Immunosuppression in elderly recipients has been underappreciated in clinical trials. Here, we assessed age-specific effects of the calcineurin inhibitor Tacrolimus (TAC) in a murine transplant model and assessed its clinical relevance on human T-cells.
Old recipient mice exhibited prolonged skin graft survival when compared to young animals following TAC administration. More importantly, half of the TAC dose was sufficient in old mice to achieve comparable systemic trough levels. TAC administration was able to reduce pro-inflammatory IFN-γ cytokine production and promote IL-10 production in old CD4+ T-cells. In addition, TAC administration decreased IL-2 secretion in old CD4+ T-cells more effectively while inhibiting the proliferation of CD4+ T-cells in old mice. Both, TAC treated murine and human CD4+ T-cells demonstrated an age-specific suppression of intracellular calcineurin levels and Ca2+-influx, two critical pathways in T-cell activation. Of note, depletion of CD8+ T-cells did not alter allograft survival outcome in old TAC treated mice, suggesting that TAC age-specific effects were mainly CD4+ T-cell mediated.
Collectively, our study demonstrates age-specific immunosuppressive capacities of TAC that are CD4+ T-cell mediated. The suppression of calcineurin levels and Ca2+-influx in both, old murine and human T-cells emphasizes on the clinical relevance of age-specific effects when utilizing TAC.
Objective
To review cases and increase awareness in clinicians treating
patients who may be taking biotin.
Methods
We describe the presentation and workup of a woman with secondary
progressive multiple sclerosis on high dose biotin with laboratory studies
suggestive of thyrotoxicosis.
Results
Plasma samples showed laboratory evidence of elevated thyroid hormone
levels with elevated free thyroxine >7.8 ng/dl (reference interval
(RI) 0.9-1.7 ng/dl) and decreased thyroid stimulating hormone <0.02
uIU/ml (RI 0.50-5.70 uIU/ml). Laboratory values normalized when biotin was
withheld prior to repeat testing.
Conclusions
Our case report demonstrates that ingestion of high dose biotin in
multiple sclerosis patients can cause interference with laboratory
assessment of thyroid function. This interference causes laboratory values
suggestive of thyrotoxicosis and can lead to unnecessary evaluation.
Clinicians should be aware of the risk of laboratory interference in this
patient demographic.
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