Paper of the Month - Dr Judith Greer

12 Jul 2017

Since the paper was published on 8 May it’s had 320 views and 40 downloads (according to the journal website).

This paper is significant, as it suggests that autoimmune disease can spread from the thyroid to the central nervous system (CNS). It’s been known for well over 100 years that people who

Dr Judith Greer

have autoimmune thyroid disease (AITD) can sometimes develop disease in the CNS, but it has usually been thought that this caused by imbalances in the thyroid hormones, rather than anything else. Sometimes, once the thyroid hormone levels are restored to normal, the neurological symptoms disappear. But not always….

We’ve studied 44 patients with co-existing AITD and autoimmune CNS demyelinating disease (mostly patients with multiple sclerosis (MS; n=40)), and found that the pattern of CNS disease and clinical symptoms is very similar in all these patients, with major involvement of the spinal cord. The pattern of human leukocyte antigen (HLA) genes expressed by the patients with co-existing AITD and MS was significantly different to what is seen in patients with MS alone, suggesting that the pathogenic mechanism is different. However, the particular type of thyroid disease also made a difference for this, and the most interesting subgroup in this study were patients who had hyperthyroidism (Grave’s disease). In the majority of cases, Grave’s disease developed prior to CNS disease. Grave’s disease is characterized by pathogenic autoantibodies specific for the thyroid-stimulating hormone receptor (TSHR). Interestingly, there is a related protein, LGR4, which is highly expressed in the spinal cord. We showed in this study that patients with co-existing MS and Grave’s disease have high levels of both T cells and antibodies specific for both TSHR and LGR4, whereas patients with MS alone show no T cell or antibody reactivity to either of these proteins, suggesting that the autoimmune reactivity directed against the TSHR has spread to target LGR4 in the spinal cord. We suggest that spreading of autoreactivity from the thyroid to related antigens in the spinal cord might represent a novel mechanism for the development of autoimmune demyelinating disease in the CNS. 

Greer, J. M., Broadley, S., & Pender, M. P. (2017). Reactivity to Novel Autoantigens in Patients with Coexisting Central Nervous System Demyelinating Disease and Autoimmune Thyroid Disease. Frontiers in immunology, 8, 514. doi:10.3389/fimmu.2017.00514