An initial investigation of serum cytokine levels in patients with gadolinium retention (2020).
Authors: Holden T. Maecker, Stanford University Medical Center, Stanford, CA, USA.
Weiqi Wang, Stanford University Medical Center, Stanford, CA, USA.
Yael Rosenberg-Hasson, Stanford University Medical Center, Stanford, CA, USA.
Richard C. Semelka, Richard Semelka Consulting, PLLC, Chapel Hill, NC, USA.
Joseph Hickey, Hickey Wellness Center, Hilton Head, SC, USA.
Lorrin M. Koran, Stanford University Medical Center, Stanford, CA, USA.
Paper Link: https://www.scielo.br/j/rb/a/q55qtj7dsTY9sSD8HqfZykH/?lang=en
Main Theme: This case-control study investigates whether individuals with suspected Gadolinium Deposition Disease (GDD) exhibit elevated levels of pro-inflammatory and pro-fibrotic cytokines in their serum. The research explores potential correlations between specific cytokines and the manifestation of GDD symptoms.
Key Findings:
Elevated Pro-inflammatory Cytokines: This study reveals that patients meeting the proposed diagnostic criteria for GDD exhibit significantly elevated serum levels of 14 cytokines, including nine pro-inflammatory cytokines, compared to a control group (p ≤ 0.05).
"Serum levels of 14 cytokines, including nine pro-inflammatory cytokines, were statistically significantly elevated compared to controls (p ≤ 0.05)."
No Confirmation of Pro-fibrotic Cytokine Elevation: The study did not find statistically significant elevations in the hypothesized pro-fibrotic cytokines.
"Hypotheses regarding pro-fibrotic cytokines and cytokine links to specific symptoms’ intensity were not confirmed."
Potential Role of Cytokines in GDD: The authors suggest that the elevated pro-inflammatory cytokines could either indicate susceptibility to GDD or contribute to symptom development.
"The statistically significantly elevated cytokines may be markers of susceptibility to GDD or agents of symptom induction."
Chelation Treatment and Cytokine Levels: While not definitive, the study observed varied changes in cytokine levels immediately following chelation treatment with DTPA, potentially suggesting a complex interplay between gadolinium, DTPA, and the immune system.
"The reason for the cytokine level changes immediately after DTPA chelation is not clear."
Limitations: The study acknowledges limitations, including the small sample size, lack of pre-MRI cytokine data, and potential confounding factors such as co-morbidities and medications.
Important Ideas and Facts:
GDD is a recently described condition affecting individuals with normal kidney function who have undergone gadolinium-based contrast agent (GBCA)-enhanced MRI.
Symptoms of GDD can include pain, skin thickening, cognitive disturbances, headaches, and vision/hearing changes.
Previous in vitro and animal studies demonstrated that gadolinium exposure can stimulate pro-inflammatory and pro-fibrotic cytokine production.
This study provides the first in vivo evidence of cytokine abnormalities in individuals with suspected GDD.
The findings suggest a potential role for pro-inflammatory cytokines in the pathogenesis of GDD symptoms.
What is Gadolinium Deposition Disease (GDD)?
GDD is a recently described disease that has been reported in patients with normal kidney function after undergoing a contrast-enhanced Magnetic Resonance Imaging (MRI) scan. GDD symptoms, which begin unexpectedly within minutes to two months after receiving a GBCA, can include:
Cognitive impairment
Pain in the extremities
New onset, frequent headaches
Chest wall pain
Skin pain
Joint pain
Skin thickening
Skin hyperpigmentation
Bone pain
Muscle pain
Tingling sensations
Muscle twitching
Fatigue
Dry eyes
Eye pain
Diminished visual acuity
What causes GDD?
While the exact cause of GDD is not fully understood, it is believed to be associated with the retention of gadolinium (Gd), a heavy metal found in gadolinium-based contrast agents (GBCAs) used in MRI scans.
What are the symptoms of GDD?
The symptoms of GDD are varied and can include cognitive impairment, pain, skin changes, and other systemic issues. See the list of symptoms above. It is important to note that not everyone who receives a GBCA will develop GDD.
How is GDD diagnosed?
Diagnosis is currently based on clinical presentation, history of GBCA exposure, and the exclusion of other possible causes for the symptoms. Additionally, a 24-hour urine test to measure gadolinium levels may be helpful in supporting the diagnosis.
What is the role of cytokines in GDD?
Cytokines are signaling molecules that play a crucial role in the body's immune response. Research has shown that patients with GDD have significantly elevated serum levels of multiple pro-inflammatory cytokines, suggesting that inflammation may be a key factor in the development of GDD symptoms.
Are there any treatments for GDD?
There is no established cure for GDD. However, some patients have reported symptom improvement after undergoing chelation therapy with diethylene triamine penta-acetic acid (DTPA), which helps to remove gadolinium from the body. However, chelation therapy can have side effects and more research is needed to determine its long-term safety and efficacy in treating GDD.
What are the long-term implications of GDD?
The long-term implications of GDD are not yet fully known, as it is a relatively newly recognized condition. More research is needed to understand the potential long-term effects of gadolinium retention and the effectiveness of different treatment approaches.
What should I do if I suspect I may have GDD?
If you have received a GBCA and are experiencing symptoms consistent with GDD, it is important to consult with a medical professional. They can evaluate your symptoms, medical history, and determine the appropriate course of action, which may include further testing or referral to a specialist.
Glossary of Key Terms
Gadolinium Deposition Disease (GDD): A recently identified condition characterized by persistent symptoms like pain, skin changes, and cognitive impairment, potentially associated with gadolinium retention following administration of GBCAs.
Gadolinium-Based Contrast Agents (GBCAs): Chemical compounds containing gadolinium, a heavy metal, used to enhance the visibility of internal organs and tissues in MRI scans.
Cytokines: Signaling proteins produced by immune cells that regulate various immune responses, including inflammation and cell growth.
Pro-Inflammatory Cytokines: Cytokines that promote inflammation, a crucial part of the immune response but also involved in the development of various diseases when dysregulated.
Pro-Fibrotic Cytokines: Cytokines that stimulate the formation of fibrous connective tissue (fibrosis), potentially leading to tissue stiffening and organ dysfunction.
Macrocyclic GBCAs: A category of GBCAs with a more stable chemical structure, theoretically reducing the risk of gadolinium release and retention in the body.
Linear GBCAs: A category of GBCAs considered less stable than macrocyclic agents, potentially increasing the risk of gadolinium release and retention.
DTPA (Diethylenetriaminepentaacetic acid): A chelating agent that binds to heavy metals like gadolinium and helps to eliminate them from the body.
Median Fluorescence Intensity (MFI): A measure of the fluorescence signal generated by a specific cytokine in the Luminex assay, reflecting the concentration of the cytokine in the sample.
Wilcoxon Rank-Sum Test: A statistical test used to compare the distribution of two independent samples, particularly suitable for non-normally distributed data.
