaging should be studied to investigate whether gadolinium retention and elevated cytokines may be related to their symptoms.

Highlights

  • A recently described disease termed gadolinium deposition disease (GDD) has been reported in patients with normal kidney function after magnetic resonance imaging (MRI) enhanced by gadolinium-based contrast agents (GBCAs)(1)

  • The conditions/supplements more often lowered than raised cytokine levels; conditions/ supplements could have raised tumor necrosis factor-α (TNF-α) levels in four participants, but lowered the levels in seven; and, they could have raised the IL-6 level in one participant, but lowered the level in eight

  • We intentionally used a multiplex assay to assess a large battery of cytokines in order to discover possible changes beyond those we hypothesized, which hypothesized changes were based on reported GDD symptoms and on the findings from the in vitro and animal studies[11,13,19]

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Summary

Introduction

A recently described disease termed gadolinium deposition disease (GDD) has been reported in patients with normal kidney function after magnetic resonance imaging (MRI) enhanced by gadolinium-based contrast agents (GBCAs)(1). Gd retention in patients with normal renal function has been reported, albeit without concomitant investigation for retention-associated symptoms, in bone[3], skin[4], cerebral spinal fluid[5], and brain[6,7]. We report the first study of in vivo cytokine serum levels in individuals meeting the proposed diagnostic criteria for GDD. Based on in vitro and animal studies of Gd effects on cytokine expression, we hypothesized that serum levels of pro-inflammatory and pro-fibrotic cytokines would be abnormally elevated and associated with specific GDD symptoms, as detailed below

Methods
Results
Conclusion

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