Developing and improving assays to detect autoantibodies in well phenotyped small fiber neuropathy and fibromyalgia syndrome patients

Thesis

Small Fiber Neuropathy (SFN) is one of the most cryptogenic etiologies of chronic neuropathic pain and over 40% are said to idiopathic. Recently, Autoantibodies (AAbs) against specific targets have been identified in SFN including those against FGFR3, Plexin D1, TS-HDS, and MX1. More recently, FGFR3 AAbs were found in Fibromyalgia Syndrome (FMS) patients as well, a chronic pain disorder wherein some patients also have small fiber pathology. Assays have been developed to detect these autoantibodies, like Enzyme-Linked Immunosorbent Assays (ELISAs) and Cell-Based Assays (CBAs). This Master’s thesis has used a cohort of 72 well-phenotyped SFN patients and 53 FMS patients to detect AAbs against intracellular FGFR3, Plexin D1, and MX1. In terms of assays, ELISAs, CBAs, and a novel concept of “carry-on” CBAs were developed. The “carry-on” CBA expressed the intracellular epitope of FGFR3 outside the cell and the same concept was used for full-length intracellular MX1. The carry-on CBA found 12.5% seropositivity for anti-intracellular FGFR3 IgG in the SFN patient cohort and 13.2% seropositivity in the FMS patient cohort. Lower rates of 6.4% and 3.8% were observed in the ELISA for SFN and FMS patient cohorts respectively. In both cohorts, 0% seropositivity was found for anti-MX1 IgG using the “carry-on” CBA and 0% seropositivity was found for anti-Plexin D1 IgG using the standard CBA. When associated with phenotypes, the significant differences observed in SFN patients seropositive for anti-intracellular FGFR3 were that their symptoms were less chronic (less than 5 years, p = 0.0238) and there were fewer seropositive patients with tingling pain that in seronegative patients (p = 0.0257). In FMS patients, the only significant difference was that the duration of symptoms was shorter for seropositive patients than seronegative patients (p = 0.0113). Thus, a clinically distinct group of SFN and FMS patients were found who are anti-intracellular FGFR3 IgG seropositive with a shorter duration of chronic pain symptoms.

Authors: Singh, E

• DOI: 10.5287/ora-2abyxyyxg
• Type of award: MSc by Research
• Level of award: Masters
• Awarding institution: University of Oxford
• Language: English