Discovering novel immunological clues in small fiber neuropathy with innovative techniques

Small fiber neuropathy (SFN) is underdiagnosed and underrecognized, due to a lack of diagnostic tools. However, we now know that SFN is much more prevalent than once thought and is much more common than other inflammatory neurological disorders. Therefore, it is imperative to further research this new entity.

Over 50% of patients suffer from idiopathic SFN, i.e., the cause is still unknown. Despite multiple suggestions of association between autoimmunity with SFN, few autoantibodies or immune compounds have been described. The primary research focus of Dr. Amanda Chan, Senior Consultant at National University Hospital (NUH) and Assistant Professor at the National University of Singapore, is to identify the etiology and pathophysiology of SFN, with a focus on immunological mechanisms.

In this SelectScience^® webinar, now available on demand, Dr. Chan reviews the current literature on autoimmunity in SFN, and her journey into discovering novel autoantibodies in idiopathic SFN with the innovative Sengenics KREX™ platform, the results of which were just published in the highly impactful Annals of Neurology. By understanding more about the pathophysiology, Dr. Chan hopes to develop precision treatments for her patients with debilitating SFN symptoms.

Read on for highlights from the live Q&A session of register to watch the webinar at a time that suits you.

Studies have shown the IgG versus fibroblast growth factor receptor 3, and IgM versus trisulfated heparin disaccharide are detected in up to 20% of patients with idiopathic SFN. Would the future of this study expand into discovering other autoantibody biomarkers derived from other immunoglobulin isotopes and subtypes?

AC: That is a very important plan that we have moving forward because the proteomics studies screen for these autoantibodies, but we don't know what subgroup those antibodies belong to. There are future plans of doing ELISA or other cell-based assays in order to find out what antibody subgroup these autoantibodies belong to. I think it's a very important question to help us to find out what the pathophysiology of idiopathic SFN is.

What would be the role of MX1 autoantibodies in iSFN patients? If its presence suggests dysfunctional immunity, anti-MX1 may be a potential biomarker to guide treatments such as immune system modulating therapies.

AC: MX1 autoantibodies have been described in some papers, showing that they interact with TRPC6 receptors, the transient receptor canonical protein, which is a transmembrane protein. And that's been found to be overexcited in patients with chronic back pain, and also in some mice models as well. I expect we still need to prove this.

What I predict is that patients with idiopathic small fiber neuropathy could have some antibodies attacking MX1, which further alters the TRPC6 activity, possibly causing hyperexcitability and hence pain. We are also working on this further to delineate the mechanism behind this with in vitro models and also electrophysiological tests.

Can you tell us what you're hoping for the future of your work?

AC: I'm hoping that we can develop a panel that will help us in the diagnosis of SFN, help us in the treatment of SFN to develop, or even just choose, more precise treatments for our patients. My patients count on me to give them an answer because many of their symptoms are quite debilitating. I have to say that I'm doing all this mainly for my patients and I hope I can offer them some kind of solution for their problems.

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