Johns Hopkins University School of Medicine

Author Of 1 Presentation

Biomarkers and Bioinformatics Poster Presentation

P0103 - Liothyronine treatment of MS patients alters proteins in CSF related to angiogenesis and immune function (ID 438)

Speakers
Presentation Number
P0103
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Thyroid hormones have effects on a variety of glial and immune cell populations that appear to be involved in the pathogenesis of multiple sclerosis (MS). Since tri-iodothyronine (T3) is believed to mediate the most important thyroid hormone actions, liothyronine (synthetic T3) may have the potential to induce reparative mechanisms and limit neurodegeneration in MS.

Objectives

To utilize proteomics to assess the effect of liothyronine treatment on the cerebrospinal fluid (CSF) proteome in MS.

Methods

We utilized CSF collected from 18 patients with MS enrolled in a single center trial of oral liothyronine for 24 weeks. Participants received liothyronine according to a standardized dose-titration schedule. Participants continued their maintenance MS immune therapies during the study. Eligibility criteria included euthyroid patients, 18-58 years old, 2010 McDonald MS and Expanded Disability Status Scale (EDSS) score 3.0-7.5. Main exclusion was known thyroid dysfunction. The primary outcome was safety and tolerability of liothyronine. CSF was collected at baseline and end of study (24 weeks) as an exploratory outcome for treatment response. SOMAscan platform (DNA aptamer based detection of proteins) was used to detect and quantify a panel of 1314 proteins in the CSF.

Results

Study participants had a mean age of 45.9 ± 8.8 years, F:M ratio of 7:9, relapsing disease (11/16), mean disease duration of 9 years and median EDSS of 3.5. Of the measured proteins, 46 changed (19 increased and 27 decreased) over the course of the study (p<0.05). These included proteins related to immune function such as TACI, NKp46, IgA and IgD and angiogenesis such as Cadherin-5, sTIE-1 and ANGPT2. Enrichment analyses using PANTHER and STRING databases noted that the biological processes that were over-represented included – angiogenesis and innate and adaptive immune function. Angiogenesis related proteins predominantly demonstrated an increase with liothyronine treatment while the majority of immune related proteins decreased with treatment.

Conclusions

Changes in CSF proteins involved in central nervous system immune cell function and promotion of angiogenesis were seen with a short course of liothyronine treatment in people with MS. A larger clinical trial would help determine whether these observed changes have a biological effect that is clinically meaningful.

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